Supplementary Data TMAO Microbiome R1

BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s) Gut

Content for Supplementary Data Tables

Tables Page Annotation guide for taxonomic features. 1 Supplementary Data 1a. Microbial associations with TMAO, and intakes 7 of choline and red meat. Supplementary Data 1b. Microbial associations with TMAO in 8 15 sensitivity analysis models. Supplementary Data 2a. Associations of intakes of choline and red meat, 21 or other TMAO precursors with TMAO levels, stratified by TMAO- associated abundant species, in full models and additionally adjusted for other TMAO precursors or TMAO predicting species. Supplementary Data 2b. Associations of intakes of choline and red meat, 34 or other TMAO precursors with TMAO levels, stratified by TMAO- producer status, additionally adjusted for other TMAO precursors. Supplementary Data 2c. Associations of intakes of choline and red meat, 37 or other TMAO precursors with TMAO levels, stratified by TMAO- producer status, in 6 different sensitivity analysis models. Supplementary Data 2d. Associations of intakes of red meat with HDLC 39 and HBA1c levels, stratified by TMAO-producer status or TMAO- associated abundant species. Supplementary Data 3a. Association of DNA gene clusters within 40 TMAO-associated species with plasma TMAO levels, and intakes of choline and red meat. Supplementary Data 3b. Association of transcriptions of gene clusters 46 (RNA/DNA ratio) within TMAO-associated species with plasma TMAO levels, and intakes of choline and red meat. Supplementary Data 4a. Association of DNA enzyme within TMAO- 62 associated species with plasma TMAO levels, and intakes of choline and red meat. Supplementary Data 4b. Association of transcriptions of enzymes 64 (RNA/DNA ratio) within TMAO-associated species with plasma TMAO levels, and intakes of choline and red meat. Supplementary Data 5a. Association of functional pathways 75 (metagenomics) within TMAO-associated species with plasma TMAO levels, and intakes of choline and red meat. Supplementary Data 5b. Association of transcriptions of pathways 77 (RNA/DNA ratio) within TMAO-associated species with plasma TMAO levels, and intakes of choline and red meat.

Li J, et al. Gut 2021;0:1–10. doi: 10.1136/gutjnl-2020-322473 BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s) Gut

Annotation Annotation guide for taxonomic features. Taxonomic label Taxonomic type Kingdom Phylum Class Order Family Genus Species Strain gcf_000173975 strain bacteria firmicutes clostridia clostridiales eubacteriaceae eubacterium eubacterium_hallii gcf_000173975 eubacterium_hallii species bacteria firmicutes clostridia clostridiales eubacteriaceae eubacterium eubacterium_hallii gcf_000210575 strain bacteria bacteroidetes bacteroidia bacteroidales rikenellaceae alistipes alistipes_shahii gcf_000210575 alistipes_shahii species bacteria bacteroidetes bacteroidia bacteroidales rikenellaceae alistipes alistipes_shahii eggerthella_unclassified species bacteria actinobacteria actinobacteria coriobacteriales coriobacteriaceae eggerthella eggerthella_unclassified clostridium_clostridioforme species bacteria firmicutes clostridia clostridiales clostridiaceae clostridium clostridium_clostridioforme gcf_000225345 strain bacteria firmicutes clostridia clostridiales lachnospiraceae roseburia roseburia_hominis gcf_000225345 roseburia_hominis species bacteria firmicutes clostridia clostridiales lachnospiraceae roseburia roseburia_hominis gcf_000155435 strain bacteria firmicutes clostridia clostridiales clostridiales_noname clostridiales_noname clostridiales_bacterium_1_7_47faa gcf_000155435 clostridiales_bacterium_1_7_47faa species bacteria firmicutes clostridia clostridiales clostridiales_noname clostridiales_noname clostridiales_bacterium_1_7_47faa gcf_000233455 strain bacteria firmicutes clostridia clostridiales clostridiaceae clostridium clostridium_citroniae gcf_000233455 clostridium_citroniae species bacteria firmicutes clostridia clostridiales clostridiaceae clostridium clostridium_citroniae gcf_000242195 strain bacteria firmicutes erysipelotrichia erysipelotrichales erysipelotrichaceae erysipelotrichaceae_noname erysipelotrichaceae_bacterium_21_3 gcf_000242195 erysipelotrichaceae_bacterium_21_3 species bacteria firmicutes erysipelotrichia erysipelotrichales erysipelotrichaceae erysipelotrichaceae_noname erysipelotrichaceae_bacterium_21_3 gcf_000156035 strain bacteria firmicutes clostridia clostridiales clostridiaceae clostridium clostridium_nexile gcf_000156035 clostridium_nexile species bacteria firmicutes clostridia clostridiales clostridiaceae clostridium clostridium_nexile sutterellaceae_unclassified genus bacteria proteobacteria betaproteobacteria burkholderiales sutterellaceae sutterellaceae_unclassified gcf_000156655 strain bacteria firmicutes erysipelotrichia erysipelotrichales erysipelotrichaceae erysipelotrichaceae_noname eubacterium_biforme gcf_000156655 eubacterium_biforme species bacteria firmicutes erysipelotrichia erysipelotrichales erysipelotrichaceae erysipelotrichaceae_noname eubacterium_biforme clostridium_clostridioforme_unclassified strain bacteria firmicutes clostridia clostridiales clostridiaceae clostridium clostridium_clostridioforme clostridium_clostridioforme_unclassified eggerthella genus bacteria actinobacteria actinobacteria coriobacteriales coriobacteriaceae eggerthella burkholderiales order bacteria proteobacteria betaproteobacteria burkholderiales gcf_000166035 strain bacteria firmicutes clostridia clostridiales ruminococcaceae faecalibacterium faecalibacterium_prausnitzii gcf_000166035 betaproteobacteria class bacteria proteobacteria betaproteobacteria sutterellaceae family bacteria proteobacteria betaproteobacteria burkholderiales sutterellaceae clostridium_hathewayi species bacteria firmicutes clostridia clostridiales clostridiaceae clostridium clostridium_hathewayi bacteroides_uniformis species bacteria bacteroidetes bacteroidia bacteroidales bacteroidaceae bacteroides bacteroides_uniformis gcf_000158075 strain bacteria firmicutes clostridia clostridiales clostridiaceae clostridium clostridium_asparagiforme gcf_000158075 clostridium_asparagiforme species bacteria firmicutes clostridia clostridiales clostridiaceae clostridium clostridium_asparagiforme gcf_000218405 strain bacteria firmicutes clostridia clostridiales lachnospiraceae lachnospiraceae_noname lachnospiraceae_bacterium_3_1_57faa_ct1 gcf_000218405 lachnospiraceae_bacterium_3_1_57faa_ct1 species bacteria firmicutes clostridia clostridiales lachnospiraceae lachnospiraceae_noname lachnospiraceae_bacterium_3_1_57faa_ct1 clostridium_hathewayi_unclassified strain bacteria firmicutes clostridia clostridiales clostridiaceae clostridium clostridium_hathewayi clostridium_hathewayi_unclassified clostridium_symbiosum_unclassified strain bacteria firmicutes clostridia clostridiales clostridiaceae clostridium clostridium_symbiosum clostridium_symbiosum_unclassified clostridium_symbiosum species bacteria firmicutes clostridia clostridiales clostridiaceae clostridium clostridium_symbiosum gcf_000172175 strain bacteria bacteroidetes bacteroidia bacteroidales bacteroidaceae bacteroides bacteroides_intestinalis gcf_000172175 bacteroides_intestinalis species bacteria bacteroidetes bacteroidia bacteroidales bacteroidaceae bacteroides bacteroides_intestinalis clostridiales_noname genus bacteria firmicutes clostridia clostridiales clostridiales_noname clostridiales_noname lactococcus_lactis_unclassified strain bacteria firmicutes bacilli lactobacillales streptococcaceae lactococcus lactococcus_lactis lactococcus_lactis_unclassified lactococcus_lactis species bacteria firmicutes bacilli lactobacillales streptococcaceae lactococcus lactococcus_lactis lactococcus genus bacteria firmicutes bacilli lactobacillales streptococcaceae lactococcus bacteroides_uniformis_unclassified strain bacteria bacteroidetes bacteroidia bacteroidales bacteroidaceae bacteroides bacteroides_uniformis bacteroides_uniformis_unclassified dorea_formicigenerans_unclassified strain bacteria firmicutes clostridia clostridiales lachnospiraceae dorea dorea_formicigenerans dorea_formicigenerans_unclassified dorea_formicigenerans species bacteria firmicutes clostridia clostridiales lachnospiraceae dorea dorea_formicigenerans bacteroides_vulgatus_unclassified strain bacteria bacteroidetes bacteroidia bacteroidales bacteroidaceae bacteroides bacteroides_vulgatus bacteroides_vulgatus_unclassified clostridiaceae family bacteria firmicutes clostridia clostridiales clostridiaceae clostridium genus bacteria firmicutes clostridia clostridiales clostridiaceae clostridium gcf_000188175 strain bacteria firmicutes negativicutes selenomonadales acidaminococcaceae phascolarctobacterium phascolarctobacterium_succinatutens gcf_000188175 phascolarctobacterium_succinatutens species bacteria firmicutes negativicutes selenomonadales acidaminococcaceae phascolarctobacterium phascolarctobacterium_succinatutens phascolarctobacterium genus bacteria firmicutes negativicutes selenomonadales acidaminococcaceae phascolarctobacterium anaerostipes genus bacteria firmicutes clostridia clostridiales lachnospiraceae anaerostipes parabacteroides_goldsteinii_unclassified strain bacteria bacteroidetes bacteroidia bacteroidales porphyromonadaceae parabacteroides parabacteroides_goldsteinii parabacteroides_goldsteinii_unclassified parabacteroides_goldsteinii species bacteria bacteroidetes bacteroidia bacteroidales porphyromonadaceae parabacteroides parabacteroides_goldsteinii gcf_000154245 strain bacteria firmicutes clostridia clostridiales clostridiaceae clostridium clostridium_sp_l2_50 gcf_000154245 clostridium_sp_l2_50 species bacteria firmicutes clostridia clostridiales clostridiaceae clostridium clostridium_sp_l2_50 oscillibacter_unclassified species bacteria firmicutes clostridia clostridiales oscillospiraceae oscillibacter oscillibacter_unclassified bacteroides genus bacteria bacteroidetes bacteroidia bacteroidales bacteroidaceae bacteroides bacteroidaceae family bacteria bacteroidetes bacteroidia bacteroidales bacteroidaceae bacteroides_vulgatus species bacteria bacteroidetes bacteroidia bacteroidales bacteroidaceae bacteroides bacteroides_vulgatus gcf_000146185 strain bacteria firmicutes clostridia clostridiales eubacteriaceae eubacterium eubacterium_eligens gcf_000146185 eubacterium_eligens species bacteria firmicutes clostridia clostridiales eubacteriaceae eubacterium eubacterium_eligens gcf_000265365 strain bacteria bacteroidetes bacteroidia bacteroidales rikenellaceae alistipes alistipes_finegoldii gcf_000265365 alistipes_finegoldii species bacteria bacteroidetes bacteroidia bacteroidales rikenellaceae alistipes alistipes_finegoldii oxalobacter_formigenes species bacteria proteobacteria betaproteobacteria burkholderiales oxalobacteraceae oxalobacter oxalobacter_formigenes oxalobacter genus bacteria proteobacteria betaproteobacteria burkholderiales oxalobacteraceae oxalobacter oxalobacteraceae family bacteria proteobacteria betaproteobacteria burkholderiales oxalobacteraceae veillonellaceae family bacteria firmicutes negativicutes selenomonadales veillonellaceae gcf_000218385 strain bacteria firmicutes clostridia clostridiales lachnospiraceae lachnospiraceae_noname lachnospiraceae_bacterium_1_4_56faa gcf_000218385 lachnospiraceae_bacterium_1_4_56faa species bacteria firmicutes clostridia clostridiales lachnospiraceae lachnospiraceae_noname lachnospiraceae_bacterium_1_4_56faa bacteroides_dorei_unclassified strain bacteria bacteroidetes bacteroidia bacteroidales bacteroidaceae bacteroides bacteroides_dorei bacteroides_dorei_unclassified gcf_000242155 strain bacteria firmicutes clostridia clostridiales lachnospiraceae lachnospiraceae_noname lachnospiraceae_bacterium_7_1_58faa gcf_000242155 lachnospiraceae_bacterium_7_1_58faa species bacteria firmicutes clostridia clostridiales lachnospiraceae lachnospiraceae_noname lachnospiraceae_bacterium_7_1_58faa bacteroides_dorei species bacteria bacteroidetes bacteroidia bacteroidales bacteroidaceae bacteroides bacteroides_dorei gcf_000239295 strain bacteria firmicutes clostridia clostridiales clostridiales_noname flavonifractor flavonifractor_plautii gcf_000239295 flavonifractor_plautii species bacteria firmicutes clostridia clostridiales clostridiales_noname flavonifractor flavonifractor_plautii 1

Annotation Taxonomic label Taxonomic type Kingdom Phylum Class Order Family Genus Species Strain flavonifractor genus bacteria firmicutes clostridia clostridiales clostridiales_noname flavonifractor clostridiales_noname family bacteria firmicutes clostridia clostridiales clostridiales_noname clostridium_bolteae species bacteria firmicutes clostridia clostridiales clostridiaceae clostridium clostridium_bolteae gcf_000144975 strain bacteria proteobacteria betaproteobacteria burkholderiales burkholderiales_noname burkholderiales_noname burkholderiales_bacterium_1_1_47 gcf_000144975 burkholderiales_bacterium_1_1_47 species bacteria proteobacteria betaproteobacteria burkholderiales burkholderiales_noname burkholderiales_noname burkholderiales_bacterium_1_1_47 burkholderiales_noname genus bacteria proteobacteria betaproteobacteria burkholderiales burkholderiales_noname burkholderiales_noname dorea genus bacteria firmicutes clostridia clostridiales lachnospiraceae dorea burkholderiales_noname family bacteria proteobacteria betaproteobacteria burkholderiales burkholderiales_noname gcf_000024265 strain bacteria actinobacteria actinobacteria coriobacteriales coriobacteriaceae eggerthella eggerthella_lenta gcf_000024265 eggerthella_lenta species bacteria actinobacteria actinobacteria coriobacteriales coriobacteriaceae eggerthella eggerthella_lenta oscillibacter genus bacteria firmicutes clostridia clostridiales oscillospiraceae oscillibacter oscillospiraceae family bacteria firmicutes clostridia clostridiales oscillospiraceae subdoligranulum genus bacteria firmicutes clostridia clostridiales ruminococcaceae subdoligranulum gcf_000154445 strain bacteria firmicutes clostridia clostridiales peptostreptococcaceae peptostreptococcaceae_noname clostridium_bartlettii gcf_000154445 clostridium_bartlettii species bacteria firmicutes clostridia clostridiales peptostreptococcaceae peptostreptococcaceae_noname clostridium_bartlettii gcf_000231275 strain bacteria bacteroidetes bacteroidia bacteroidales rikenellaceae alistipes alistipes_indistinctus gcf_000231275 alistipes_indistinctus species bacteria bacteroidetes bacteroidia bacteroidales rikenellaceae alistipes alistipes_indistinctus subdoligranulum_unclassified species bacteria firmicutes clostridia clostridiales ruminococcaceae subdoligranulum subdoligranulum_unclassified bacteroides_cellulosilyticus species bacteria bacteroidetes bacteroidia bacteroidales bacteroidaceae bacteroides bacteroides_cellulosilyticus veillonella_unclassified species bacteria firmicutes negativicutes selenomonadales veillonellaceae veillonella veillonella_unclassified ruminococcus_torques_unclassified strain bacteria firmicutes clostridia clostridiales lachnospiraceae blautia ruminococcus_torques ruminococcus_torques_unclassified gcf_000374505 strain bacteria bacteroidetes bacteroidia bacteroidales rikenellaceae alistipes alistipes_onderdonkii gcf_000374505 alistipes_onderdonkii species bacteria bacteroidetes bacteroidia bacteroidales rikenellaceae alistipes alistipes_onderdonkii bacteroides_cellulosilyticus_unclassified strain bacteria bacteroidetes bacteroidia bacteroidales bacteroidaceae bacteroides bacteroides_cellulosilyticus bacteroides_cellulosilyticus_unclassified gcf_000154365 strain bacteria firmicutes clostridia clostridiales clostridiaceae clostridium clostridium_bolteae gcf_000154365 bifidobacterium_longum species bacteria actinobacteria actinobacteria bifidobacteriales bifidobacteriaceae bifidobacterium bifidobacterium_longum gcf_000154065 strain bacteria firmicutes clostridia clostridiales lachnospiraceae dorea dorea_longicatena gcf_000154065 dorea_longicatena species bacteria firmicutes clostridia clostridiales lachnospiraceae dorea dorea_longicatena bifidobacterium_longum_unclassified strain bacteria actinobacteria actinobacteria bifidobacteriales bifidobacteriaceae bifidobacterium bifidobacterium_longum bifidobacterium_longum_unclassified gcf_000478885 strain bacteria actinobacteria actinobacteria coriobacteriales coriobacteriaceae adlercreutzia adlercreutzia_equolifaciens gcf_000478885 adlercreutzia_equolifaciens species bacteria actinobacteria actinobacteria coriobacteriales coriobacteriaceae adlercreutzia adlercreutzia_equolifaciens adlercreutzia genus bacteria actinobacteria actinobacteria coriobacteriales coriobacteriaceae adlercreutzia erysipelotrichaceae_noname genus bacteria firmicutes erysipelotrichia erysipelotrichales erysipelotrichaceae erysipelotrichaceae_noname dialister genus bacteria firmicutes negativicutes selenomonadales veillonellaceae dialister gcf_000195615 strain bacteria bacteroidetes bacteroidia bacteroidales bacteroidaceae bacteroides bacteroides_clarus gcf_000195615 bacteroides_clarus species bacteria bacteroidetes bacteroidia bacteroidales bacteroidaceae bacteroides bacteroides_clarus ruminococcus_lactaris species bacteria firmicutes clostridia clostridiales ruminococcaceae ruminococcus ruminococcus_lactaris ruminococcus_lactaris_unclassified strain bacteria firmicutes clostridia clostridiales ruminococcaceae ruminococcus ruminococcus_lactaris ruminococcus_lactaris_unclassified gcf_000209875 strain bacteria firmicutes clostridia clostridiales ruminococcaceae ruminococcus ruminococcus_bromii gcf_000209875 ruminococcus_bromii species bacteria firmicutes clostridia clostridiales ruminococcaceae ruminococcus ruminococcus_bromii klebsiella genus bacteria proteobacteria gammaproteobacteria enterobacteriales enterobacteriaceae klebsiella veillonella_atypica_unclassified strain bacteria firmicutes negativicutes selenomonadales veillonellaceae veillonella veillonella_atypica veillonella_atypica_unclassified veillonella_atypica species bacteria firmicutes negativicutes selenomonadales veillonellaceae veillonella veillonella_atypica acidaminococcaceae family bacteria firmicutes negativicutes selenomonadales acidaminococcaceae viruses_noname class viruses viruses_noname viruses_noname viruses_noname phylum viruses viruses_noname viruses kingdom viruses eubacterium_sp_3_1_31_unclassified strain bacteria firmicutes clostridia clostridiales eubacteriaceae eubacterium eubacterium_sp_3_1_31 eubacterium_sp_3_1_31_unclassified eubacterium_sp_3_1_31 species bacteria firmicutes clostridia clostridiales eubacteriaceae eubacterium eubacterium_sp_3_1_31 prevotellaceae family bacteria bacteroidetes bacteroidia bacteroidales prevotellaceae gcf_000242175 strain bacteria firmicutes erysipelotrichia erysipelotrichales erysipelotrichaceae erysipelotrichaceae_noname erysipelotrichaceae_bacterium_6_1_45 gcf_000242175 erysipelotrichaceae_bacterium_6_1_45 species bacteria firmicutes erysipelotrichia erysipelotrichales erysipelotrichaceae erysipelotrichaceae_noname erysipelotrichaceae_bacterium_6_1_45 gcf_000153885 strain bacteria firmicutes clostridia clostridiales eubacteriaceae eubacterium eubacterium_ventriosum gcf_000153885 eubacterium_ventriosum species bacteria firmicutes clostridia clostridiales eubacteriaceae eubacterium eubacterium_ventriosum streptococcus_vestibularis_unclassified strain bacteria firmicutes bacilli lactobacillales streptococcaceae streptococcus streptococcus_vestibularis streptococcus_vestibularis_unclassified streptococcus_vestibularis species bacteria firmicutes bacilli lactobacillales streptococcaceae streptococcus streptococcus_vestibularis gcf_000160055 strain bacteria firmicutes negativicutes selenomonadales veillonellaceae dialister dialister_invisus gcf_000160055 dialister_invisus species bacteria firmicutes negativicutes selenomonadales veillonellaceae dialister dialister_invisus gcf_000218465 strain bacteria firmicutes clostridia clostridiales lachnospiraceae lachnospiraceae_noname lachnospiraceae_bacterium_2_1_58faa gcf_000218465 lachnospiraceae_bacterium_2_1_58faa species bacteria firmicutes clostridia clostridiales lachnospiraceae lachnospiraceae_noname lachnospiraceae_bacterium_2_1_58faa gcf_000187895 strain bacteria bacteroidetes bacteroidia bacteroidales bacteroidaceae bacteroides bacteroides_plebeius gcf_000187895 bacteroides_plebeius species bacteria bacteroidetes bacteroidia bacteroidales bacteroidaceae bacteroides bacteroides_plebeius prevotella genus bacteria bacteroidetes bacteroidia bacteroidales prevotellaceae prevotella proteobacteria phylum bacteria proteobacteria gcf_000332875 strain bacteria firmicutes clostridia clostridiales lachnospiraceae anaerostipes anaerostipes_hadrus gcf_000332875 anaerostipes_hadrus species bacteria firmicutes clostridia clostridiales lachnospiraceae anaerostipes anaerostipes_hadrus lachnospiraceae family bacteria firmicutes clostridia clostridiales lachnospiraceae bifidobacterium_adolescentis_unclassified strain bacteria actinobacteria actinobacteria bifidobacteriales bifidobacteriaceae bifidobacterium bifidobacterium_adolescentis bifidobacterium_adolescentis_unclassified bifidobacterium_adolescentis species bacteria actinobacteria actinobacteria bifidobacteriales bifidobacteriaceae bifidobacterium bifidobacterium_adolescentis gcf_000312145 strain bacteria bacteroidetes bacteroidia bacteroidales rikenellaceae alistipes alistipes_senegalensis gcf_000312145 alistipes_senegalensis species bacteria bacteroidetes bacteroidia bacteroidales rikenellaceae alistipes alistipes_senegalensis roseburia genus bacteria firmicutes clostridia clostridiales lachnospiraceae roseburia alistipes genus bacteria bacteroidetes bacteroidia bacteroidales rikenellaceae alistipes rikenellaceae family bacteria bacteroidetes bacteroidia bacteroidales rikenellaceae bacteria kingdom bacteria 2

Annotation Taxonomic label Taxonomic type Kingdom Phylum Class Order Family Genus Species Strain gcf_000205165 strain bacteria bacteroidetes bacteroidia bacteroidales prevotellaceae paraprevotella paraprevotella_xylaniphila gcf_000205165 paraprevotella_xylaniphila species bacteria bacteroidetes bacteroidia bacteroidales prevotellaceae paraprevotella paraprevotella_xylaniphila gcf_000226135 strain bacteria bacteroidetes bacteroidia bacteroidales bacteroidaceae bacteroides bacteroides_faecis gcf_000226135 bacteroides_faecis species bacteria bacteroidetes bacteroidia bacteroidales bacteroidaceae bacteroides bacteroides_faecis gcf_000157935 strain bacteria bacteroidetes bacteroidia bacteroidales prevotellaceae prevotella prevotella_copri gcf_000157935 prevotella_copri species bacteria bacteroidetes bacteroidia bacteroidales prevotellaceae prevotella prevotella_copri gcf_000173435 strain bacteria actinobacteria actinobacteria bifidobacteriales bifidobacteriaceae bifidobacterium bifidobacterium_pseudocatenulatum gcf_000173435 bifidobacterium_pseudocatenulatum species bacteria actinobacteria actinobacteria bifidobacteriales bifidobacteriaceae bifidobacterium bifidobacterium_pseudocatenulatum gcf_000468015 strain bacteria firmicutes clostridia clostridiales ruminococcaceae ruminococcus ruminococcus_callidus gcf_000468015 ruminococcus_callidus species bacteria firmicutes clostridia clostridiales ruminococcaceae ruminococcus ruminococcus_callidus gcf_000218445 strain bacteria firmicutes clostridia clostridiales lachnospiraceae lachnospiraceae_noname lachnospiraceae_bacterium_1_1_57faa gcf_000218445 lachnospiraceae_bacterium_1_1_57faa species bacteria firmicutes clostridia clostridiales lachnospiraceae lachnospiraceae_noname lachnospiraceae_bacterium_1_1_57faa gcf_000169255 strain bacteria firmicutes clostridia clostridiales clostridiales_noname pseudoflavonifractor pseudoflavonifractor_capillosus gcf_000169255 pseudoflavonifractor_capillosus species bacteria firmicutes clostridia clostridiales clostridiales_noname pseudoflavonifractor pseudoflavonifractor_capillosus pseudoflavonifractor genus bacteria firmicutes clostridia clostridiales clostridiales_noname pseudoflavonifractor lactobacillus genus bacteria firmicutes bacilli lactobacillales lactobacillaceae lactobacillus ruminococcus_torques species bacteria firmicutes clostridia clostridiales lachnospiraceae blautia ruminococcus_torques gcf_000154205 strain bacteria bacteroidetes bacteroidia bacteroidales bacteroidaceae bacteroides bacteroides_uniformis gcf_000154205 eubacterium genus bacteria firmicutes clostridia clostridiales eubacteriaceae eubacterium eubacteriaceae family bacteria firmicutes clostridia clostridiales eubacteriaceae holdemania genus bacteria firmicutes erysipelotrichia erysipelotrichales erysipelotrichaceae holdemania desulfovibrio genus bacteria proteobacteria deltaproteobacteria desulfovibrionales desulfovibrionaceae desulfovibrio odoribacter_unclassified species bacteria bacteroidetes bacteroidia bacteroidales porphyromonadaceae odoribacter odoribacter_unclassified gcf_000185705 strain bacteria proteobacteria deltaproteobacteria desulfovibrionales desulfovibrionaceae bilophila bilophila_wadsworthia gcf_000185705 bilophila_wadsworthia species bacteria proteobacteria deltaproteobacteria desulfovibrionales desulfovibrionaceae bilophila bilophila_wadsworthia erysipelotrichaceae family bacteria firmicutes erysipelotrichia erysipelotrichales erysipelotrichaceae erysipelotrichales order bacteria firmicutes erysipelotrichia erysipelotrichales erysipelotrichia class bacteria firmicutes erysipelotrichia sutterella_wadsworthensis species bacteria proteobacteria betaproteobacteria burkholderiales sutterellaceae sutterella sutterella_wadsworthensis bifidobacterium_bifidum_unclassified strain bacteria actinobacteria actinobacteria bifidobacteriales bifidobacteriaceae bifidobacterium bifidobacterium_bifidum bifidobacterium_bifidum_unclassified bifidobacterium_bifidum species bacteria actinobacteria actinobacteria bifidobacteriales bifidobacteriaceae bifidobacterium bifidobacterium_bifidum desulfovibrio_desulfuricans species bacteria proteobacteria deltaproteobacteria desulfovibrionales desulfovibrionaceae desulfovibrio desulfovibrio_desulfuricans gcf_000154465 strain bacteria bacteroidetes bacteroidia bacteroidales rikenellaceae alistipes alistipes_putredinis gcf_000154465 alistipes_putredinis species bacteria bacteroidetes bacteroidia bacteroidales rikenellaceae alistipes alistipes_putredinis lactobacillales order bacteria firmicutes bacilli lactobacillales eubacterium_rectale_unclassified strain bacteria firmicutes clostridia clostridiales eubacteriaceae eubacterium eubacterium_rectale eubacterium_rectale_unclassified eubacterium_rectale species bacteria firmicutes clostridia clostridiales eubacteriaceae eubacterium eubacterium_rectale selenomonadales order bacteria firmicutes negativicutes selenomonadales negativicutes class bacteria firmicutes negativicutes ruminococcaceae family bacteria firmicutes clostridia clostridiales ruminococcaceae bacilli class bacteria firmicutes bacilli parabacteroides_johnsonii species bacteria bacteroidetes bacteroidia bacteroidales porphyromonadaceae parabacteroides parabacteroides_johnsonii sutterella genus bacteria proteobacteria betaproteobacteria burkholderiales sutterellaceae sutterella methanobrevibacter genus archaea euryarchaeota methanobacteria methanobacteriales methanobacteriaceae methanobrevibacter peptostreptococcaceae_noname_unclassified species bacteria firmicutes clostridia clostridiales peptostreptococcaceae peptostreptococcaceae_noname peptostreptococcaceae_noname_unclassified parabacteroides_distasonis_unclassified strain bacteria bacteroidetes bacteroidia bacteroidales porphyromonadaceae parabacteroides parabacteroides_distasonis parabacteroides_distasonis_unclassified parabacteroides_distasonis species bacteria bacteroidetes bacteroidia bacteroidales porphyromonadaceae parabacteroides parabacteroides_distasonis siphoviridae family viruses viruses_noname viruses_noname caudovirales siphoviridae gcf_000311925 strain bacteria bacteroidetes bacteroidia bacteroidales bacteroidales_noname bacteroidales_noname bacteroidales_bacterium_ph8 gcf_000311925 bacteroidales_bacterium_ph8 species bacteria bacteroidetes bacteroidia bacteroidales bacteroidales_noname bacteroidales_noname bacteroidales_bacterium_ph8 bacteroidales_noname genus bacteria bacteroidetes bacteroidia bacteroidales bacteroidales_noname bacteroidales_noname bacteroidales_noname family bacteria bacteroidetes bacteroidia bacteroidales bacteroidales_noname euryarchaeota phylum archaea euryarchaeota archaea kingdom archaea methanobacteriaceae family archaea euryarchaeota methanobacteria methanobacteriales methanobacteriaceae methanobacteriales order archaea euryarchaeota methanobacteria methanobacteriales methanobacteria class archaea euryarchaeota methanobacteria methanobrevibacter_smithii_unclassified strain archaea euryarchaeota methanobacteria methanobacteriales methanobacteriaceae methanobrevibacter methanobrevibacter_smithii methanobrevibacter_smithii_unclassified methanobrevibacter_smithii species archaea euryarchaeota methanobacteria methanobacteriales methanobacteriaceae methanobrevibacter methanobrevibacter_smithii gcf_000155875 strain bacteria firmicutes clostridia clostridiales lachnospiraceae coprococcus coprococcus_comes gcf_000155875 coprococcus_comes species bacteria firmicutes clostridia clostridiales lachnospiraceae coprococcus coprococcus_comes propionibacteriaceae family bacteria actinobacteria actinobacteria actinomycetales propionibacteriaceae lactobacillaceae family bacteria firmicutes bacilli lactobacillales lactobacillaceae bacteroides_ovatus_unclassified strain bacteria bacteroidetes bacteroidia bacteroidales bacteroidaceae bacteroides bacteroides_ovatus bacteroides_ovatus_unclassified gcf_000157995 strain bacteria firmicutes erysipelotrichia erysipelotrichales erysipelotrichaceae holdemania holdemania_filiformis gcf_000157995 holdemania_filiformis species bacteria firmicutes erysipelotrichia erysipelotrichales erysipelotrichaceae holdemania holdemania_filiformis butyrivibrio genus bacteria firmicutes clostridia clostridiales lachnospiraceae butyrivibrio gcf_000210595 strain bacteria firmicutes clostridia clostridiales lachnospiraceae coprococcus coprococcus_sp_art55_1 gcf_000210595 coprococcus_sp_art55_1 species bacteria firmicutes clostridia clostridiales lachnospiraceae coprococcus coprococcus_sp_art55_1 gcf_000156015 strain bacteria firmicutes clostridia clostridiales lachnospiraceae butyrivibrio butyrivibrio_crossotus gcf_000156015 butyrivibrio_crossotus species bacteria firmicutes clostridia clostridiales lachnospiraceae butyrivibrio butyrivibrio_crossotus streptococcus_salivarius_unclassified strain bacteria firmicutes bacilli lactobacillales streptococcaceae streptococcus streptococcus_salivarius streptococcus_salivarius_unclassified streptococcus_salivarius species bacteria firmicutes bacilli lactobacillales streptococcaceae streptococcus streptococcus_salivarius bacteroides_finegoldii species bacteria bacteroidetes bacteroidia bacteroidales bacteroidaceae bacteroides bacteroides_finegoldii gcf_000173795 strain bacteria firmicutes erysipelotrichia erysipelotrichales erysipelotrichaceae catenibacterium catenibacterium_mitsuokai gcf_000173795 3

Annotation Taxonomic label Taxonomic type Kingdom Phylum Class Order Family Genus Species Strain catenibacterium_mitsuokai species bacteria firmicutes erysipelotrichia erysipelotrichales erysipelotrichaceae catenibacterium catenibacterium_mitsuokai catenibacterium genus bacteria firmicutes erysipelotrichia erysipelotrichales erysipelotrichaceae catenibacterium veillonella genus bacteria firmicutes negativicutes selenomonadales veillonellaceae veillonella gcf_000159975 strain bacteria firmicutes clostridia clostridiales ruminococcaceae ruminococcus ruminococcus_sp_5_1_39bfaa gcf_000159975 ruminococcus_sp_5_1_39bfaa species bacteria firmicutes clostridia clostridiales ruminococcaceae ruminococcus ruminococcus_sp_5_1_39bfaa veillonella_parvula_unclassified strain bacteria firmicutes negativicutes selenomonadales veillonellaceae veillonella veillonella_parvula veillonella_parvula_unclassified veillonella_parvula species bacteria firmicutes negativicutes selenomonadales veillonellaceae veillonella veillonella_parvula gcf_000020225 strain bacteria verrucomicrobia verrucomicrobiae verrucomicrobiales verrucomicrobiaceae akkermansia akkermansia_muciniphila gcf_000020225 akkermansia_muciniphila species bacteria verrucomicrobia verrucomicrobiae verrucomicrobiales verrucomicrobiaceae akkermansia akkermansia_muciniphila akkermansia genus bacteria verrucomicrobia verrucomicrobiae verrucomicrobiales verrucomicrobiaceae akkermansia verrucomicrobiaceae family bacteria verrucomicrobia verrucomicrobiae verrucomicrobiales verrucomicrobiaceae verrucomicrobiales order bacteria verrucomicrobia verrucomicrobiae verrucomicrobiales verrucomicrobiae class bacteria verrucomicrobia verrucomicrobiae verrucomicrobia phylum bacteria verrucomicrobia parabacteroides_merdae_unclassified strain bacteria bacteroidetes bacteroidia bacteroidales porphyromonadaceae parabacteroides parabacteroides_merdae parabacteroides_merdae_unclassified parabacteroides_merdae species bacteria bacteroidetes bacteroidia bacteroidales porphyromonadaceae parabacteroides parabacteroides_merdae gcf_000473955 strain bacteria bacteroidetes bacteroidia bacteroidales porphyromonadaceae coprobacter coprobacter_fastidiosus gcf_000473955 coprobacter_fastidiosus species bacteria bacteroidetes bacteroidia bacteroidales porphyromonadaceae coprobacter coprobacter_fastidiosus coprobacter genus bacteria bacteroidetes bacteroidia bacteroidales porphyromonadaceae coprobacter streptococcaceae family bacteria firmicutes bacilli lactobacillales streptococcaceae gcf_000174195 strain bacteria firmicutes clostridia clostridiales lachnospiraceae roseburia roseburia_inulinivorans gcf_000174195 roseburia_inulinivorans species bacteria firmicutes clostridia clostridiales lachnospiraceae roseburia roseburia_inulinivorans ruminococcus_obeum_unclassified strain bacteria firmicutes clostridia clostridiales lachnospiraceae blautia ruminococcus_obeum ruminococcus_obeum_unclassified bacteroides_xylanisolvens_unclassified strain bacteria bacteroidetes bacteroidia bacteroidales bacteroidaceae bacteroides bacteroides_xylanisolvens bacteroides_xylanisolvens_unclassified bacteroides_xylanisolvens species bacteria bacteroidetes bacteroidia bacteroidales bacteroidaceae bacteroides bacteroides_xylanisolvens gcf_000210555 strain bacteria firmicutes clostridia clostridiales lachnospiraceae coprococcus coprococcus_catus gcf_000210555 coprococcus_catus species bacteria firmicutes clostridia clostridiales lachnospiraceae coprococcus coprococcus_catus collinsella genus bacteria actinobacteria actinobacteria coriobacteriales coriobacteriaceae collinsella ruminococcus_gnavus_unclassified strain bacteria firmicutes clostridia clostridiales lachnospiraceae blautia ruminococcus_gnavus ruminococcus_gnavus_unclassified ruminococcus_gnavus species bacteria firmicutes clostridia clostridiales lachnospiraceae blautia ruminococcus_gnavus parabacteroides_johnsonii_unclassified strain bacteria bacteroidetes bacteroidia bacteroidales porphyromonadaceae parabacteroides parabacteroides_johnsonii parabacteroides_johnsonii_unclassified turicibacter genus bacteria firmicutes erysipelotrichia erysipelotrichales erysipelotrichaceae turicibacter gcf_000210055 strain bacteria actinobacteria actinobacteria coriobacteriales coriobacteriaceae gordonibacter gordonibacter_pamelaeae gcf_000210055 gordonibacter_pamelaeae species bacteria actinobacteria actinobacteria coriobacteriales coriobacteriaceae gordonibacter gordonibacter_pamelaeae gordonibacter genus bacteria actinobacteria actinobacteria coriobacteriales coriobacteriaceae gordonibacter paraprevotella genus bacteria bacteroidetes bacteroidia bacteroidales prevotellaceae paraprevotella paraprevotella_unclassified species bacteria bacteroidetes bacteroidia bacteroidales prevotellaceae paraprevotella paraprevotella_unclassified gcf_000209405 strain bacteria firmicutes clostridia clostridiales lachnospiraceae lachnospiraceae_noname lachnospiraceae_bacterium_3_1_46faa gcf_000209405 lachnospiraceae_bacterium_3_1_46faa species bacteria firmicutes clostridia clostridiales lachnospiraceae lachnospiraceae_noname lachnospiraceae_bacterium_3_1_46faa eubacterium_siraeum species bacteria firmicutes clostridia clostridiales eubacteriaceae eubacterium eubacterium_siraeum c2likevirus genus viruses viruses_noname viruses_noname caudovirales siphoviridae c2likevirus coriobacteriaceae family bacteria actinobacteria actinobacteria coriobacteriales coriobacteriaceae coriobacteriales order bacteria actinobacteria actinobacteria coriobacteriales gcf_000169035 strain bacteria actinobacteria actinobacteria coriobacteriales coriobacteriaceae collinsella collinsella_aerofaciens gcf_000169035 collinsella_aerofaciens species bacteria actinobacteria actinobacteria coriobacteriales coriobacteriaceae collinsella collinsella_aerofaciens anaerotruncus genus bacteria firmicutes clostridia clostridiales ruminococcaceae anaerotruncus gcf_000185545 strain bacteria firmicutes clostridia clostridiales lachnospiraceae lachnospiraceae_noname lachnospiraceae_bacterium_8_1_57faa gcf_000185545 lachnospiraceae_bacterium_8_1_57faa species bacteria firmicutes clostridia clostridiales lachnospiraceae lachnospiraceae_noname lachnospiraceae_bacterium_8_1_57faa caudovirales order viruses viruses_noname viruses_noname caudovirales acidaminococcus_unclassified species bacteria firmicutes negativicutes selenomonadales acidaminococcaceae acidaminococcus acidaminococcus_unclassified gcf_000273175 strain bacteria bacteroidetes bacteroidia bacteroidales bacteroidaceae bacteroides bacteroides_nordii gcf_000273175 bacteroides_nordii species bacteria bacteroidetes bacteroidia bacteroidales bacteroidaceae bacteroides bacteroides_nordii holdemania_unclassified species bacteria firmicutes erysipelotrichia erysipelotrichales erysipelotrichaceae holdemania holdemania_unclassified coprococcus genus bacteria firmicutes clostridia clostridiales lachnospiraceae coprococcus clostridiales order bacteria firmicutes clostridia clostridiales clostridia class bacteria firmicutes clostridia firmicutes phylum bacteria firmicutes gcf_000190535 strain bacteria bacteroidetes bacteroidia bacteroidales porphyromonadaceae odoribacter odoribacter_splanchnicus gcf_000190535 odoribacter_splanchnicus species bacteria bacteroidetes bacteroidia bacteroidales porphyromonadaceae odoribacter odoribacter_splanchnicus faecalibacterium_prausnitzii_unclassified strain bacteria firmicutes clostridia clostridiales ruminococcaceae faecalibacterium faecalibacterium_prausnitzii faecalibacterium_prausnitzii_unclassified streptococcus_parasanguinis_unclassified strain bacteria firmicutes bacilli lactobacillales streptococcaceae streptococcus streptococcus_parasanguinis streptococcus_parasanguinis_unclassified streptococcus_parasanguinis species bacteria firmicutes bacilli lactobacillales streptococcaceae streptococcus streptococcus_parasanguinis enterobacteriaceae family bacteria proteobacteria gammaproteobacteria enterobacteriales enterobacteriaceae enterobacteriales order bacteria proteobacteria gammaproteobacteria enterobacteriales eubacterium_siraeum_unclassified strain bacteria firmicutes clostridia clostridiales eubacteriaceae eubacterium eubacterium_siraeum eubacterium_siraeum_unclassified streptococcus genus bacteria firmicutes bacilli lactobacillales streptococcaceae streptococcus roseburia_unclassified species bacteria firmicutes clostridia clostridiales lachnospiraceae roseburia roseburia_unclassified bacteroides_fragilis species bacteria bacteroidetes bacteroidia bacteroidales bacteroidaceae bacteroides bacteroides_fragilis gcf_000469345 strain bacteria firmicutes clostridia clostridiales eubacteriaceae eubacterium eubacterium_ramulus gcf_000469345 eubacterium_ramulus species bacteria firmicutes clostridia clostridiales eubacteriaceae eubacterium eubacterium_ramulus escherichia_coli_unclassified strain bacteria proteobacteria gammaproteobacteria enterobacteriales enterobacteriaceae escherichia escherichia_coli escherichia_coli_unclassified escherichia_coli species bacteria proteobacteria gammaproteobacteria enterobacteriales enterobacteriaceae escherichia escherichia_coli escherichia genus bacteria proteobacteria gammaproteobacteria enterobacteriales enterobacteriaceae escherichia desulfovibrio_desulfuricans_unclassified strain bacteria proteobacteria deltaproteobacteria desulfovibrionales desulfovibrionaceae desulfovibrio desulfovibrio_desulfuricans desulfovibrio_desulfuricans_unclassified coprobacillus_unclassified species bacteria firmicutes erysipelotrichia erysipelotrichales erysipelotrichaceae coprobacillus coprobacillus_unclassified 4

Annotation Taxonomic label Taxonomic type Kingdom Phylum Class Order Family Genus Species Strain coprobacillus genus bacteria firmicutes erysipelotrichia erysipelotrichales erysipelotrichaceae coprobacillus c2likevirus_unclassified species viruses viruses_noname viruses_noname caudovirales siphoviridae c2likevirus c2likevirus_unclassified clostridium_bolteae_unclassified strain bacteria firmicutes clostridia clostridiales clostridiaceae clostridium clostridium_bolteae clostridium_bolteae_unclassified lachnospiraceae_noname genus bacteria firmicutes clostridia clostridiales lachnospiraceae lachnospiraceae_noname actinomycetales order bacteria actinobacteria actinobacteria actinomycetales peptostreptococcaceae family bacteria firmicutes clostridia clostridiales peptostreptococcaceae bacteroides_stercoris species bacteria bacteroidetes bacteroidia bacteroidales bacteroidaceae bacteroides bacteroides_stercoris gcf_000233955 strain bacteria bacteroidetes bacteroidia bacteroidales prevotellaceae paraprevotella paraprevotella_clara gcf_000233955 paraprevotella_clara species bacteria bacteroidetes bacteroidia bacteroidales prevotellaceae paraprevotella paraprevotella_clara streptococcus_thermophilus_unclassified strain bacteria firmicutes bacilli lactobacillales streptococcaceae streptococcus streptococcus_thermophilus streptococcus_thermophilus_unclassified streptococcus_thermophilus species bacteria firmicutes bacilli lactobacillales streptococcaceae streptococcus streptococcus_thermophilus desulfovibrionaceae family bacteria proteobacteria deltaproteobacteria desulfovibrionales desulfovibrionaceae desulfovibrionales order bacteria proteobacteria deltaproteobacteria desulfovibrionales deltaproteobacteria class bacteria proteobacteria deltaproteobacteria bifidobacteriaceae family bacteria actinobacteria actinobacteria bifidobacteriales bifidobacteriaceae bifidobacteriales order bacteria actinobacteria actinobacteria bifidobacteriales turicibacter_unclassified species bacteria firmicutes erysipelotrichia erysipelotrichales erysipelotrichaceae turicibacter turicibacter_unclassified bifidobacterium genus bacteria actinobacteria actinobacteria bifidobacteriales bifidobacteriaceae bifidobacterium methanobrevibacter_unclassified species archaea euryarchaeota methanobacteria methanobacteriales methanobacteriaceae methanobrevibacter methanobrevibacter_unclassified bacteroidetes phylum bacteria bacteroidetes bacteroidales order bacteria bacteroidetes bacteroidia bacteroidales bacteroidia class bacteria bacteroidetes bacteroidia bacteroides_eggerthii_unclassified strain bacteria bacteroidetes bacteroidia bacteroidales bacteroidaceae bacteroides bacteroides_eggerthii bacteroides_eggerthii_unclassified bacteroides_eggerthii species bacteria bacteroidetes bacteroidia bacteroidales bacteroidaceae bacteroides bacteroides_eggerthii bacteroides_caccae_unclassified strain bacteria bacteroidetes bacteroidia bacteroidales bacteroidaceae bacteroides bacteroides_caccae bacteroides_caccae_unclassified bacteroides_caccae species bacteria bacteroidetes bacteroidia bacteroidales bacteroidaceae bacteroides bacteroides_caccae haemophilus genus bacteria proteobacteria gammaproteobacteria pasteurellales pasteurellaceae haemophilus streptococcus_australis_unclassified strain bacteria firmicutes bacilli lactobacillales streptococcaceae streptococcus streptococcus_australis streptococcus_australis_unclassified streptococcus_australis species bacteria firmicutes bacilli lactobacillales streptococcaceae streptococcus streptococcus_australis odoribacter genus bacteria bacteroidetes bacteroidia bacteroidales porphyromonadaceae odoribacter ruminococcus_obeum species bacteria firmicutes clostridia clostridiales lachnospiraceae blautia ruminococcus_obeum bacteroides_stercoris_unclassified strain bacteria bacteroidetes bacteroidia bacteroidales bacteroidaceae bacteroides bacteroides_stercoris bacteroides_stercoris_unclassified alistipes_unclassified species bacteria bacteroidetes bacteroidia bacteroidales rikenellaceae alistipes alistipes_unclassified pasteurellaceae family bacteria proteobacteria gammaproteobacteria pasteurellales pasteurellaceae pasteurellales order bacteria proteobacteria gammaproteobacteria pasteurellales gcf_000154565 strain bacteria firmicutes clostridia clostridiales ruminococcaceae anaerotruncus anaerotruncus_colihominis gcf_000154565 anaerotruncus_colihominis species bacteria firmicutes clostridia clostridiales ruminococcaceae anaerotruncus anaerotruncus_colihominis haemophilus_parainfluenzae_unclassified strain bacteria proteobacteria gammaproteobacteria pasteurellales pasteurellaceae haemophilus haemophilus_parainfluenzae haemophilus_parainfluenzae_unclassified haemophilus_parainfluenzae species bacteria proteobacteria gammaproteobacteria pasteurellales pasteurellaceae haemophilus haemophilus_parainfluenzae gcf_000177015 strain bacteria firmicutes clostridia clostridiales ruminococcaceae ruminococcaceae_noname ruminococcaceae_bacterium_d16 gcf_000177015 ruminococcaceae_bacterium_d16 species bacteria firmicutes clostridia clostridiales ruminococcaceae ruminococcaceae_noname ruminococcaceae_bacterium_d16 ruminococcaceae_noname genus bacteria firmicutes clostridia clostridiales ruminococcaceae ruminococcaceae_noname gcf_000162015 strain bacteria firmicutes clostridia clostridiales ruminococcaceae faecalibacterium faecalibacterium_prausnitzii gcf_000162015 gammaproteobacteria class bacteria proteobacteria gammaproteobacteria bacteroides_finegoldii_unclassified strain bacteria bacteroidetes bacteroidia bacteroidales bacteroidaceae bacteroides bacteroides_finegoldii bacteroides_finegoldii_unclassified gcf_000154345 strain bacteria firmicutes clostridia clostridiales clostridiaceae clostridium clostridium_leptum gcf_000154345 clostridium_leptum species bacteria firmicutes clostridia clostridiales clostridiaceae clostridium clostridium_leptum sutterella_wadsworthensis_unclassified strain bacteria proteobacteria betaproteobacteria burkholderiales sutterellaceae sutterella sutterella_wadsworthensis sutterella_wadsworthensis_unclassified gcf_000154425 strain bacteria firmicutes clostridia clostridiales lachnospiraceae coprococcus coprococcus_eutactus gcf_000154425 coprococcus_eutactus species bacteria firmicutes clostridia clostridiales lachnospiraceae coprococcus coprococcus_eutactus bilophila_unclassified species bacteria proteobacteria deltaproteobacteria desulfovibrionales desulfovibrionaceae bilophila bilophila_unclassified gcf_000205025 strain bacteria proteobacteria betaproteobacteria burkholderiales sutterellaceae parasutterella parasutterella_excrementihominis gcf_000205025 parasutterella_excrementihominis species bacteria proteobacteria betaproteobacteria burkholderiales sutterellaceae parasutterella parasutterella_excrementihominis parasutterella genus bacteria proteobacteria betaproteobacteria burkholderiales sutterellaceae parasutterella bacteroides_fragilis_unclassified strain bacteria bacteroidetes bacteroidia bacteroidales bacteroidaceae bacteroides bacteroides_fragilis bacteroides_fragilis_unclassified dorea_unclassified species bacteria firmicutes clostridia clostridiales lachnospiraceae dorea dorea_unclassified blautia genus bacteria firmicutes clostridia clostridiales lachnospiraceae blautia gcf_000157975 strain bacteria firmicutes clostridia clostridiales lachnospiraceae blautia blautia_hydrogenotrophica gcf_000157975 blautia_hydrogenotrophica species bacteria firmicutes clostridia clostridiales lachnospiraceae blautia blautia_hydrogenotrophica actinobacteria class bacteria actinobacteria actinobacteria actinobacteria phylum bacteria actinobacteria gcf_000185525 strain bacteria firmicutes clostridia clostridiales lachnospiraceae lachnospiraceae_noname lachnospiraceae_bacterium_5_1_63faa gcf_000185525 lachnospiraceae_bacterium_5_1_63faa species bacteria firmicutes clostridia clostridiales lachnospiraceae lachnospiraceae_noname lachnospiraceae_bacterium_5_1_63faa bacteroides_thetaiotaomicron_unclassified strain bacteria bacteroidetes bacteroidia bacteroidales bacteroidaceae bacteroides bacteroides_thetaiotaomicron bacteroides_thetaiotaomicron_unclassified bilophila genus bacteria proteobacteria deltaproteobacteria desulfovibrionales desulfovibrionaceae bilophila bacteroides_thetaiotaomicron species bacteria bacteroidetes bacteroidia bacteroidales bacteroidaceae bacteroides bacteroides_thetaiotaomicron faecalibacterium_prausnitzii species bacteria firmicutes clostridia clostridiales ruminococcaceae faecalibacterium faecalibacterium_prausnitzii faecalibacterium genus bacteria firmicutes clostridia clostridiales ruminococcaceae faecalibacterium anaerotruncus_unclassified species bacteria firmicutes clostridia clostridiales ruminococcaceae anaerotruncus anaerotruncus_unclassified acidaminococcus genus bacteria firmicutes negativicutes selenomonadales acidaminococcaceae acidaminococcus roseburia_intestinalis_unclassified strain bacteria firmicutes clostridia clostridiales lachnospiraceae roseburia roseburia_intestinalis roseburia_intestinalis_unclassified roseburia_intestinalis species bacteria firmicutes clostridia clostridiales lachnospiraceae roseburia roseburia_intestinalis gcf_000296465 strain bacteria bacteroidetes bacteroidia bacteroidales porphyromonadaceae barnesiella barnesiella_intestinihominis gcf_000296465 barnesiella_intestinihominis species bacteria bacteroidetes bacteroidia bacteroidales porphyromonadaceae barnesiella barnesiella_intestinihominis barnesiella genus bacteria bacteroidetes bacteroidia bacteroidales porphyromonadaceae barnesiella 5

Annotation Taxonomic label Taxonomic type Kingdom Phylum Class Order Family Genus Species Strain parabacteroides genus bacteria bacteroidetes bacteroidia bacteroidales porphyromonadaceae parabacteroides escherichia_unclassified species bacteria proteobacteria gammaproteobacteria enterobacteriales enterobacteriaceae escherichia escherichia_unclassified ruminococcus genus bacteria firmicutes clostridia clostridiales ruminococcaceae ruminococcus oxalobacter_formigenes_unclassified strain bacteria proteobacteria betaproteobacteria burkholderiales oxalobacteraceae oxalobacter oxalobacter_formigenes oxalobacter_formigenes_unclassified bacteroides_salyersiae_unclassified strain bacteria bacteroidetes bacteroidia bacteroidales bacteroidaceae bacteroides bacteroides_salyersiae bacteroides_salyersiae_unclassified bacteroides_salyersiae species bacteria bacteroidetes bacteroidia bacteroidales bacteroidaceae bacteroides bacteroides_salyersiae peptostreptococcaceae_noname genus bacteria firmicutes clostridia clostridiales peptostreptococcaceae peptostreptococcaceae_noname parabacteroides_unclassified species bacteria bacteroidetes bacteroidia bacteroidales porphyromonadaceae parabacteroides parabacteroides_unclassified bacteroides_massiliensis_unclassified strain bacteria bacteroidetes bacteroidia bacteroidales bacteroidaceae bacteroides bacteroides_massiliensis bacteroides_massiliensis_unclassified bacteroides_massiliensis species bacteria bacteroidetes bacteroidia bacteroidales bacteroidaceae bacteroides bacteroides_massiliensis bacteroides_ovatus species bacteria bacteroidetes bacteroidia bacteroidales bacteroidaceae bacteroides bacteroides_ovatus porphyromonadaceae family bacteria bacteroidetes bacteroidia bacteroidales porphyromonadaceae

Supplementary Data 1a Supplementary Data 1a. Microbial associations with TMAO, and intakes of choline and red meat. Full model was adjusted for age, BMI, physical activity, energy intake, smoking, cumulative dietary quality (since 1986), antibiotics use, probiotics use, the Bristol Stool Chart, and/or fish intake (for non-fish dietary variables). Taxonomi Non- Average Plasma TMAO Choline Choline Red meat Red meat Taxonomic ID Taxonomic label c type missing n Abundance Effect P FDR Effect P Effect P Effect P Effect P s_39488 species eubacterium_hallii 860 6.9E-03 0.006 3.3E-04 1.3E-02 0.003 2.3E-01 0.001 6.1E-01 0.001 6.6E-01 -0.001 4.8E-01 t_GCF_000173975 strain gcf_000173975 860 6.9E-03 0.006 3.3E-04 1.3E-02 0.003 2.3E-01 0.001 6.1E-01 0.001 6.6E-01 -0.001 4.8E-01 s_1531 species clostridium_clostridioforme 136 1.4E-04 0.001 3.4E-04 1.3E-02 0.000 9.3E-01 0.000 4.1E-01 0.000 6.6E-01 0.000 4.4E-01 s_328814 species alistipes_shahii 726 1.0E-02 0.006 4.3E-04 1.3E-02 0.000 8.8E-01 0.000 9.1E-01 -0.001 6.9E-01 -0.002 3.6E-01 t_GCF_000210575 strain gcf_000210575 726 1.0E-02 0.006 4.3E-04 1.3E-02 0.000 8.8E-01 0.000 9.1E-01 -0.001 6.9E-01 -0.002 3.6E-01 s_457421 species clostridiales_bacterium_1_7_47faa 259 9.5E-05 0.001 4.6E-04 1.3E-02 0.000 6.5E-01 0.000 4.6E-01 0.000 2.8E-01 0.000 4.3E-01 t_GCF_000155435 strain gcf_000155435 259 9.5E-05 0.001 4.6E-04 1.3E-02 0.000 6.5E-01 0.000 4.6E-01 0.000 2.8E-01 0.000 4.3E-01 s_29361 species clostridium_nexile 133 8.9E-04 -0.003 5.0E-04 1.3E-02 0.000 9.0E-01 0.001 5.8E-01 0.002 2.2E-01 0.000 7.8E-01 t_GCF_000156035 strain gcf_000156035 133 8.9E-04 -0.003 5.0E-04 1.3E-02 0.000 9.0E-01 0.001 5.8E-01 0.002 2.2E-01 0.000 7.8E-01 s_301301 species roseburia_hominis 822 5.8E-03 0.006 5.5E-04 1.3E-02 -0.001 8.1E-01 -0.002 4.3E-01 0.000 9.5E-01 -0.001 5.2E-01 t_GCF_000225345 strain gcf_000225345 822 5.8E-03 0.006 5.5E-04 1.3E-02 -0.001 8.1E-01 -0.002 4.3E-01 0.000 9.5E-01 -0.001 5.2E-01 s_358743 species clostridium_citroniae 277 5.3E-05 0.001 1.1E-03 2.2E-02 0.000 6.8E-01 0.000 6.7E-01 0.000 1.6E-01 0.000 7.0E-01 t_GCF_000233455 strain gcf_000233455 277 5.3E-05 0.001 1.1E-03 2.3E-02 0.000 6.8E-01 0.000 6.7E-01 0.000 1.6E-01 0.000 7.0E-01 t_Clostridium_clostridiofor strain clostridium_clostridioforme_unclassified 134 1.1E-04 0.001 1.9E-03 3.3E-02 0.000 9.5E-01 0.000 4.4E-01 0.000 9.6E-01 0.000 3.0E-01 g_995019_unclass genus sutterellaceae_unclassified 267 9.6E-04 0.003 2.0E-03 1.2E-01 0.002 3.0E-01 0.000 7.7E-01 0.000 9.8E-01 0.002 1.9E-02 s_658657 species erysipelotrichaceae_bacterium_21_3 245 5.0E-05 0.001 2.1E-03 3.4E-02 0.000 2.3E-01 0.000 5.7E-01 0.000 3.4E-01 0.000 7.6E-02 t_GCF_000242195 strain gcf_000242195 245 5.0E-05 0.001 2.1E-03 3.3E-02 0.000 2.3E-01 0.000 5.7E-01 0.000 3.4E-01 0.000 7.6E-02 s_84111_unclass species eggerthella_unclassified 512 8.7E-04 0.002 2.2E-03 3.4E-02 0.000 9.8E-01 0.001 3.7E-01 0.000 7.0E-01 -0.001 1.1E-01 s_1735 species eubacterium_biforme 226 2.6E-03 -0.004 3.0E-03 4.1E-02 -0.001 5.7E-01 -0.001 5.3E-01 -0.003 1.8E-01 0.003 1.2E-02 t_GCF_000156655 strain gcf_000156655 226 2.6E-03 -0.004 3.0E-03 4.1E-02 -0.001 5.7E-01 -0.001 5.3E-01 -0.003 1.8E-01 0.003 1.2E-02 o_80840 order burkholderiales 776 5.1E-03 0.004 3.5E-03 5.3E-02 -0.001 6.3E-01 0.002 2.5E-01 0.000 9.8E-01 0.002 6.8E-02 t_GCF_000166035 strain gcf_000166035 148 3.1E-03 0.006 3.9E-03 4.8E-02 -0.001 7.0E-01 0.004 1.0E-01 -0.002 5.2E-01 0.001 7.0E-01 c_28216 class betaproteobacteria 776 5.1E-03 0.004 4.4E-03 5.3E-02 -0.001 6.4E-01 0.002 2.0E-01 0.000 9.8E-01 0.003 6.2E-02 f_995019 family sutterellaceae 726 4.3E-03 0.003 5.4E-03 1.6E-01 -0.001 5.8E-01 0.001 3.5E-01 -0.001 7.1E-01 0.002 6.0E-02 s_820 species bacteroides_uniformis 890 6.0E-02 -0.011 6.6E-03 8.3E-02 -0.002 8.1E-01 0.004 3.7E-01 0.003 6.1E-01 0.004 3.4E-01 s_154046 species clostridium_hathewayi 349 2.3E-04 0.001 7.6E-03 8.8E-02 0.000 7.1E-01 0.000 4.3E-01 0.000 6.9E-01 0.000 7.6E-01 s_333367 species clostridium_asparagiforme 411 2.3E-04 0.001 8.5E-03 9.0E-02 -0.001 3.4E-01 0.000 6.8E-01 0.001 3.2E-01 0.000 4.2E-01 t_GCF_000158075 strain gcf_000158075 411 2.3E-04 0.001 8.5E-03 9.5E-02 -0.001 3.4E-01 0.000 6.8E-01 0.001 3.2E-01 0.000 4.2E-01 g_84111 genus eggerthella 521 1.0E-03 0.002 9.8E-03 2.8E-01 0.000 8.8E-01 0.001 2.1E-01 -0.001 5.6E-01 -0.001 9.6E-02 s_658086 species lachnospiraceae_bacterium_3_1_57faa_ct1 334 3.6E-04 0.002 1.2E-02 1.2E-01 -0.001 2.5E-01 0.000 8.9E-01 0.000 8.4E-01 0.000 7.1E-01 t_GCF_000218405 strain gcf_000218405 334 3.6E-04 0.002 1.2E-02 1.2E-01 -0.001 2.5E-01 0.000 8.9E-01 0.000 8.4E-01 0.000 7.1E-01 t_Clostridium_hathewayi_unc strain clostridium_hathewayi_unclassified 346 2.1E-04 0.001 2.2E-02 2.0E-01 -0.001 4.6E-01 0.000 4.4E-01 0.000 8.7E-01 0.000 3.3E-01 s_329854 species bacteroides_intestinalis 268 4.9E-03 -0.004 2.3E-02 2.1E-01 0.010 1.2E-03 0.000 9.4E-01 -0.001 7.9E-01 0.001 5.4E-01 t_GCF_000172175 strain gcf_000172175 268 4.9E-03 -0.004 2.3E-02 2.0E-01 0.010 1.2E-03 0.000 9.4E-01 -0.001 7.9E-01 0.001 5.4E-01 s_1358 species lactococcus_lactis 203 2.8E-04 0.001 2.6E-02 2.2E-01 0.001 2.2E-01 0.001 1.2E-01 0.001 3.1E-01 0.001 8.9E-02 t_Lactococcus_lactis_unclas strain lactococcus_lactis_unclassified 203 2.8E-04 0.001 2.6E-02 2.1E-01 0.001 2.2E-01 0.001 1.2E-01 0.001 3.1E-01 0.001 8.9E-02 t_Bacteroides_uniformis_unc strain bacteroides_uniformis_unclassified 869 5.5E-02 -0.009 2.7E-02 2.1E-01 0.000 9.5E-01 0.005 2.9E-01 0.009 1.8E-01 0.005 2.0E-01 g_1357 genus lactococcus 205 2.8E-04 0.001 2.8E-02 3.1E-01 0.001 2.4E-01 0.001 1.4E-01 0.001 3.2E-01 0.001 9.2E-02 s_1512 species clostridium_symbiosum 320 3.6E-04 0.001 3.2E-02 2.6E-01 0.000 7.4E-01 0.001 2.4E-01 0.001 6.8E-02 0.000 9.7E-01 t_Clostridium_symbiosum_unc strain clostridium_symbiosum_unclassified 320 3.6E-04 0.001 3.2E-02 2.2E-01 0.000 7.4E-01 0.001 2.4E-01 0.001 6.8E-02 0.000 9.7E-01 t_Bacteroides_vulgatus_uncl strain bacteroides_vulgatus_unclassified 794 2.5E-02 -0.006 3.3E-02 2.2E-01 -0.010 5.0E-02 0.004 1.6E-01 0.004 3.4E-01 0.002 5.0E-01 g_186802_noname genus clostridiales_noname 331 2.5E-03 -0.003 3.5E-02 3.1E-01 0.000 9.2E-01 -0.001 5.5E-01 0.001 5.9E-01 0.000 7.5E-01 g_33024 genus phascolarctobacterium 105 3.5E-03 0.002 3.7E-02 3.1E-01 0.000 9.1E-01 -0.003 5.3E-02 -0.004 4.3E-02 0.001 6.2E-01 s_626940 species phascolarctobacterium_succinatutens 105 3.5E-03 0.002 3.7E-02 2.8E-01 0.000 9.1E-01 -0.003 5.3E-02 -0.004 4.3E-02 0.001 6.2E-01 t_GCF_000188175 strain gcf_000188175 105 3.5E-03 0.002 3.7E-02 2.4E-01 0.000 9.1E-01 -0.003 5.3E-02 -0.004 4.3E-02 0.001 6.2E-01 g_207244 genus anaerostipes 680 1.2E-03 0.002 3.7E-02 3.1E-01 0.004 2.0E-02 0.001 4.3E-01 0.001 6.5E-01 0.000 8.1E-01 f_31979 family clostridiaceae 845 1.3E-02 0.006 3.9E-02 3.3E-01 0.013 9.4E-03 -0.006 5.9E-02 -0.001 8.9E-01 -0.001 6.2E-01 g_1485 genus clostridium 845 1.3E-02 0.006 3.9E-02 3.1E-01 0.013 9.0E-03 -0.006 7.0E-02 -0.001 8.7E-01 -0.001 6.5E-01 s_214856 species alistipes_finegoldii 581 2.2E-03 0.002 4.2E-02 2.8E-01 -0.003 9.6E-02 -0.002 4.6E-02 -0.002 1.8E-01 0.001 4.7E-01 t_GCF_000265365 strain gcf_000265365 581 2.2E-03 0.002 4.2E-02 2.5E-01 -0.003 9.6E-02 -0.002 4.6E-02 -0.002 1.8E-01 0.001 4.7E-01 7

Supplementary Data 1a Taxonomi Non- Average Plasma TMAO Choline Choline Red meat Red meat Taxonomic ID Taxonomic label c type missing n Abundance Effect P FDR Effect P Effect P Effect P Effect P s_411489 species clostridium_sp_l2_50 93 5.9E-03 0.005 4.3E-02 2.8E-01 0.007 9.2E-02 -0.005 8.1E-02 -0.003 5.1E-01 -0.003 1.7E-01 t_GCF_000154245 strain gcf_000154245 93 5.9E-03 0.005 4.3E-02 2.5E-01 0.007 9.2E-02 -0.005 8.1E-02 -0.003 5.1E-01 -0.003 1.7E-01 f_815 family bacteroidaceae 925 2.4E-01 -0.011 4.3E-02 3.3E-01 -0.017 9.5E-02 -0.005 4.9E-01 0.006 4.8E-01 0.012 3.5E-02 g_816 genus bacteroides 925 2.4E-01 -0.011 4.3E-02 3.1E-01 -0.017 9.5E-02 -0.005 4.9E-01 0.006 4.8E-01 0.012 3.5E-02 f_31977 family veillonellaceae 655 1.4E-02 -0.006 4.5E-02 3.3E-01 -0.010 7.5E-02 0.005 1.5E-01 -0.011 2.3E-02 -0.005 1.1E-01 s_328812 species parabacteroides_goldsteinii 295 9.2E-04 0.001 4.6E-02 2.8E-01 0.000 7.7E-01 -0.001 4.8E-01 0.000 8.9E-01 0.000 5.7E-01 t_Parabacteroides_goldstein strain parabacteroides_goldsteinii_unclassified 295 9.2E-04 0.001 4.6E-02 2.5E-01 0.000 7.7E-01 -0.001 4.8E-01 0.000 8.9E-01 0.000 5.7E-01 s_39486 species dorea_formicigenerans 840 3.7E-03 0.002 4.7E-02 2.8E-01 0.002 2.9E-01 0.001 3.9E-01 0.003 9.2E-02 0.000 7.7E-01 t_Dorea_formicigenerans_unc strain dorea_formicigenerans_unclassified 840 3.7E-03 0.002 4.7E-02 2.5E-01 0.002 2.9E-01 0.001 3.9E-01 0.003 9.2E-02 0.000 7.7E-01 s_658655 species lachnospiraceae_bacterium_1_4_56faa 342 3.6E-04 0.001 4.8E-02 2.8E-01 -0.001 4.1E-01 -0.001 5.2E-02 0.000 9.0E-01 -0.001 3.0E-01 t_GCF_000218385 strain gcf_000218385 342 3.6E-04 0.001 4.8E-02 2.5E-01 -0.001 4.1E-01 -0.001 5.2E-02 0.000 9.0E-01 -0.001 3.0E-01 s_821 species bacteroides_vulgatus 797 2.5E-02 -0.005 4.9E-02 2.8E-01 -0.010 4.0E-02 0.004 2.7E-01 0.004 3.7E-01 0.003 3.0E-01 s_1681 species bifidobacterium_bifidum 119 1.6E-03 -0.002 5.0E-02 2.8E-01 0.006 6.7E-03 -0.002 1.3E-01 0.003 1.1E-01 0.000 8.6E-01 t_Bifidobacterium_bifidum_u strain bifidobacterium_bifidum_unclassified 119 1.6E-03 -0.002 5.0E-02 2.5E-01 0.006 6.7E-03 -0.002 1.3E-01 0.003 1.1E-01 0.000 8.6E-01 g_846 genus oxalobacter 176 1.3E-04 0.001 5.4E-02 3.5E-01 0.000 7.0E-01 0.001 1.3E-01 0.000 5.8E-01 0.000 8.8E-01 s_847 species oxalobacter_formigenes 176 1.3E-04 0.001 5.4E-02 2.9E-01 0.000 7.0E-01 0.001 1.3E-01 0.000 5.8E-01 0.000 8.8E-01 f_75682 family oxalobacteraceae 177 1.3E-04 0.001 5.6E-02 3.3E-01 0.000 7.0E-01 0.001 1.4E-01 0.000 5.6E-01 0.000 8.7E-01 t_Bacteroides_dorei_unclass strain bacteroides_dorei_unclassified 651 1.8E-02 -0.005 6.2E-02 2.9E-01 0.009 5.9E-02 -0.003 3.5E-01 0.001 9.0E-01 -0.004 1.5E-01 s_459786_unclass species oscillibacter_unclassified 876 4.8E-03 0.002 6.5E-02 3.3E-01 -0.002 3.9E-01 -0.002 2.5E-01 0.000 9.6E-01 0.000 9.6E-01 s_357276 species bacteroides_dorei 651 1.8E-02 -0.005 6.9E-02 3.3E-01 0.009 5.8E-02 -0.003 3.5E-01 0.001 8.6E-01 -0.004 1.5E-01 s_39485 species eubacterium_eligens 822 2.2E-02 -0.005 7.0E-02 3.3E-01 -0.001 8.8E-01 0.003 4.6E-01 -0.008 7.4E-02 -0.003 2.6E-01 t_GCF_000146185 strain gcf_000146185 822 2.2E-02 -0.005 7.0E-02 3.2E-01 -0.001 8.8E-01 0.003 4.6E-01 -0.008 7.4E-02 -0.003 2.6E-01 s_29465_unclass species veillonella_unclassified 538 1.2E-03 -0.002 7.4E-02 3.4E-01 0.000 9.7E-01 0.000 8.7E-01 0.002 2.0E-01 0.000 7.8E-01 f_186802_noname family clostridiales_noname 638 2.9E-03 -0.002 7.6E-02 3.7E-01 -0.001 6.3E-01 -0.001 7.4E-01 0.000 8.4E-01 -0.001 5.8E-01 s_208479 species clostridium_bolteae 459 2.0E-03 0.002 8.1E-02 3.6E-01 0.006 7.5E-03 -0.001 5.5E-01 0.000 8.1E-01 0.002 1.8E-01 s_84112 species eggerthella_lenta 219 1.0E-04 0.001 8.4E-02 3.6E-01 0.000 7.1E-01 0.000 1.6E-01 -0.001 1.1E-01 0.000 1.4E-01 t_GCF_000024265 strain gcf_000024265 219 1.0E-04 0.001 8.4E-02 3.7E-01 0.000 7.1E-01 0.000 1.6E-01 -0.001 1.1E-01 0.000 1.4E-01 g_80840_noname genus burkholderiales_noname 410 6.8E-04 -0.001 1.0E-01 5.1E-01 -0.001 2.5E-01 0.000 6.9E-01 -0.001 3.1E-01 0.000 5.8E-01 s_469610 species burkholderiales_bacterium_1_1_47 410 6.8E-04 -0.001 1.0E-01 4.2E-01 -0.001 2.5E-01 0.000 6.9E-01 -0.001 3.1E-01 0.000 5.8E-01 t_GCF_000144975 strain gcf_000144975 410 6.8E-04 -0.001 1.0E-01 4.2E-01 -0.001 2.5E-01 0.000 6.9E-01 -0.001 3.1E-01 0.000 5.8E-01 s_658087 species lachnospiraceae_bacterium_7_1_58faa 856 1.0E-03 0.001 1.0E-01 4.3E-01 0.000 6.0E-01 0.000 8.1E-01 0.001 1.0E-01 0.000 9.5E-01 t_GCF_000242155 strain gcf_000242155 856 1.0E-03 0.001 1.0E-01 4.2E-01 0.000 6.0E-01 0.000 8.1E-01 0.001 1.0E-01 0.000 9.5E-01 s_626932 species alistipes_indistinctus 446 1.2E-03 0.001 1.1E-01 4.3E-01 0.005 3.5E-03 0.001 3.3E-01 -0.001 5.9E-01 -0.001 5.0E-01 t_GCF_000231275 strain gcf_000231275 446 1.2E-03 0.001 1.1E-01 4.2E-01 0.005 3.5E-03 0.001 3.3E-01 -0.001 5.9E-01 -0.001 5.0E-01 t_Ruminococcus_torques_uncl strain ruminococcus_torques_unclassified 892 1.5E-02 0.003 1.1E-01 4.2E-01 -0.001 8.9E-01 -0.002 4.3E-01 0.002 4.4E-01 0.000 8.6E-01 g_946234 genus flavonifractor 391 3.2E-04 0.001 1.1E-01 5.1E-01 -0.001 1.4E-01 0.000 4.9E-01 -0.001 4.3E-01 0.000 6.0E-01 s_292800 species flavonifractor_plautii 391 3.2E-04 0.001 1.1E-01 4.4E-01 -0.001 1.4E-01 0.000 4.9E-01 -0.001 4.3E-01 0.000 6.0E-01 t_GCF_000239295 strain gcf_000239295 391 3.2E-04 0.001 1.1E-01 4.2E-01 -0.001 1.4E-01 0.000 4.9E-01 -0.001 4.3E-01 0.000 6.0E-01 s_246787 species bacteroides_cellulosilyticus 595 1.9E-02 0.004 1.3E-01 4.7E-01 -0.001 7.4E-01 0.003 2.6E-01 -0.003 5.0E-01 -0.001 7.1E-01 g_292632 genus subdoligranulum 924 6.7E-02 0.005 1.3E-01 5.1E-01 0.007 2.2E-01 -0.002 6.0E-01 0.012 1.8E-02 -0.001 7.0E-01 f_80840_noname family burkholderiales_noname 410 6.8E-04 -0.001 1.3E-01 5.4E-01 -0.001 2.4E-01 0.000 7.0E-01 -0.001 4.4E-01 0.000 7.2E-01 g_189330 genus dorea 902 1.2E-02 0.003 1.3E-01 5.1E-01 0.003 2.9E-01 0.004 7.7E-02 0.004 1.2E-01 0.000 8.4E-01 s_292632_unclass species subdoligranulum_unclassified 924 6.7E-02 0.004 1.4E-01 4.9E-01 0.007 2.3E-01 -0.002 5.9E-01 0.012 1.4E-02 -0.001 6.7E-01 t_Bacteroides_cellulosilyti strain bacteroides_cellulosilyticus_unclassified 595 1.8E-02 0.004 1.4E-01 4.7E-01 -0.002 7.3E-01 0.003 2.6E-01 -0.003 5.3E-01 -0.001 7.4E-01 s_46228 species ruminococcus_lactaris 506 5.8E-03 0.003 1.4E-01 4.9E-01 -0.006 9.9E-02 0.002 3.0E-01 0.004 1.7E-01 -0.001 4.5E-01 s_88431 species dorea_longicatena 763 7.5E-03 0.002 1.4E-01 4.9E-01 0.002 5.0E-01 0.002 3.4E-01 0.004 1.2E-01 0.000 8.5E-01 t_GCF_000154065 strain gcf_000154065 763 7.5E-03 0.002 1.4E-01 4.7E-01 0.002 5.0E-01 0.002 3.4E-01 0.004 1.2E-01 0.000 8.5E-01 t_Ruminococcus_lactaris_unc strain ruminococcus_lactaris_unclassified 506 5.8E-03 0.003 1.4E-01 4.7E-01 -0.005 1.0E-01 0.002 3.1E-01 0.004 1.5E-01 -0.001 4.6E-01 t_GCF_000154365 strain gcf_000154365 99 1.7E-03 0.002 1.4E-01 4.7E-01 0.008 4.9E-04 -0.001 3.9E-01 0.001 7.6E-01 0.002 2.4E-01 g_128827_noname genus erysipelotrichaceae_noname 676 3.3E-03 -0.002 1.4E-01 5.1E-01 -0.001 8.0E-01 -0.001 6.0E-01 0.000 8.3E-01 0.002 9.6E-02 s_216816 species bifidobacterium_longum 519 7.8E-03 -0.003 1.5E-01 4.9E-01 0.009 4.5E-02 -0.005 6.5E-02 0.000 9.3E-01 -0.003 2.3E-01 s_261299 species clostridium_bartlettii 230 1.8E-04 0.001 1.5E-01 4.9E-01 0.000 9.2E-01 0.001 3.3E-01 0.000 5.9E-01 0.000 9.7E-01 t_GCF_000154445 strain gcf_000154445 230 1.8E-04 0.001 1.5E-01 4.7E-01 0.000 9.2E-01 0.001 3.3E-01 0.000 5.9E-01 0.000 9.7E-01 8

Supplementary Data 1a Taxonomi Non- Average Plasma TMAO Choline Choline Red meat Red meat Taxonomic ID Taxonomic label c type missing n Abundance Effect P FDR Effect P Effect P Effect P Effect P t_Bifidobacterium_longum_un strain bifidobacterium_longum_unclassified 519 7.6E-03 -0.003 1.5E-01 4.7E-01 0.009 4.1E-02 -0.005 7.2E-02 0.000 9.4E-01 -0.003 2.4E-01 g_1578 genus lactobacillus 168 1.2E-03 -0.001 1.5E-01 5.1E-01 -0.001 4.7E-01 0.000 8.3E-01 -0.004 1.5E-02 0.000 7.5E-01 g_447020 genus adlercreutzia 777 1.9E-03 0.001 1.5E-01 5.1E-01 0.002 2.1E-01 0.001 5.2E-01 0.002 1.7E-01 -0.001 3.2E-01 s_446660 species adlercreutzia_equolifaciens 777 1.9E-03 0.001 1.5E-01 4.9E-01 0.002 2.1E-01 0.001 5.2E-01 0.002 1.7E-01 -0.001 3.2E-01 t_GCF_000478885 strain gcf_000478885 777 1.9E-03 0.001 1.5E-01 4.7E-01 0.002 2.1E-01 0.001 5.2E-01 0.002 1.7E-01 -0.001 3.2E-01 s_626929 species bacteroides_clarus 131 7.3E-04 0.001 1.6E-01 4.9E-01 -0.001 2.3E-01 0.000 5.4E-01 0.002 7.2E-02 0.002 1.1E-02 t_GCF_000195615 strain gcf_000195615 131 7.3E-04 0.001 1.6E-01 4.7E-01 -0.001 2.3E-01 0.000 5.4E-01 0.002 7.2E-02 0.002 1.1E-02 f_216572 family oscillospiraceae 904 5.4E-03 0.002 1.6E-01 5.4E-01 -0.003 1.8E-01 -0.002 2.1E-01 0.000 9.2E-01 0.000 9.8E-01 g_459786 genus oscillibacter 904 5.4E-03 0.002 1.6E-01 5.1E-01 -0.003 1.8E-01 -0.002 2.1E-01 0.000 9.2E-01 0.000 9.8E-01 g_39948 genus dialister 279 1.1E-02 -0.004 1.6E-01 5.1E-01 -0.011 3.0E-02 0.005 1.3E-01 -0.010 1.6E-02 -0.003 1.8E-01 s_328813 species alistipes_onderdonkii 762 1.5E-02 -0.004 1.6E-01 5.1E-01 -0.004 3.6E-01 -0.005 8.4E-02 -0.006 1.8E-01 -0.001 7.5E-01 t_GCF_000374505 strain gcf_000374505 762 1.5E-02 -0.004 1.6E-01 4.8E-01 -0.004 3.6E-01 -0.005 8.4E-02 -0.006 1.8E-01 -0.001 7.5E-01 g_570 genus klebsiella 100 2.2E-03 0.002 1.7E-01 5.1E-01 0.002 3.8E-01 -0.001 5.6E-01 -0.002 3.7E-01 0.000 7.7E-01 f_909930 family acidaminococcaceae 227 5.7E-03 0.002 1.7E-01 5.4E-01 -0.004 1.6E-01 -0.005 7.3E-03 -0.005 4.4E-02 0.001 6.1E-01 s_457402 species eubacterium_sp_3_1_31 201 3.2E-04 -0.001 1.9E-01 5.5E-01 -0.002 5.2E-02 -0.001 3.7E-01 0.000 8.7E-01 0.000 4.1E-01 t_Eubacterium_sp_3_1_31_unc strain eubacterium_sp_3_1_31_unclassified 201 3.2E-04 -0.001 1.9E-01 5.2E-01 -0.002 5.2E-02 -0.001 3.7E-01 0.000 8.7E-01 0.000 4.1E-01 k_10239 kingdom viruses 240 3.2E-03 -0.003 1.9E-01 3.5E-01 0.009 1.1E-02 0.004 6.9E-02 0.002 4.9E-01 0.000 9.0E-01 p_10239_noname phylum viruses_noname 240 3.2E-03 -0.003 1.9E-01 7.6E-01 0.009 1.1E-02 0.004 6.9E-02 0.002 4.9E-01 0.000 9.0E-01 c_10239_noname class viruses_noname 240 3.2E-03 -0.003 1.9E-01 8.1E-01 0.009 1.1E-02 0.004 6.9E-02 0.002 4.9E-01 0.000 9.0E-01 s_39496 species eubacterium_ventriosum 540 2.0E-03 0.001 1.9E-01 5.5E-01 -0.003 1.0E-01 -0.002 1.3E-01 -0.001 5.3E-01 -0.001 3.7E-01 t_GCF_000153885 strain gcf_000153885 540 2.0E-03 0.001 1.9E-01 5.2E-01 -0.003 1.0E-01 -0.002 1.3E-01 -0.001 5.3E-01 -0.001 3.7E-01 s_40518 species ruminococcus_bromii 587 2.5E-02 0.005 2.0E-01 5.5E-01 -0.013 6.2E-02 -0.003 5.4E-01 0.005 3.9E-01 -0.006 9.4E-02 t_GCF_000209875 strain gcf_000209875 587 2.5E-02 0.005 2.0E-01 5.2E-01 -0.013 6.2E-02 -0.003 5.4E-01 0.005 3.9E-01 -0.006 9.4E-02 s_1680 species bifidobacterium_adolescentis 319 8.8E-03 0.003 2.0E-01 5.5E-01 0.001 9.1E-01 -0.004 1.6E-01 -0.006 1.6E-01 -0.002 4.9E-01 t_Bifidobacterium_adolescen strain bifidobacterium_adolescentis_unclassified 319 8.8E-03 0.003 2.0E-01 5.2E-01 0.001 9.1E-01 -0.004 1.6E-01 -0.006 1.6E-01 -0.002 4.9E-01 f_171552 family prevotellaceae 405 4.1E-02 0.006 2.0E-01 5.4E-01 -0.010 2.4E-01 0.005 3.0E-01 -0.022 4.8E-03 0.000 9.5E-01 s_218538 species dialister_invisus 271 1.1E-02 -0.003 2.0E-01 5.5E-01 -0.011 3.2E-02 0.005 1.1E-01 -0.011 1.0E-02 -0.004 1.6E-01 t_GCF_000160055 strain gcf_000160055 271 1.1E-02 -0.003 2.0E-01 5.2E-01 -0.011 3.2E-02 0.005 1.1E-01 -0.011 1.0E-02 -0.004 1.6E-01 s_1343 species streptococcus_vestibularis 137 2.3E-04 -0.001 2.0E-01 5.5E-01 0.003 5.7E-04 0.002 5.7E-03 0.000 9.8E-01 -0.001 3.2E-01 t_Streptococcus_vestibulari strain streptococcus_vestibularis_unclassified 137 2.3E-04 -0.001 2.0E-01 5.2E-01 0.003 5.7E-04 0.002 5.7E-03 0.000 9.8E-01 -0.001 3.2E-01 f_171550 family rikenellaceae 907 6.9E-02 0.005 2.1E-01 5.4E-01 -0.011 9.7E-02 -0.004 3.4E-01 -0.005 3.8E-01 0.000 9.4E-01 g_239759 genus alistipes 907 6.9E-02 0.005 2.1E-01 6.0E-01 -0.011 9.7E-02 -0.004 3.4E-01 -0.005 3.8E-01 0.000 9.4E-01 s_658082 species lachnospiraceae_bacterium_2_1_58faa 259 4.3E-04 0.001 2.1E-01 5.6E-01 -0.003 6.1E-03 0.000 7.4E-01 -0.001 2.9E-01 0.001 2.8E-01 t_GCF_000218465 strain gcf_000218465 259 4.3E-04 0.001 2.1E-01 5.2E-01 -0.003 6.1E-03 0.000 7.4E-01 -0.001 2.9E-01 0.001 2.8E-01 s_469614 species erysipelotrichaceae_bacterium_6_1_45 307 9.5E-05 0.000 2.2E-01 5.6E-01 0.000 1.0E+00 0.000 9.6E-01 0.000 8.6E-01 0.000 7.5E-01 t_GCF_000242175 strain gcf_000242175 307 9.5E-05 0.000 2.2E-01 5.2E-01 0.000 1.0E+00 0.000 9.6E-01 0.000 8.6E-01 0.000 7.5E-01 s_310297 species bacteroides_plebeius 148 4.6E-03 -0.002 2.2E-01 5.6E-01 -0.001 6.7E-01 0.001 6.1E-01 0.003 1.4E-01 0.001 5.9E-01 t_GCF_000187895 strain gcf_000187895 148 4.6E-03 -0.002 2.2E-01 5.2E-01 -0.001 6.7E-01 0.001 6.1E-01 0.003 1.4E-01 0.001 5.9E-01 s_1288121 species alistipes_senegalensis 420 4.5E-04 0.001 2.2E-01 5.6E-01 0.000 8.3E-01 0.000 5.4E-01 -0.001 4.0E-01 0.000 4.8E-01 t_GCF_000312145 strain gcf_000312145 420 4.5E-04 0.001 2.2E-01 5.2E-01 0.000 8.3E-01 0.000 5.4E-01 -0.001 4.0E-01 0.000 4.8E-01 s_649756 species anaerostipes_hadrus 648 9.7E-04 0.001 2.2E-01 5.6E-01 0.003 6.1E-02 0.001 4.5E-01 0.001 3.2E-01 0.000 9.7E-01 t_GCF_000332875 strain gcf_000332875 648 9.7E-04 0.001 2.2E-01 5.2E-01 0.003 6.1E-02 0.001 4.5E-01 0.001 3.2E-01 0.000 9.7E-01 s_33039 species ruminococcus_torques 913 1.7E-02 0.002 2.3E-01 5.6E-01 -0.002 6.1E-01 -0.003 2.5E-01 0.003 3.1E-01 -0.001 7.5E-01 s_454155 species paraprevotella_xylaniphila 200 2.8E-04 0.000 2.3E-01 5.6E-01 -0.002 2.3E-02 0.000 6.2E-01 -0.001 1.0E-01 0.000 2.7E-01 t_GCF_000205165 strain gcf_000205165 200 2.8E-04 0.000 2.3E-01 5.3E-01 -0.002 2.3E-02 0.000 6.2E-01 -0.001 1.0E-01 0.000 2.7E-01 g_838 genus prevotella 243 3.6E-02 0.005 2.4E-01 6.7E-01 -0.007 4.2E-01 0.005 3.1E-01 -0.016 4.2E-02 0.001 8.5E-01 p_1224 phylum proteobacteria 897 2.4E-02 0.003 2.4E-01 7.6E-01 0.002 7.6E-01 0.003 4.1E-01 -0.004 4.0E-01 0.003 3.5E-01 s_40519 species ruminococcus_callidus 282 2.4E-03 -0.002 2.4E-01 5.8E-01 -0.002 3.6E-01 -0.001 7.3E-01 0.001 7.6E-01 -0.004 4.0E-03 t_GCF_000468015 strain gcf_000468015 282 2.4E-03 -0.002 2.4E-01 5.5E-01 -0.002 3.6E-01 -0.001 7.3E-01 0.001 7.6E-01 -0.004 4.0E-03 g_29465 genus veillonella 548 2.0E-03 -0.001 2.6E-01 6.7E-01 -0.001 6.9E-01 -0.001 7.2E-01 0.001 5.3E-01 -0.001 4.2E-01 s_28117 species alistipes_putredinis 742 3.4E-02 0.003 2.6E-01 6.0E-01 -0.016 2.9E-03 -0.006 6.2E-02 -0.008 7.5E-02 0.001 6.7E-01 t_GCF_000154465 strain gcf_000154465 742 3.4E-02 0.003 2.6E-01 5.7E-01 -0.016 2.9E-03 -0.006 6.2E-02 -0.008 7.5E-02 0.001 6.7E-01 f_186803 family lachnospiraceae 925 1.1E-01 0.004 2.7E-01 6.0E-01 0.000 9.9E-01 0.000 9.3E-01 0.009 8.2E-02 -0.002 5.4E-01 9

Supplementary Data 1a Taxonomi Non- Average Plasma TMAO Choline Choline Red meat Red meat Taxonomic ID Taxonomic label c type missing n Abundance Effect P FDR Effect P Effect P Effect P Effect P s_658081 species lachnospiraceae_bacterium_1_1_57faa 312 2.6E-03 -0.002 2.7E-01 6.1E-01 0.000 9.0E-01 -0.001 5.0E-01 0.001 6.6E-01 -0.001 5.3E-01 t_GCF_000218445 strain gcf_000218445 312 2.6E-03 -0.002 2.7E-01 5.7E-01 0.000 9.0E-01 -0.001 5.0E-01 0.001 6.6E-01 -0.001 5.3E-01 s_674529 species bacteroides_faecis 300 2.2E-03 0.001 2.7E-01 6.1E-01 -0.001 7.0E-01 0.000 6.5E-01 0.001 7.3E-01 0.000 8.3E-01 t_GCF_000226135 strain gcf_000226135 300 2.2E-03 0.001 2.7E-01 5.7E-01 -0.001 7.0E-01 0.000 6.5E-01 0.001 7.3E-01 0.000 8.3E-01 k_2 kingdom bacteria 925 9.9E-01 0.003 2.8E-01 3.5E-01 -0.010 2.5E-02 0.001 8.2E-01 -0.006 1.2E-01 0.003 2.2E-01 s_165179 species prevotella_copri 223 3.4E-02 0.005 2.9E-01 6.4E-01 -0.007 3.7E-01 0.005 3.1E-01 -0.015 4.5E-02 0.003 5.4E-01 t_GCF_000157935 strain gcf_000157935 223 3.4E-02 0.005 2.9E-01 6.0E-01 -0.007 3.7E-01 0.005 3.1E-01 -0.015 4.5E-02 0.003 5.4E-01 f_33958 family lactobacillaceae 172 1.2E-03 -0.001 2.9E-01 6.0E-01 -0.002 3.0E-01 0.000 7.6E-01 -0.005 4.4E-03 0.000 7.9E-01 g_872 genus desulfovibrio 303 5.5E-04 0.001 2.9E-01 7.3E-01 0.001 3.9E-01 0.000 6.4E-01 0.002 1.2E-01 -0.001 3.6E-01 c_526524 class erysipelotrichia 859 5.8E-03 -0.002 2.9E-01 8.1E-01 0.002 5.0E-01 0.000 8.3E-01 0.001 6.4E-01 0.002 3.0E-01 o_526525 order erysipelotrichales 859 5.8E-03 -0.002 2.9E-01 7.3E-01 0.002 5.0E-01 0.000 8.3E-01 0.001 6.4E-01 0.002 3.0E-01 f_128827 family erysipelotrichaceae 859 5.8E-03 -0.002 2.9E-01 6.0E-01 0.002 5.0E-01 0.000 8.3E-01 0.001 6.4E-01 0.002 3.0E-01 t_GCF_000154205 strain gcf_000154205 93 5.4E-03 -0.002 3.0E-01 6.0E-01 -0.003 3.9E-01 -0.001 6.8E-01 -0.008 1.9E-02 -0.003 1.9E-01 s_35833 species bilophila_wadsworthia 391 2.0E-04 0.000 3.0E-01 6.5E-01 -0.001 1.7E-01 0.000 8.6E-01 0.000 7.3E-01 -0.001 1.9E-01 t_GCF_000185705 strain gcf_000185705 391 2.0E-04 0.000 3.0E-01 6.0E-01 -0.001 1.7E-01 0.000 8.6E-01 0.000 7.3E-01 -0.001 1.9E-01 c_909932 class negativicutes 722 2.0E-02 -0.003 3.1E-01 8.1E-01 -0.013 2.1E-02 0.002 5.2E-01 -0.014 4.4E-03 -0.004 1.5E-01 o_909929 order selenomonadales 722 2.0E-02 -0.003 3.1E-01 7.3E-01 -0.013 2.1E-02 0.002 5.2E-01 -0.014 4.4E-03 -0.004 1.5E-01 s_28026 species bifidobacterium_pseudocatenulatum 129 1.1E-03 0.001 3.1E-01 6.5E-01 0.001 5.5E-01 0.000 9.8E-01 0.000 1.0E+00 -0.003 3.5E-03 t_GCF_000173435 strain gcf_000173435 129 1.1E-03 0.001 3.1E-01 6.1E-01 0.001 5.5E-01 0.000 9.8E-01 0.000 1.0E+00 -0.003 3.5E-03 g_1017280 genus pseudoflavonifractor 326 1.1E-04 0.000 3.1E-01 7.4E-01 0.000 4.7E-01 0.000 9.7E-01 0.000 9.9E-01 0.000 6.9E-01 s_106588 species pseudoflavonifractor_capillosus 326 1.1E-04 0.000 3.1E-01 6.5E-01 0.000 4.7E-01 0.000 9.7E-01 0.000 9.9E-01 0.000 6.9E-01 t_GCF_000169255 strain gcf_000169255 326 1.1E-04 0.000 3.1E-01 6.1E-01 0.000 4.7E-01 0.000 9.7E-01 0.000 9.9E-01 0.000 6.9E-01 s_283168_unclass species odoribacter_unclassified 234 4.5E-04 0.001 3.1E-01 6.5E-01 -0.002 1.4E-01 -0.001 4.6E-01 -0.002 4.8E-02 -0.001 1.5E-01 s_40545 species sutterella_wadsworthensis 199 2.7E-03 0.001 3.2E-01 6.5E-01 -0.002 5.2E-01 0.002 2.3E-01 0.000 9.2E-01 0.001 4.1E-01 s_876 species desulfovibrio_desulfuricans 255 2.7E-04 0.000 3.2E-01 6.5E-01 0.000 7.2E-01 -0.001 3.8E-02 0.001 1.5E-01 0.000 9.5E-01 g_2172 genus methanobrevibacter 395 5.0E-03 0.002 3.3E-01 7.4E-01 0.005 1.2E-01 -0.003 1.1E-01 0.003 2.7E-01 -0.002 2.5E-01 g_841 genus roseburia 919 2.7E-02 0.003 3.3E-01 7.4E-01 0.002 7.3E-01 -0.005 1.7E-01 0.008 6.7E-02 0.002 4.3E-01 k_2157 kingdom archaea 396 5.2E-03 0.002 3.5E-01 3.5E-01 0.005 1.4E-01 -0.003 8.7E-02 0.003 2.4E-01 -0.002 2.5E-01 p_28890 phylum euryarchaeota 396 5.2E-03 0.002 3.5E-01 7.6E-01 0.005 1.4E-01 -0.003 8.7E-02 0.003 2.4E-01 -0.002 2.5E-01 c_183925 class methanobacteria 396 5.2E-03 0.002 3.5E-01 8.1E-01 0.005 1.4E-01 -0.003 8.8E-02 0.003 2.3E-01 -0.002 2.5E-01 o_2158 order methanobacteriales 396 5.2E-03 0.002 3.5E-01 7.3E-01 0.005 1.4E-01 -0.003 8.8E-02 0.003 2.3E-01 -0.002 2.5E-01 f_2159 family methanobacteriaceae 396 5.2E-03 0.002 3.5E-01 6.0E-01 0.005 1.4E-01 -0.003 8.8E-02 0.003 2.3E-01 -0.002 2.5E-01 g_40544 genus sutterella 200 2.8E-03 0.001 3.5E-01 7.6E-01 -0.002 4.9E-01 0.002 2.5E-01 0.000 8.5E-01 0.001 3.9E-01 s_2173 species methanobrevibacter_smithii 381 4.3E-03 0.001 3.5E-01 7.0E-01 0.004 1.4E-01 -0.004 5.4E-02 0.003 3.2E-01 -0.002 1.7E-01 t_Methanobrevibacter_smithi strain methanobrevibacter_smithii_unclassified 381 4.3E-03 0.001 3.5E-01 6.8E-01 0.004 1.4E-01 -0.004 5.4E-02 0.003 3.2E-01 -0.002 1.7E-01 f_171549_noname family bacteroidales_noname 598 5.1E-03 0.001 3.7E-01 6.0E-01 -0.002 5.3E-01 0.000 8.5E-01 -0.001 5.7E-01 0.001 4.1E-01 g_171549_noname genus bacteroidales_noname 598 5.1E-03 0.001 3.7E-01 7.7E-01 -0.002 5.3E-01 0.000 8.5E-01 -0.001 5.7E-01 0.001 4.1E-01 s_1118061 species bacteroidales_bacterium_ph8 598 5.1E-03 0.001 3.7E-01 7.3E-01 -0.002 5.3E-01 0.000 8.5E-01 -0.001 5.7E-01 0.001 4.1E-01 t_GCF_000311925 strain gcf_000311925 598 5.1E-03 0.001 3.7E-01 7.0E-01 -0.002 5.3E-01 0.000 8.5E-01 -0.001 5.7E-01 0.001 4.1E-01 s_387661 species parabacteroides_johnsonii 222 1.9E-03 0.001 3.8E-01 7.3E-01 -0.001 7.7E-01 -0.001 3.6E-01 0.001 4.6E-01 0.000 9.2E-01 f_31957 family propionibacteriaceae 135 2.3E-04 0.000 3.8E-01 6.0E-01 -0.001 5.4E-01 0.000 8.2E-01 0.000 8.7E-01 -0.001 3.1E-01 f_10699 family siphoviridae 219 2.7E-03 -0.002 3.9E-01 6.0E-01 0.007 3.5E-02 0.002 4.7E-01 0.002 4.9E-01 -0.001 7.1E-01 g_1730 genus eubacterium 924 1.5E-01 -0.005 3.9E-01 7.8E-01 -0.011 2.4E-01 -0.012 5.6E-02 -0.018 1.8E-02 -0.006 2.7E-01 f_186806 family eubacteriaceae 924 1.5E-01 -0.005 3.9E-01 6.0E-01 -0.011 2.4E-01 -0.012 5.6E-02 -0.018 1.7E-02 -0.006 2.7E-01 s_186804_noname_unclass species peptostreptococcaceae_noname_unclassified 385 9.0E-04 -0.001 3.9E-01 7.5E-01 0.001 4.0E-01 0.001 2.1E-01 0.003 4.0E-02 0.000 6.6E-01 g_102106 genus collinsella 789 9.6E-03 -0.002 4.1E-01 7.8E-01 0.005 1.3E-01 0.001 5.4E-01 0.008 6.7E-03 0.003 1.1E-01 g_61170 genus holdemania 667 4.1E-04 0.000 4.2E-01 7.8E-01 0.001 3.1E-01 0.001 2.0E-01 0.002 4.4E-03 0.000 3.1E-01 f_541000 family ruminococcaceae 925 1.9E-01 0.003 4.2E-01 6.1E-01 0.002 7.5E-01 0.002 6.7E-01 0.013 2.6E-02 -0.007 1.0E-01 s_74426 species collinsella_aerofaciens 735 8.9E-03 -0.001 4.2E-01 7.9E-01 0.004 1.9E-01 0.001 6.8E-01 0.007 1.7E-02 0.003 1.6E-01 t_GCF_000169035 strain gcf_000169035 735 8.9E-03 -0.001 4.2E-01 7.8E-01 0.004 1.9E-01 0.001 6.8E-01 0.007 1.7E-02 0.003 1.6E-01 g_830 genus butyrivibrio 130 7.9E-03 0.002 4.3E-01 7.8E-01 -0.007 1.1E-01 0.006 4.2E-02 -0.003 5.3E-01 -0.006 2.1E-02 s_39777 species veillonella_atypica 199 3.4E-04 0.000 4.4E-01 8.0E-01 0.000 8.5E-01 0.000 8.1E-01 0.001 1.8E-01 -0.001 1.0E-01 t_Veillonella_atypica_uncla strain veillonella_atypica_unclassified 199 3.4E-04 0.000 4.4E-01 7.8E-01 0.000 8.5E-01 0.000 8.1E-01 0.001 1.8E-01 -0.001 1.0E-01 10

Supplementary Data 1a Taxonomi Non- Average Plasma TMAO Choline Choline Red meat Red meat Taxonomic ID Taxonomic label c type missing n Abundance Effect P FDR Effect P Effect P Effect P Effect P s_410072 species coprococcus_comes 751 5.3E-03 0.001 4.4E-01 8.0E-01 0.003 2.5E-01 0.000 8.0E-01 0.004 7.1E-02 -0.001 5.8E-01 t_GCF_000155875 strain gcf_000155875 751 5.3E-03 0.001 4.4E-01 7.8E-01 0.003 2.5E-01 0.000 8.0E-01 0.004 7.1E-02 -0.001 5.8E-01 s_45851 species butyrivibrio_crossotus 126 7.9E-03 0.002 4.4E-01 8.0E-01 -0.007 1.2E-01 0.006 4.7E-02 -0.002 5.4E-01 -0.006 2.0E-02 t_GCF_000156015 strain gcf_000156015 126 7.9E-03 0.002 4.4E-01 7.8E-01 -0.007 1.2E-01 0.006 4.7E-02 -0.002 5.4E-01 -0.006 2.0E-02 t_Bacteroides_ovatus_unclas strain bacteroides_ovatus_unclassified 852 1.3E-02 -0.002 4.4E-01 7.8E-01 -0.003 5.0E-01 -0.007 1.2E-02 -0.003 3.3E-01 0.000 8.6E-01 o_186826 order lactobacillales 821 1.1E-02 0.002 4.5E-01 7.3E-01 0.013 5.2E-03 0.004 2.4E-01 -0.001 7.9E-01 0.000 9.5E-01 c_91061 class bacilli 822 1.1E-02 0.002 4.6E-01 8.1E-01 0.013 5.4E-03 0.004 2.6E-01 -0.001 7.9E-01 0.000 9.6E-01 s_39491 species eubacterium_rectale 882 8.8E-02 -0.004 4.6E-01 8.1E-01 -0.020 3.9E-02 -0.019 4.6E-03 -0.022 9.1E-03 -0.008 1.5E-01 t_Eubacterium_rectale_uncla strain eubacterium_rectale_unclassified 882 8.8E-02 -0.004 4.6E-01 7.8E-01 -0.020 3.9E-02 -0.019 4.6E-03 -0.022 9.1E-03 -0.008 1.5E-01 s_1304 species streptococcus_salivarius 648 4.2E-03 0.001 4.7E-01 8.1E-01 0.008 1.2E-02 0.002 2.7E-01 0.001 7.5E-01 -0.001 4.6E-01 t_Streptococcus_salivarius_ strain streptococcus_salivarius_unclassified 648 4.2E-03 0.001 4.7E-01 7.8E-01 0.008 1.2E-02 0.002 2.7E-01 0.001 7.5E-01 -0.001 4.6E-01 s_751585 species coprococcus_sp_art55_1 150 8.6E-03 -0.002 4.8E-01 8.1E-01 -0.009 1.0E-01 0.005 1.4E-01 0.000 9.3E-01 -0.006 3.7E-02 t_GCF_000210595 strain gcf_000210595 150 8.6E-03 -0.002 4.8E-01 7.8E-01 -0.009 1.0E-01 0.005 1.4E-01 0.000 9.3E-01 -0.006 3.7E-02 t_Ruminococcus_obeum_unclas strain ruminococcus_obeum_unclassified 896 6.2E-03 -0.001 4.8E-01 7.8E-01 0.003 2.4E-01 0.000 9.7E-01 0.003 2.1E-01 0.002 2.9E-01 g_135858 genus catenibacterium 108 1.2E-03 0.000 4.8E-01 8.1E-01 0.003 1.8E-02 0.001 2.0E-01 0.000 9.5E-01 -0.001 3.2E-01 s_100886 species catenibacterium_mitsuokai 108 1.2E-03 0.000 4.8E-01 8.1E-01 0.003 1.8E-02 0.001 2.0E-01 0.000 9.5E-01 -0.001 3.2E-01 t_GCF_000173795 strain gcf_000173795 108 1.2E-03 0.000 4.8E-01 7.8E-01 0.003 1.8E-02 0.001 2.0E-01 0.000 9.5E-01 -0.001 3.2E-01 p_74201 phylum verrucomicrobia 644 2.2E-02 0.003 4.9E-01 7.6E-01 -0.001 8.8E-01 0.006 1.9E-01 0.009 1.4E-01 0.003 4.8E-01 c_203494 class verrucomicrobiae 644 2.2E-02 0.003 4.9E-01 8.1E-01 -0.001 8.8E-01 0.006 1.9E-01 0.009 1.4E-01 0.003 4.8E-01 o_48461 order verrucomicrobiales 644 2.2E-02 0.003 4.9E-01 7.3E-01 -0.001 8.8E-01 0.006 1.9E-01 0.009 1.4E-01 0.003 4.8E-01 f_203557 family verrucomicrobiaceae 644 2.2E-02 0.003 4.9E-01 6.8E-01 -0.001 8.8E-01 0.006 1.9E-01 0.009 1.4E-01 0.003 4.8E-01 g_239934 genus akkermansia 644 2.2E-02 0.003 4.9E-01 8.1E-01 -0.001 8.8E-01 0.006 1.9E-01 0.009 1.4E-01 0.003 4.8E-01 s_239935 species akkermansia_muciniphila 644 2.2E-02 0.003 4.9E-01 8.1E-01 -0.001 8.8E-01 0.006 1.9E-01 0.009 1.4E-01 0.003 4.8E-01 t_GCF_000020225 strain gcf_000020225 644 2.2E-02 0.003 4.9E-01 7.8E-01 -0.001 8.8E-01 0.006 1.9E-01 0.009 1.4E-01 0.003 4.8E-01 s_665950 species lachnospiraceae_bacterium_3_1_46faa 777 3.2E-03 0.001 5.0E-01 8.1E-01 -0.001 5.9E-01 -0.001 3.4E-01 0.000 8.0E-01 0.000 7.8E-01 t_GCF_000209405 strain gcf_000209405 777 3.2E-03 0.001 5.0E-01 7.8E-01 -0.001 5.9E-01 -0.001 3.4E-01 0.000 8.0E-01 0.000 7.8E-01 s_823 species parabacteroides_distasonis 613 7.2E-03 -0.001 5.0E-01 8.1E-01 -0.003 4.3E-01 0.003 1.5E-01 0.001 8.6E-01 -0.001 6.7E-01 t_Parabacteroides_distasoni strain parabacteroides_distasonis_unclassified 613 7.2E-03 -0.001 5.0E-01 7.8E-01 -0.003 4.3E-01 0.003 1.5E-01 0.001 8.6E-01 -0.001 6.7E-01 s_338188 species bacteroides_finegoldii 313 2.9E-03 0.001 5.0E-01 8.1E-01 -0.001 5.5E-01 0.000 8.2E-01 0.000 9.0E-01 0.003 2.4E-02 g_1348911 genus coprobacter 243 3.9E-04 0.000 5.0E-01 8.1E-01 -0.001 5.8E-01 0.001 3.6E-01 0.001 2.3E-01 -0.001 1.5E-01 s_1099853 species coprobacter_fastidiosus 243 3.9E-04 0.000 5.0E-01 8.1E-01 -0.001 5.8E-01 0.001 3.6E-01 0.001 2.3E-01 -0.001 1.5E-01 t_GCF_000473955 strain gcf_000473955 243 3.9E-04 0.000 5.0E-01 7.8E-01 -0.001 5.8E-01 0.001 3.6E-01 0.001 2.3E-01 -0.001 1.5E-01 g_577309 genus paraprevotella 259 5.1E-03 0.001 5.0E-01 8.1E-01 -0.005 7.8E-02 0.001 6.1E-01 -0.009 1.7E-04 0.000 9.6E-01 s_46503 species parabacteroides_merdae 681 1.2E-02 0.001 5.0E-01 8.1E-01 0.004 2.7E-01 0.001 5.2E-01 -0.002 4.5E-01 0.002 4.1E-01 t_Parabacteroides_merdae_un strain parabacteroides_merdae_unclassified 681 1.2E-02 0.001 5.0E-01 7.8E-01 0.004 2.7E-01 0.001 5.2E-01 -0.002 4.5E-01 0.002 4.1E-01 s_577309_unclass species paraprevotella_unclassified 259 3.3E-03 0.001 5.2E-01 8.2E-01 -0.003 1.7E-01 0.001 4.1E-01 -0.007 1.5E-04 0.000 6.8E-01 g_191303 genus turicibacter 160 2.1E-04 0.000 5.4E-01 8.1E-01 0.000 9.0E-01 0.000 8.0E-01 0.001 3.0E-01 0.000 8.1E-01 s_360807 species roseburia_inulinivorans 773 6.7E-03 0.001 5.5E-01 8.2E-01 0.000 9.2E-01 -0.002 4.1E-01 0.003 2.9E-01 0.001 6.7E-01 t_GCF_000174195 strain gcf_000174195 773 6.7E-03 0.001 5.5E-01 7.9E-01 0.000 9.2E-01 -0.002 4.1E-01 0.003 2.9E-01 0.001 6.7E-01 s_457412 species ruminococcus_sp_5_1_39bfaa 445 1.4E-02 -0.002 5.5E-01 8.2E-01 0.009 1.5E-01 0.001 7.5E-01 0.004 4.7E-01 -0.005 1.5E-01 t_GCF_000159975 strain gcf_000159975 445 1.4E-02 -0.002 5.5E-01 7.9E-01 0.009 1.5E-01 0.001 7.5E-01 0.004 4.7E-01 -0.005 1.5E-01 s_817 species bacteroides_fragilis 481 4.6E-03 -0.001 5.5E-01 8.2E-01 0.001 8.3E-01 0.000 8.6E-01 0.001 6.4E-01 0.000 9.7E-01 s_33038 species ruminococcus_gnavus 437 3.5E-03 -0.001 5.5E-01 8.2E-01 -0.005 1.3E-01 -0.002 2.8E-01 -0.001 7.2E-01 -0.002 3.7E-01 t_Ruminococcus_gnavus_uncla strain ruminococcus_gnavus_unclassified 437 3.5E-03 -0.001 5.5E-01 7.9E-01 -0.005 1.3E-01 -0.002 2.8E-01 -0.001 7.2E-01 -0.002 3.7E-01 s_371601 species bacteroides_xylanisolvens 650 2.0E-03 0.001 5.6E-01 8.2E-01 0.000 8.1E-01 -0.001 3.4E-01 0.000 9.3E-01 0.001 4.6E-01 t_Bacteroides_xylanisolvens strain bacteroides_xylanisolvens_unclassified 650 2.0E-03 0.001 5.6E-01 7.9E-01 0.000 8.1E-01 -0.001 3.4E-01 0.000 9.3E-01 0.001 4.6E-01 s_61171 species holdemania_filiformis 516 2.7E-04 0.000 5.6E-01 8.2E-01 0.001 4.8E-01 0.000 4.4E-01 0.002 1.4E-02 0.000 4.6E-01 t_GCF_000157995 strain gcf_000157995 516 2.7E-04 0.000 5.6E-01 7.9E-01 0.001 4.8E-01 0.000 4.4E-01 0.002 1.4E-02 0.000 4.6E-01 s_39492 species eubacterium_siraeum 633 3.0E-02 0.003 5.6E-01 8.2E-01 0.014 1.0E-01 0.004 4.3E-01 0.006 3.9E-01 0.004 3.5E-01 s_116085 species coprococcus_catus 642 1.3E-03 0.000 5.6E-01 8.2E-01 0.001 5.0E-01 0.000 7.1E-01 0.002 7.7E-02 -0.001 3.6E-01 t_GCF_000210555 strain gcf_000210555 642 1.3E-03 0.000 5.6E-01 7.9E-01 0.001 5.0E-01 0.000 7.1E-01 0.002 7.7E-02 -0.001 3.6E-01 t_Parabacteroides_johnsonii strain parabacteroides_johnsonii_unclassified 222 1.8E-03 0.001 5.7E-01 7.9E-01 0.002 3.0E-01 0.000 1.0E+00 0.001 4.9E-01 0.001 5.8E-01 g_244127 genus anaerotruncus 418 4.5E-04 0.000 5.7E-01 8.1E-01 0.000 9.9E-01 -0.001 4.4E-01 0.001 5.7E-01 0.000 8.4E-01 11

Supplementary Data 1a Taxonomi Non- Average Plasma TMAO Choline Choline Red meat Red meat Taxonomic ID Taxonomic label c type missing n Abundance Effect P FDR Effect P Effect P Effect P Effect P g_186532 genus c2likevirus 175 1.3E-03 -0.001 5.7E-01 8.1E-01 0.000 9.1E-01 0.001 5.5E-01 0.001 4.7E-01 -0.001 4.1E-01 c_186801 class clostridia 925 4.7E-01 0.003 5.7E-01 8.1E-01 -0.003 7.3E-01 -0.008 2.2E-01 0.004 6.2E-01 -0.011 5.8E-02 o_186802 order clostridiales 925 4.7E-01 0.003 5.7E-01 7.3E-01 -0.003 7.3E-01 -0.008 2.2E-01 0.004 6.2E-01 -0.011 5.8E-02 t_Faecalibacterium_prausnit strain faecalibacterium_prausnitzii_unclassified 904 5.9E-02 -0.002 5.7E-01 7.9E-01 -0.007 2.2E-01 0.001 8.1E-01 -0.002 6.8E-01 -0.003 3.1E-01 g_541000_noname genus ruminococcaceae_noname 406 7.7E-04 0.000 5.7E-01 8.1E-01 0.000 7.9E-01 0.000 1.0E+00 0.000 9.1E-01 -0.001 2.6E-01 s_552398 species ruminococcaceae_bacterium_d16 406 7.7E-04 0.000 5.7E-01 8.2E-01 0.000 7.9E-01 0.000 1.0E+00 0.000 9.1E-01 -0.001 2.6E-01 t_GCF_000177015 strain gcf_000177015 406 7.7E-04 0.000 5.7E-01 7.9E-01 0.000 7.9E-01 0.000 1.0E+00 0.000 9.1E-01 -0.001 2.6E-01 o_28883 order caudovirales 238 2.9E-03 -0.001 5.8E-01 7.3E-01 0.008 1.5E-02 0.002 3.7E-01 0.002 4.3E-01 -0.001 7.1E-01 s_904_unclass species acidaminococcus_unclassified 119 1.5E-03 0.000 5.9E-01 8.3E-01 -0.001 6.0E-01 -0.001 1.6E-01 -0.002 1.1E-01 0.000 6.5E-01 g_724 genus haemophilus 335 1.2E-03 -0.001 5.9E-01 8.1E-01 -0.003 1.3E-01 0.001 5.2E-01 -0.001 5.7E-01 -0.001 2.9E-01 o_85004 order bifidobacteriales 656 2.0E-02 -0.002 5.9E-01 7.3E-01 0.012 6.9E-02 -0.010 2.1E-02 -0.005 4.1E-01 -0.008 3.9E-02 f_31953 family bifidobacteriaceae 656 2.0E-02 -0.002 5.9E-01 7.1E-01 0.012 6.9E-02 -0.010 2.1E-02 -0.005 4.1E-01 -0.008 3.9E-02 s_291645 species bacteroides_nordii 188 3.0E-04 0.000 6.0E-01 8.4E-01 0.000 8.7E-01 0.000 5.5E-01 0.001 5.0E-01 0.000 3.8E-01 t_GCF_000273175 strain gcf_000273175 188 3.0E-04 0.000 6.0E-01 8.1E-01 0.000 8.7E-01 0.000 5.5E-01 0.001 5.0E-01 0.000 3.8E-01 g_1678 genus bifidobacterium 654 2.0E-02 -0.002 6.0E-01 8.1E-01 0.012 6.8E-02 -0.010 2.1E-02 -0.005 4.1E-01 -0.008 4.0E-02 p_1239 phylum firmicutes 925 5.1E-01 0.003 6.0E-01 7.6E-01 0.000 9.6E-01 -0.003 6.6E-01 -0.001 9.1E-01 -0.012 4.2E-02 g_644652 genus gordonibacter 403 3.2E-04 0.000 6.0E-01 8.1E-01 -0.001 3.3E-01 0.000 9.4E-01 0.000 7.5E-01 -0.001 1.9E-01 s_471189 species gordonibacter_pamelaeae 403 3.2E-04 0.000 6.0E-01 8.4E-01 -0.001 3.3E-01 0.000 9.4E-01 0.000 7.5E-01 -0.001 1.9E-01 t_GCF_000210055 strain gcf_000210055 403 3.2E-04 0.000 6.0E-01 8.2E-01 -0.001 3.3E-01 0.000 9.4E-01 0.000 7.5E-01 -0.001 1.9E-01 f_1300 family streptococcaceae 807 9.3E-03 0.001 6.1E-01 7.1E-01 0.011 9.2E-03 0.004 2.0E-01 -0.001 8.4E-01 0.000 9.5E-01 s_665951 species lachnospiraceae_bacterium_8_1_57faa 326 1.8E-03 0.001 6.2E-01 8.5E-01 -0.002 4.6E-01 -0.002 2.6E-01 0.000 9.5E-01 -0.002 2.2E-01 t_GCF_000185545 strain gcf_000185545 326 1.8E-03 0.001 6.2E-01 8.2E-01 -0.002 4.6E-01 -0.002 2.6E-01 0.000 9.5E-01 -0.002 2.2E-01 s_729 species haemophilus_parainfluenzae 333 1.1E-03 0.000 6.2E-01 8.5E-01 -0.003 1.3E-01 0.001 5.8E-01 -0.001 5.5E-01 -0.001 2.8E-01 t_Haemophilus_parainfluenza strain haemophilus_parainfluenzae_unclassified 333 1.1E-03 0.000 6.2E-01 8.2E-01 -0.003 1.3E-01 0.001 5.8E-01 -0.001 5.5E-01 -0.001 2.8E-01 g_33042 genus coprococcus 814 2.0E-02 -0.001 6.3E-01 8.3E-01 -0.001 8.5E-01 0.003 3.5E-01 0.006 2.4E-01 -0.004 1.8E-01 o_135625 order pasteurellales 335 1.2E-03 0.000 6.3E-01 7.3E-01 -0.003 1.5E-01 0.001 5.2E-01 -0.001 5.6E-01 -0.001 3.1E-01 f_712 family pasteurellaceae 335 1.2E-03 0.000 6.3E-01 7.1E-01 -0.003 1.5E-01 0.001 5.2E-01 -0.001 5.6E-01 -0.001 3.1E-01 s_61170_unclass species holdemania_unclassified 390 1.3E-04 0.000 6.3E-01 8.5E-01 0.000 5.0E-01 0.000 5.3E-01 0.000 3.7E-01 0.000 1.4E-01 s_454154 species paraprevotella_clara 236 1.6E-03 0.000 6.4E-01 8.5E-01 -0.003 4.5E-02 0.000 6.8E-01 -0.005 4.5E-04 0.000 8.1E-01 t_GCF_000233955 strain gcf_000233955 236 1.6E-03 0.000 6.4E-01 8.3E-01 -0.003 4.5E-02 0.000 6.8E-01 -0.005 4.5E-04 0.000 8.1E-01 o_2037 order actinomycetales 246 2.8E-04 0.000 6.4E-01 7.3E-01 -0.001 5.4E-01 0.000 9.7E-01 0.000 5.5E-01 -0.001 2.5E-01 o_91347 order enterobacteriales 551 1.5E-02 0.001 6.4E-01 7.3E-01 0.004 4.1E-01 0.000 9.6E-01 -0.006 2.1E-01 0.002 5.7E-01 f_543 family enterobacteriaceae 551 1.5E-02 0.001 6.4E-01 7.1E-01 0.004 4.1E-01 0.000 9.6E-01 -0.006 2.1E-01 0.002 5.7E-01 t_Clostridium_bolteae_uncla strain clostridium_bolteae_unclassified 360 3.0E-04 0.000 6.5E-01 8.3E-01 -0.003 2.5E-03 0.000 6.5E-01 0.000 5.8E-01 0.000 9.2E-01 t_Eubacterium_siraeum_uncla strain eubacterium_siraeum_unclassified 625 2.8E-02 0.002 6.5E-01 8.3E-01 0.015 6.3E-02 0.005 3.7E-01 0.006 3.5E-01 0.006 1.9E-01 s_562 species escherichia_coli 398 1.1E-02 -0.001 6.6E-01 8.7E-01 0.001 7.9E-01 0.002 6.3E-01 -0.005 3.0E-01 0.001 8.4E-01 t_Escherichia_coli_unclassi strain escherichia_coli_unclassified 398 1.1E-02 -0.001 6.6E-01 8.3E-01 0.001 7.9E-01 0.002 6.3E-01 -0.005 3.0E-01 0.001 8.4E-01 s_39490 species eubacterium_ramulus 645 2.3E-03 0.000 6.6E-01 8.7E-01 0.001 7.5E-01 0.000 8.1E-01 0.001 6.1E-01 0.000 8.1E-01 t_GCF_000469345 strain gcf_000469345 645 2.3E-03 0.000 6.6E-01 8.3E-01 0.001 7.5E-01 0.000 8.1E-01 0.001 6.1E-01 0.000 8.1E-01 s_28118 species odoribacter_splanchnicus 464 3.8E-03 -0.001 6.7E-01 8.7E-01 -0.001 7.4E-01 0.003 8.2E-02 0.003 1.5E-01 0.003 4.5E-02 t_GCF_000190535 strain gcf_000190535 464 3.8E-03 -0.001 6.7E-01 8.3E-01 -0.001 7.4E-01 0.003 8.2E-02 0.003 1.5E-01 0.003 4.5E-02 g_561 genus escherichia 518 1.2E-02 -0.001 6.7E-01 8.7E-01 0.003 5.5E-01 0.001 7.7E-01 -0.003 4.7E-01 0.000 8.8E-01 s_841_unclass species roseburia_unclassified 236 1.6E-03 -0.001 6.8E-01 8.7E-01 0.000 9.3E-01 0.002 1.1E-01 0.000 8.2E-01 -0.001 3.2E-01 o_84999 order coriobacteriales 915 1.3E-02 0.001 6.8E-01 7.3E-01 0.005 8.4E-02 0.003 1.8E-01 0.005 3.5E-02 0.002 2.6E-01 f_84107 family coriobacteriaceae 915 1.3E-02 0.001 6.8E-01 7.1E-01 0.005 8.4E-02 0.003 1.8E-01 0.005 3.5E-02 0.002 2.6E-01 f_186804 family peptostreptococcaceae 458 1.3E-03 0.000 6.8E-01 7.1E-01 0.003 8.8E-02 0.002 9.7E-02 0.002 1.7E-01 0.000 8.7E-01 c_28221 class deltaproteobacteria 707 3.2E-03 0.000 6.8E-01 8.1E-01 -0.001 6.0E-01 0.001 7.2E-01 0.003 6.7E-02 0.001 3.7E-01 o_213115 order desulfovibrionales 707 3.2E-03 0.000 6.8E-01 7.3E-01 -0.001 6.0E-01 0.001 7.2E-01 0.003 6.7E-02 0.001 3.7E-01 f_194924 family desulfovibrionaceae 707 3.2E-03 0.000 6.8E-01 7.1E-01 -0.001 6.0E-01 0.001 7.2E-01 0.003 6.7E-02 0.001 3.7E-01 s_40520 species ruminococcus_obeum 899 7.0E-03 -0.001 7.0E-01 8.8E-01 0.004 1.9E-01 0.001 6.6E-01 0.003 2.0E-01 0.002 1.8E-01 s_1318 species streptococcus_parasanguinis 492 1.7E-03 0.000 7.0E-01 8.8E-01 0.004 6.6E-02 0.001 4.5E-01 0.002 2.8E-01 -0.001 3.0E-01 t_Streptococcus_parasanguin strain streptococcus_parasanguinis_unclassified 492 1.7E-03 0.000 7.0E-01 8.6E-01 0.004 6.6E-02 0.001 4.5E-01 0.002 2.8E-01 -0.001 3.0E-01 s_186532_unclass species c2likevirus_unclassified 173 1.2E-03 -0.001 7.0E-01 8.8E-01 0.001 8.0E-01 0.001 3.8E-01 0.001 6.2E-01 0.000 1.0E+00 12

Supplementary Data 1a Taxonomi Non- Average Plasma TMAO Choline Choline Red meat Red meat Taxonomic ID Taxonomic label c type missing n Abundance Effect P FDR Effect P Effect P Effect P Effect P s_191303_unclass species turicibacter_unclassified 148 1.3E-04 0.000 7.1E-01 8.8E-01 0.000 9.5E-01 0.000 7.7E-01 0.001 2.4E-01 0.000 9.1E-01 g_186803_noname genus lachnospiraceae_noname 912 1.1E-02 0.001 7.1E-01 8.9E-01 -0.001 6.7E-01 -0.004 1.2E-01 0.002 4.0E-01 -0.002 3.2E-01 s_46506 species bacteroides_stercoris 520 2.5E-02 -0.001 7.2E-01 8.8E-01 -0.009 1.1E-01 0.001 8.4E-01 0.004 4.4E-01 0.007 2.3E-02 t_Desulfovibrio_desulfurica strain desulfovibrio_desulfuricans_unclassified 251 2.4E-04 0.000 7.2E-01 8.8E-01 -0.001 1.8E-01 -0.001 3.9E-02 0.000 7.8E-01 0.000 9.7E-01 s_189330_unclass species dorea_unclassified 114 3.8E-04 0.000 7.3E-01 8.9E-01 0.001 4.6E-01 0.002 4.1E-02 0.000 6.1E-01 -0.001 4.0E-01 t_Bacteroides_fragilis_uncl strain bacteroides_fragilis_unclassified 478 4.4E-03 -0.001 7.5E-01 8.8E-01 0.001 6.4E-01 0.001 6.2E-01 0.003 3.1E-01 0.000 9.6E-01 t_Sutterella_wadsworthensis strain sutterella_wadsworthensis_unclassified 152 1.9E-03 0.000 7.5E-01 8.8E-01 -0.002 3.2E-01 0.001 3.8E-01 0.001 6.1E-01 0.000 7.7E-01 g_100883 genus coprobacillus 243 6.5E-04 0.000 7.5E-01 9.3E-01 -0.001 6.9E-01 -0.001 1.6E-01 0.002 1.5E-01 0.000 8.4E-01 s_100883_unclass species coprobacillus_unclassified 243 6.5E-04 0.000 7.5E-01 9.0E-01 -0.001 6.9E-01 -0.001 1.6E-01 0.002 1.5E-01 0.000 8.4E-01 p_976 phylum bacteroidetes 925 4.0E-01 -0.002 7.5E-01 7.6E-01 -0.022 2.6E-02 0.000 9.6E-01 -0.004 6.4E-01 0.012 3.3E-02 c_200643 class bacteroidia 925 4.0E-01 -0.002 7.5E-01 8.1E-01 -0.022 2.6E-02 0.000 9.6E-01 -0.004 6.4E-01 0.012 3.4E-02 o_171549 order bacteroidales 925 4.0E-01 -0.002 7.5E-01 7.5E-01 -0.022 2.6E-02 0.000 9.6E-01 -0.004 6.4E-01 0.012 3.4E-02 s_28111 species bacteroides_eggerthii 258 1.7E-02 0.001 7.5E-01 9.0E-01 -0.014 1.2E-02 -0.005 1.2E-01 -0.004 4.0E-01 -0.002 3.8E-01 t_Bacteroides_eggerthii_unc strain bacteroides_eggerthii_unclassified 258 1.7E-02 0.001 7.5E-01 8.8E-01 -0.014 1.2E-02 -0.005 1.2E-01 -0.004 4.0E-01 -0.002 3.8E-01 s_166486 species roseburia_intestinalis 724 1.3E-02 -0.001 7.6E-01 9.0E-01 0.007 2.0E-01 -0.005 1.3E-01 0.009 4.6E-02 0.003 2.6E-01 t_Roseburia_intestinalis_un strain roseburia_intestinalis_unclassified 724 1.3E-02 -0.001 7.6E-01 8.8E-01 0.007 2.0E-01 -0.005 1.3E-01 0.009 4.6E-02 0.003 2.6E-01 t_Bacteroides_stercoris_unc strain bacteroides_stercoris_unclassified 520 2.5E-02 -0.001 7.6E-01 8.8E-01 -0.010 7.9E-02 0.000 9.3E-01 0.005 3.3E-01 0.006 4.1E-02 p_201174 phylum actinobacteria 918 3.4E-02 -0.001 7.6E-01 7.6E-01 0.017 8.7E-03 -0.004 3.6E-01 0.002 7.4E-01 -0.005 1.5E-01 c_1760 class actinobacteria 918 3.4E-02 -0.001 7.6E-01 8.1E-01 0.017 8.7E-03 -0.004 3.6E-01 0.002 7.4E-01 -0.005 1.5E-01 s_113107 species streptococcus_australis 268 2.8E-04 0.000 7.7E-01 9.0E-01 0.002 5.6E-02 0.001 9.9E-02 0.002 1.4E-02 0.001 2.6E-01 t_Streptococcus_australis_u strain streptococcus_australis_unclassified 268 2.8E-04 0.000 7.7E-01 8.8E-01 0.002 5.6E-02 0.001 9.9E-02 0.002 1.4E-02 0.001 2.6E-01 s_2172_unclass species methanobrevibacter_unclassified 296 7.4E-04 0.000 7.7E-01 9.0E-01 0.002 1.1E-01 -0.001 6.3E-01 0.001 4.2E-01 0.000 8.6E-01 g_1301 genus streptococcus 788 9.0E-03 0.001 7.7E-01 9.3E-01 0.011 1.3E-02 0.003 2.8E-01 -0.001 8.4E-01 0.000 9.8E-01 s_239759_unclass species alistipes_unclassified 122 2.9E-03 0.000 7.8E-01 9.0E-01 0.003 2.8E-01 0.003 1.4E-01 0.006 3.0E-02 0.002 1.4E-01 t_GCF_000162015 strain gcf_000162015 293 8.7E-03 0.001 7.8E-01 8.9E-01 0.009 9.1E-02 0.007 5.5E-02 0.002 7.2E-01 0.003 3.5E-01 s_1535 species clostridium_leptum 692 2.6E-03 0.000 7.9E-01 9.0E-01 0.002 4.9E-01 -0.004 3.6E-02 0.001 4.6E-01 0.000 8.6E-01 t_GCF_000154345 strain gcf_000154345 692 2.6E-03 0.000 7.9E-01 8.9E-01 0.002 4.9E-01 -0.004 3.6E-02 0.001 4.6E-01 0.000 8.6E-01 g_283168 genus odoribacter 706 6.4E-03 0.000 7.9E-01 9.3E-01 0.000 1.0E+00 0.004 2.8E-02 0.001 6.9E-01 0.002 1.7E-01 s_169435 species anaerotruncus_colihominis 228 1.1E-04 0.000 8.0E-01 9.2E-01 0.000 6.4E-01 0.001 1.3E-01 0.000 4.1E-01 0.000 6.9E-01 t_GCF_000154565 strain gcf_000154565 228 1.1E-04 0.000 8.0E-01 9.0E-01 0.000 6.4E-01 0.001 1.3E-01 0.000 4.1E-01 0.000 6.9E-01 c_1236 class gammaproteobacteria 681 1.6E-02 0.001 8.1E-01 8.1E-01 0.001 9.2E-01 0.001 6.6E-01 -0.008 1.0E-01 0.001 8.4E-01 g_577310 genus parasutterella 420 5.9E-04 0.000 8.3E-01 9.5E-01 -0.002 8.7E-02 0.000 8.2E-01 -0.002 2.1E-02 0.000 3.8E-01 s_487175 species parasutterella_excrementihominis 420 5.9E-04 0.000 8.3E-01 9.3E-01 -0.002 8.7E-02 0.000 8.2E-01 -0.002 2.1E-02 0.000 3.8E-01 t_GCF_000205025 strain gcf_000205025 420 5.9E-04 0.000 8.3E-01 9.1E-01 -0.002 8.7E-02 0.000 8.2E-01 -0.002 2.1E-02 0.000 3.8E-01 t_Bacteroides_finegoldii_un strain bacteroides_finegoldii_unclassified 298 2.2E-03 0.000 8.3E-01 9.1E-01 -0.002 4.1E-01 0.001 3.0E-01 -0.001 5.7E-01 0.001 2.6E-01 g_216851 genus faecalibacterium 915 7.2E-02 -0.001 8.4E-01 9.5E-01 -0.001 8.6E-01 0.004 3.1E-01 0.002 7.4E-01 -0.002 5.9E-01 s_853 species faecalibacterium_prausnitzii 915 7.2E-02 -0.001 8.4E-01 9.3E-01 -0.001 8.6E-01 0.004 3.1E-01 0.002 7.4E-01 -0.002 5.9E-01 s_29466 species veillonella_parvula 322 3.6E-04 0.000 8.4E-01 9.3E-01 -0.001 2.8E-01 -0.001 4.1E-01 -0.001 2.2E-01 -0.001 1.8E-01 t_Veillonella_parvula_uncla strain veillonella_parvula_unclassified 322 3.6E-04 0.000 8.4E-01 9.1E-01 -0.001 2.8E-01 -0.001 4.1E-01 -0.001 2.2E-01 -0.001 1.8E-01 s_658089 species lachnospiraceae_bacterium_5_1_63faa 779 1.5E-03 0.000 8.4E-01 9.3E-01 0.002 3.2E-01 0.001 5.7E-01 0.000 9.7E-01 -0.001 1.8E-01 t_GCF_000185525 strain gcf_000185525 779 1.5E-03 0.000 8.4E-01 9.1E-01 0.002 3.2E-01 0.001 5.7E-01 0.000 9.7E-01 -0.001 1.8E-01 s_47678 species bacteroides_caccae 588 1.1E-02 0.000 8.5E-01 9.3E-01 -0.006 1.4E-01 -0.001 8.3E-01 0.005 1.7E-01 0.002 4.6E-01 t_Bacteroides_caccae_unclas strain bacteroides_caccae_unclassified 588 1.1E-02 0.000 8.5E-01 9.1E-01 -0.006 1.4E-01 -0.001 8.3E-01 0.005 1.7E-01 0.002 4.6E-01 s_33043 species coprococcus_eutactus 117 4.4E-03 0.000 8.6E-01 9.3E-01 0.002 5.2E-01 -0.002 4.0E-01 0.002 4.7E-01 0.000 9.7E-01 t_GCF_000154425 strain gcf_000154425 117 4.4E-03 0.000 8.6E-01 9.1E-01 0.002 5.2E-01 -0.002 4.0E-01 0.002 4.7E-01 0.000 9.7E-01 g_572511 genus blautia 919 2.8E-02 0.000 8.6E-01 9.6E-01 -0.004 3.2E-01 -0.005 1.2E-01 0.002 5.2E-01 0.000 8.9E-01 s_1308 species streptococcus_thermophilus 452 2.0E-03 0.000 8.6E-01 9.3E-01 0.000 9.7E-01 -0.002 3.6E-01 -0.004 7.9E-02 0.000 8.1E-01 t_Streptococcus_thermophilu strain streptococcus_thermophilus_unclassified 452 2.0E-03 0.000 8.6E-01 9.1E-01 0.000 9.7E-01 -0.002 3.6E-01 -0.004 7.9E-02 0.000 8.1E-01 s_35832_unclass species bilophila_unclassified 673 2.5E-03 0.000 8.8E-01 9.3E-01 -0.002 3.6E-01 0.000 7.3E-01 0.002 2.8E-01 0.001 3.3E-01 s_53443 species blautia_hydrogenotrophica 263 2.8E-04 0.000 8.8E-01 9.3E-01 0.000 6.9E-01 0.000 9.8E-01 -0.001 1.6E-01 -0.001 2.8E-01 t_GCF_000157975 strain gcf_000157975 263 2.8E-04 0.000 8.8E-01 9.2E-01 0.000 6.9E-01 0.000 9.8E-01 -0.001 1.6E-01 -0.001 2.8E-01 f_171551 family porphyromonadaceae 912 4.7E-02 0.000 8.8E-01 8.8E-01 0.002 6.7E-01 0.006 8.4E-02 -0.002 7.1E-01 0.004 2.1E-01 s_561_unclass species escherichia_unclassified 344 6.2E-04 0.000 9.0E-01 9.4E-01 0.001 4.6E-01 -0.001 3.9E-01 0.001 2.9E-01 -0.001 5.4E-01 13

Supplementary Data 1b Supplementary Data 1b. Microbial associations with TMAO in 8 sensitivity analysis models. Basic model included basic necessary variables including age, antibiotics use, probiotics use, the Bristol Stool Chart, and/or fish intake (for non-fish dietary variables). Full model (MV; used in Supplementary Data 1a) was based on basic model and further adjusted for BMI, physical activity, energy intake, smoking, cumulative dietary quality. DM, diabetes mellitus. MV + renal function MV + pre-DM and MV & Exclude DM MV + FFQ MV + DDR (5d avg) MV + DDR (2d avg) Taxonom Basic Model MV + HBA1c Taxonomic label indicator DM status patients phosphorus intake phosphorus intake phosphorus intake ic type Effect P FDR Effect P FDR Effect P FDR Effect P FDR Effect P FDR Effect P FDR Effect P FDR Effect P FDR gcf_000173975 strain 0.0059 3.7E-04 1.1E-02 0.0061 3.0E-04 1.8E-02 0.0061 3.2E-04 1.9E-02 0.0060 4.0E-04 1.6E-02 0.0061 3.8E-04 1.3E-02 0.0066 1.3E-04 1.6E-02 0.0059 4.5E-04 1.5E-02 0.0060 3.8E-04 1.6E-02 eubacterium_hallii species 0.0059 3.7E-04 1.0E-02 0.0061 3.0E-04 1.4E-02 0.0061 3.2E-04 1.6E-02 0.0060 4.0E-04 1.5E-02 0.0061 3.8E-04 1.5E-02 0.0066 1.3E-04 1.0E-02 0.0059 4.5E-04 1.3E-02 0.0060 3.8E-04 1.4E-02 gcf_000210575 strain 0.0062 2.8E-04 1.1E-02 0.0062 4.0E-04 1.8E-02 0.0056 1.4E-03 2.5E-02 0.0060 6.3E-04 1.6E-02 0.0062 4.5E-04 1.3E-02 0.0059 9.7E-04 2.3E-02 0.0061 4.7E-04 1.5E-02 0.0061 4.8E-04 1.6E-02 alistipes_shahii species 0.0062 2.8E-04 1.0E-02 0.0062 4.0E-04 1.4E-02 0.0056 1.4E-03 2.2E-02 0.0060 6.3E-04 1.5E-02 0.0062 4.5E-04 1.5E-02 0.0059 9.7E-04 2.3E-02 0.0061 4.7E-04 1.3E-02 0.0061 4.8E-04 1.4E-02 eggerthella_unclassified species 0.0020 3.2E-03 5.0E-02 0.0025 4.5E-04 1.4E-02 0.0023 9.8E-04 2.0E-02 0.0022 2.0E-03 3.1E-02 0.0022 1.5E-03 3.2E-02 0.0023 1.3E-03 2.3E-02 0.0022 1.6E-03 2.5E-02 0.0021 2.3E-03 3.5E-02 clostridium_clostridioforme species 0.0013 1.7E-04 1.0E-02 0.0012 4.9E-04 1.4E-02 0.0012 3.9E-04 1.6E-02 0.0012 3.5E-04 1.5E-02 0.0011 1.6E-03 3.2E-02 0.0013 1.5E-04 1.0E-02 0.0012 2.6E-04 1.3E-02 0.0012 3.5E-04 1.4E-02 gcf_000225345 strain 0.0063 3.3E-04 1.1E-02 0.0062 5.4E-04 1.8E-02 0.0061 7.5E-04 2.0E-02 0.0062 5.4E-04 1.6E-02 0.0067 2.3E-04 1.3E-02 0.0061 9.3E-04 2.3E-02 0.0061 7.4E-04 1.8E-02 0.0061 6.7E-04 1.7E-02 roseburia_hominis species 0.0063 3.3E-04 1.0E-02 0.0062 5.4E-04 1.4E-02 0.0061 7.5E-04 1.9E-02 0.0062 5.4E-04 1.5E-02 0.0067 2.3E-04 1.5E-02 0.0061 9.3E-04 2.3E-02 0.0061 7.4E-04 1.7E-02 0.0061 6.7E-04 1.6E-02 gcf_000155435 strain 0.0010 4.9E-04 1.2E-02 0.0010 5.9E-04 1.8E-02 0.0011 2.2E-04 1.9E-02 0.0011 3.6E-04 1.6E-02 0.0011 4.9E-04 1.3E-02 0.0010 1.7E-03 2.3E-02 0.0011 2.4E-04 1.5E-02 0.0011 3.9E-04 1.6E-02 clostridiales_bacterium_1_7_47faa species 0.0010 4.9E-04 1.1E-02 0.0010 5.9E-04 1.4E-02 0.0011 2.2E-04 1.6E-02 0.0011 3.6E-04 1.5E-02 0.0011 4.9E-04 1.5E-02 0.0010 1.7E-03 2.3E-02 0.0011 2.4E-04 1.3E-02 0.0011 3.9E-04 1.4E-02 gcf_000233455 strain 0.0008 6.7E-04 1.4E-02 0.0007 1.2E-03 2.9E-02 0.0008 8.2E-04 2.0E-02 0.0008 8.5E-04 1.7E-02 0.0007 2.3E-03 4.0E-02 0.0007 1.7E-03 2.3E-02 0.0008 8.6E-04 1.8E-02 0.0007 1.1E-03 2.3E-02 clostridium_citroniae species 0.0008 6.7E-04 1.3E-02 0.0007 1.2E-03 2.3E-02 0.0008 8.2E-04 1.9E-02 0.0008 8.5E-04 1.7E-02 0.0007 2.3E-03 3.6E-02 0.0007 1.7E-03 2.3E-02 0.0008 8.6E-04 1.7E-02 0.0007 1.1E-03 2.2E-02 gcf_000242195 strain 0.0007 2.7E-03 4.2E-02 0.0007 1.7E-03 3.4E-02 0.0007 1.1E-03 2.3E-02 0.0007 1.8E-03 3.2E-02 0.0007 1.8E-03 3.7E-02 0.0007 1.8E-03 2.3E-02 0.0007 1.6E-03 2.5E-02 0.0007 1.8E-03 3.1E-02 erysipelotrichaceae_bacterium_21_3 species 0.0007 2.7E-03 4.8E-02 0.0007 1.7E-03 2.9E-02 0.0007 1.1E-03 2.0E-02 0.0007 1.8E-03 3.1E-02 0.0007 1.8E-03 3.2E-02 0.0007 1.8E-03 2.3E-02 0.0007 1.6E-03 2.5E-02 0.0007 1.8E-03 3.1E-02 gcf_000156035 strain -0.0033 1.1E-04 1.1E-02 -0.0027 2.1E-03 3.5E-02 -0.0031 4.6E-04 1.9E-02 -0.0031 4.3E-04 1.6E-02 -0.0031 5.3E-04 1.3E-02 -0.0031 5.7E-04 2.3E-02 -0.0031 4.7E-04 1.5E-02 -0.0030 5.1E-04 1.6E-02 clostridium_nexile species -0.0033 1.1E-04 1.0E-02 -0.0027 2.1E-03 3.2E-02 -0.0031 4.6E-04 1.6E-02 -0.0031 4.3E-04 1.5E-02 -0.0031 5.3E-04 1.5E-02 -0.0031 5.7E-04 2.3E-02 -0.0031 4.7E-04 1.3E-02 -0.0030 5.1E-04 1.4E-02 sutterellaceae_unclassified genus 0.0023 4.5E-03 2.6E-01 0.0026 2.2E-03 8.4E-02 0.0028 8.9E-04 5.2E-02 0.0026 1.7E-03 9.7E-02 0.0028 9.1E-04 5.3E-02 0.0023 6.3E-03 2.0E-01 0.0026 2.1E-03 1.2E-01 0.0026 2.0E-03 1.2E-01 gcf_000156655 strain -0.0031 1.1E-02 1.1E-01 -0.0037 2.3E-03 3.5E-02 -0.0036 3.6E-03 4.4E-02 -0.0037 3.1E-03 3.9E-02 -0.0037 3.5E-03 4.8E-02 -0.0042 9.5E-04 2.3E-02 -0.0037 3.2E-03 4.3E-02 -0.0036 3.3E-03 4.6E-02 eubacterium_biforme species -0.0031 1.1E-02 1.1E-01 -0.0037 2.3E-03 3.2E-02 -0.0036 3.6E-03 5.0E-02 -0.0037 3.1E-03 4.3E-02 -0.0037 3.5E-03 4.9E-02 -0.0042 9.5E-04 2.3E-02 -0.0037 3.2E-03 4.4E-02 -0.0036 3.3E-03 4.6E-02 clostridium_clostridioforme_unclassified strain 0.0011 7.9E-04 1.4E-02 0.0010 2.6E-03 3.6E-02 0.0010 2.6E-03 3.9E-02 0.0010 2.1E-03 3.2E-02 0.0009 8.8E-03 1.1E-01 0.0011 1.3E-03 2.3E-02 0.0010 1.6E-03 2.5E-02 0.0010 2.0E-03 3.1E-02 eggerthella genus 0.0019 1.2E-02 3.1E-01 0.0023 2.9E-03 8.4E-02 0.0022 4.8E-03 1.4E-01 0.0020 8.9E-03 2.6E-01 0.0020 7.4E-03 2.1E-01 0.0021 7.0E-03 2.0E-01 0.0020 7.6E-03 2.2E-01 0.0020 1.0E-02 2.9E-01 burkholderiales order 0.0035 7.0E-03 1.0E-01 0.0038 3.5E-03 5.3E-02 0.0037 5.2E-03 7.8E-02 0.0039 3.7E-03 5.5E-02 0.0039 3.5E-03 5.2E-02 0.0037 7.0E-03 1.0E-01 0.0038 4.0E-03 6.0E-02 0.0039 3.6E-03 5.4E-02 gcf_000166035 strain 0.0052 6.4E-03 7.9E-02 0.0056 4.0E-03 5.0E-02 0.0058 2.9E-03 3.9E-02 0.0057 3.1E-03 3.9E-02 0.0060 2.6E-03 4.0E-02 0.0053 7.5E-03 7.8E-02 0.0056 4.3E-03 5.2E-02 0.0056 4.1E-03 5.0E-02 betaproteobacteria class 0.0034 8.6E-03 1.0E-01 0.0037 4.5E-03 5.4E-02 0.0036 6.5E-03 7.8E-02 0.0038 4.7E-03 5.6E-02 0.0038 4.4E-03 5.3E-02 0.0036 8.6E-03 1.0E-01 0.0037 5.0E-03 6.0E-02 0.0038 4.5E-03 5.5E-02 sutterellaceae family 0.0031 1.3E-02 2.3E-01 0.0033 5.5E-03 1.6E-01 0.0034 6.9E-03 2.0E-01 0.0035 5.7E-03 1.7E-01 0.0035 5.8E-03 1.7E-01 0.0033 1.1E-02 3.1E-01 0.0034 6.0E-03 1.7E-01 0.0035 5.5E-03 1.6E-01 clostridium_hathewayi species 0.0013 9.3E-03 1.0E-01 0.0014 6.8E-03 8.1E-02 0.0014 4.8E-03 5.5E-02 0.0014 6.9E-03 8.0E-02 0.0014 5.5E-03 6.9E-02 0.0014 8.3E-03 8.3E-02 0.0014 5.6E-03 7.1E-02 0.0014 6.8E-03 7.8E-02 bacteroides_uniformis species -0.0099 9.1E-03 1.0E-01 -0.0105 7.0E-03 8.1E-02 -0.0112 4.0E-03 5.0E-02 -0.0107 5.6E-03 7.1E-02 -0.0102 9.1E-03 1.1E-01 -0.0115 3.6E-03 4.1E-02 -0.0104 7.3E-03 7.8E-02 -0.0105 6.7E-03 7.8E-02 gcf_000158075 strain 0.0011 5.3E-03 7.3E-02 0.0010 9.0E-03 1.0E-01 0.0011 7.1E-03 7.9E-02 0.0010 9.5E-03 1.1E-01 0.0009 2.8E-02 2.2E-01 0.0013 1.6E-03 2.3E-02 0.0011 7.1E-03 7.9E-02 0.0010 8.9E-03 1.0E-01 clostridium_asparagiforme species 0.0011 5.3E-03 7.4E-02 0.0010 9.0E-03 9.6E-02 0.0011 7.1E-03 7.6E-02 0.0010 9.5E-03 1.0E-01 0.0009 2.8E-02 2.3E-01 0.0013 1.6E-03 2.3E-02 0.0011 7.1E-03 7.8E-02 0.0010 8.9E-03 9.5E-02 gcf_000218405 strain 0.0016 1.1E-02 1.1E-01 0.0016 1.3E-02 1.3E-01 0.0017 8.4E-03 8.6E-02 0.0016 1.3E-02 1.4E-01 0.0016 1.4E-02 1.6E-01 0.0016 1.1E-02 9.9E-02 0.0016 1.1E-02 1.1E-01 0.0016 1.2E-02 1.2E-01 lachnospiraceae_bacterium_3_1_57faa_ct1 species 0.0016 1.1E-02 1.1E-01 0.0016 1.3E-02 1.3E-01 0.0017 8.4E-03 8.3E-02 0.0016 1.3E-02 1.3E-01 0.0016 1.4E-02 1.5E-01 0.0016 1.1E-02 9.8E-02 0.0016 1.1E-02 1.1E-01 0.0016 1.2E-02 1.2E-01 clostridium_hathewayi_unclassified strain 0.0011 2.3E-02 1.7E-01 0.0011 1.9E-02 1.8E-01 0.0011 1.5E-02 1.3E-01 0.0011 2.1E-02 1.9E-01 0.0011 1.7E-02 1.8E-01 0.0011 2.3E-02 1.7E-01 0.0011 1.6E-02 1.5E-01 0.0011 2.0E-02 1.9E-01 clostridium_symbiosum_unclassified strain 0.0013 9.6E-03 1.1E-01 0.0012 2.4E-02 2.1E-01 0.0012 2.0E-02 1.6E-01 0.0012 2.6E-02 2.0E-01 0.0012 2.8E-02 2.2E-01 0.0014 1.1E-02 9.9E-02 0.0011 3.2E-02 2.3E-01 0.0011 3.2E-02 2.3E-01 clostridium_symbiosum species 0.0013 9.6E-03 1.0E-01 0.0012 2.4E-02 2.2E-01 0.0012 2.0E-02 1.8E-01 0.0012 2.6E-02 2.2E-01 0.0012 2.8E-02 2.3E-01 0.0014 1.1E-02 9.8E-02 0.0011 3.2E-02 2.6E-01 0.0011 3.2E-02 2.6E-01 gcf_000172175 strain -0.0034 2.8E-02 2.1E-01 -0.0036 2.5E-02 2.1E-01 -0.0040 1.3E-02 1.3E-01 -0.0038 1.8E-02 1.7E-01 -0.0037 2.1E-02 2.0E-01 -0.0042 7.6E-03 7.8E-02 -0.0036 2.3E-02 2.0E-01 -0.0036 2.3E-02 2.0E-01 bacteroides_intestinalis species -0.0034 2.8E-02 2.3E-01 -0.0036 2.5E-02 2.2E-01 -0.0040 1.3E-02 1.2E-01 -0.0038 1.8E-02 1.6E-01 -0.0037 2.1E-02 2.1E-01 -0.0042 7.6E-03 8.1E-02 -0.0036 2.3E-02 2.1E-01 -0.0036 2.3E-02 2.2E-01 clostridiales_noname genus -0.0029 1.6E-02 3.1E-01 -0.0027 2.7E-02 3.2E-01 -0.0027 2.8E-02 2.7E-01 -0.0026 3.6E-02 3.0E-01 -0.0026 3.6E-02 3.0E-01 -0.0029 2.5E-02 3.3E-01 -0.0026 3.9E-02 3.2E-01 -0.0026 3.6E-02 3.2E-01 lactococcus_lactis_unclassified strain 0.0012 3.7E-02 2.4E-01 0.0013 2.7E-02 2.1E-01 0.0013 2.8E-02 1.9E-01 0.0013 3.2E-02 2.2E-01 0.0013 2.6E-02 2.2E-01 0.0013 3.2E-02 2.1E-01 0.0013 2.8E-02 2.3E-01 0.0013 2.6E-02 2.1E-01 lactococcus_lactis species 0.0012 3.7E-02 2.8E-01 0.0013 2.7E-02 2.2E-01 0.0013 2.8E-02 2.3E-01 0.0013 3.2E-02 2.5E-01 0.0013 2.6E-02 2.3E-01 0.0013 3.2E-02 2.3E-01 0.0013 2.8E-02 2.4E-01 0.0013 2.6E-02 2.2E-01 lactococcus genus 0.0012 4.0E-02 3.4E-01 0.0013 3.0E-02 3.2E-01 0.0013 3.1E-02 2.7E-01 0.0013 3.5E-02 3.0E-01 0.0013 2.8E-02 3.0E-01 0.0013 3.5E-02 3.3E-01 0.0013 3.0E-02 3.2E-01 0.0013 2.8E-02 3.2E-01 bacteroides_uniformis_unclassified strain -0.0091 2.0E-02 1.7E-01 -0.0087 3.0E-02 2.1E-01 -0.0095 1.8E-02 1.5E-01 -0.0090 2.4E-02 2.0E-01 -0.0083 4.0E-02 2.3E-01 -0.0097 1.7E-02 1.4E-01 -0.0087 3.0E-02 2.3E-01 -0.0087 2.8E-02 2.2E-01 dorea_formicigenerans_unclassified strain 0.0018 8.7E-02 4.0E-01 0.0023 3.1E-02 2.1E-01 0.0020 6.0E-02 2.7E-01 0.0020 5.7E-02 2.8E-01 0.0019 8.1E-02 3.8E-01 0.0017 1.1E-01 4.9E-01 0.0021 5.1E-02 2.5E-01 0.0021 4.8E-02 2.5E-01 dorea_formicigenerans species 0.0018 8.7E-02 4.0E-01 0.0023 3.1E-02 2.4E-01 0.0020 6.0E-02 2.9E-01 0.0020 5.7E-02 3.1E-01 0.0019 8.1E-02 3.9E-01 0.0017 1.1E-01 5.1E-01 0.0021 5.1E-02 2.8E-01 0.0021 4.8E-02 2.8E-01 bacteroides_vulgatus_unclassified strain -0.0055 3.9E-02 2.4E-01 -0.0059 3.2E-02 2.1E-01 -0.0061 2.6E-02 1.9E-01 -0.0058 3.4E-02 2.2E-01 -0.0060 3.2E-02 2.2E-01 -0.0042 1.2E-01 4.9E-01 -0.0055 4.2E-02 2.5E-01 -0.0056 3.9E-02 2.5E-01 clostridiaceae family 0.0059 3.6E-02 2.3E-01 0.0060 3.4E-02 3.5E-01 0.0060 3.7E-02 3.6E-01 0.0058 4.1E-02 3.7E-01 0.0053 6.6E-02 4.3E-01 0.0063 3.0E-02 4.1E-01 0.0059 4.0E-02 3.5E-01 0.0057 4.4E-02 2.9E-01 clostridium genus 0.0059 3.6E-02 3.4E-01 0.0060 3.5E-02 3.2E-01 0.0060 3.8E-02 2.7E-01 0.0058 4.1E-02 3.0E-01 0.0052 6.8E-02 4.4E-01 0.0063 3.0E-02 3.3E-01 0.0059 4.0E-02 3.2E-01 0.0057 4.4E-02 3.2E-01 gcf_000188175 strain 0.0005 6.9E-01 8.7E-01 0.0024 3.9E-02 2.4E-01 0.0024 3.7E-02 2.3E-01 0.0025 3.1E-02 2.2E-01 0.0025 3.2E-02 2.2E-01 0.0017 1.5E-01 5.5E-01 0.0024 3.8E-02 2.5E-01 0.0024 3.7E-02 2.5E-01 phascolarctobacterium_succinatutens species 0.0005 6.9E-01 8.9E-01 0.0024 3.9E-02 2.8E-01 0.0024 3.7E-02 2.6E-01 0.0025 3.1E-02 2.5E-01 0.0025 3.2E-02 2.5E-01 0.0017 1.5E-01 5.5E-01 0.0024 3.8E-02 2.8E-01 0.0024 3.7E-02 2.8E-01 phascolarctobacterium genus 0.0005 6.9E-01 8.7E-01 0.0024 3.9E-02 3.2E-01 0.0024 3.7E-02 2.7E-01 0.0025 3.1E-02 3.0E-01 0.0025 3.2E-02 3.0E-01 0.0017 1.5E-01 6.9E-01 0.0024 3.8E-02 3.2E-01 0.0024 3.7E-02 3.2E-01 anaerostipes genus 0.0020 3.6E-02 3.4E-01 0.0020 3.9E-02 3.2E-01 0.0022 2.6E-02 2.7E-01 0.0020 4.2E-02 3.0E-01 0.0021 3.5E-02 3.0E-01 0.0021 3.3E-02 3.3E-01 0.0021 3.5E-02 3.2E-01 0.0020 3.7E-02 3.2E-01 parabacteroides_goldsteinii_unclassified strain 0.0012 8.9E-02 4.0E-01 0.0014 4.1E-02 2.4E-01 0.0014 4.6E-02 2.6E-01 0.0014 4.2E-02 2.5E-01 0.0014 3.9E-02 2.3E-01 0.0016 3.0E-02 2.0E-01 0.0014 4.5E-02 2.5E-01 0.0014 4.8E-02 2.5E-01 parabacteroides_goldsteinii species 0.0012 8.9E-02 4.0E-01 0.0014 4.1E-02 2.8E-01 0.0014 4.6E-02 2.7E-01 0.0014 4.2E-02 3.0E-01 0.0014 3.9E-02 2.7E-01 0.0016 3.0E-02 2.3E-01 0.0014 4.5E-02 2.8E-01 0.0014 4.8E-02 2.8E-01 gcf_000154245 strain 0.0054 2.3E-02 1.7E-01 0.0048 4.7E-02 2.6E-01 0.0048 4.8E-02 2.6E-01 0.0048 4.7E-02 2.5E-01 NA NA NA 0.0049 4.5E-02 2.8E-01 0.0048 4.7E-02 2.5E-01 0.0048 4.4E-02 2.5E-01 clostridium_sp_l2_50 species 0.0054 2.3E-02 2.0E-01 0.0048 4.7E-02 2.8E-01 0.0048 4.8E-02 2.7E-01 0.0048 4.7E-02 3.0E-01 NA NA NA 0.0049 4.5E-02 3.1E-01 0.0048 4.7E-02 2.8E-01 0.0048 4.4E-02 2.8E-01 oscillibacter_unclassified species 0.0024 4.9E-02 2.8E-01 0.0024 4.7E-02 2.8E-01 0.0025 4.1E-02 2.7E-01 0.0023 5.8E-02 3.1E-01 0.0021 8.0E-02 3.9E-01 0.0018 1.5E-01 5.5E-01 0.0023 5.9E-02 3.2E-01 0.0022 6.4E-02 3.3E-01 bacteroides genus -0.0108 4.7E-02 3.4E-01 -0.0110 4.8E-02 3.5E-01 -0.0118 3.4E-02 2.7E-01 -0.0114 3.9E-02 3.0E-01 -0.0116 3.6E-02 3.0E-01 -0.0111 5.0E-02 4.1E-01 -0.0104 6.0E-02 3.8E-01 -0.0108 5.0E-02 3.2E-01 bacteroidaceae family -0.0108 4.7E-02 2.3E-01 -0.0110 4.8E-02 3.5E-01 -0.0118 3.4E-02 3.6E-01 -0.0114 3.9E-02 3.7E-01 -0.0116 3.6E-02 4.3E-01 -0.0111 5.0E-02 4.1E-01 -0.0104 6.0E-02 3.5E-01 -0.0108 5.0E-02 2.9E-01 bacteroides_vulgatus species -0.0053 4.4E-02 2.8E-01 -0.0053 4.9E-02 2.8E-01 -0.0056 3.8E-02 2.6E-01 -0.0052 5.1E-02 3.0E-01 -0.0054 5.1E-02 3.1E-01 -0.0041 1.3E-01 5.2E-01 -0.0050 6.3E-02 3.2E-01 -0.0051 5.8E-02 3.1E-01 gcf_000146185 strain -0.0056 5.1E-02 2.7E-01 -0.0057 4.9E-02 2.6E-01 -0.0051 8.2E-02 3.4E-01 -0.0051 8.1E-02 3.5E-01 -0.0049 9.5E-02 3.8E-01 -0.0049 9.7E-02 4.4E-01 -0.0051 8.2E-02 3.6E-01 -0.0052 7.6E-02 3.5E-01 eubacterium_eligens species -0.0056 5.1E-02 2.8E-01 -0.0057 4.9E-02 2.8E-01 -0.0051 8.2E-02 3.4E-01 -0.0051 8.1E-02 3.6E-01 -0.0049 9.5E-02 3.9E-01 -0.0049 9.7E-02 4.5E-01 -0.0051 8.2E-02 3.7E-01 -0.0052 7.6E-02 3.6E-01 gcf_000265365 strain 0.0021 4.0E-02 2.4E-01 0.0020 5.0E-02 2.6E-01 0.0021 4.7E-02 2.6E-01 0.0021 4.5E-02 2.5E-01 0.0022 3.7E-02 2.3E-01 0.0021 4.8E-02 2.8E-01 0.0021 4.2E-02 2.5E-01 0.0021 4.3E-02 2.5E-01 alistipes_finegoldii species 0.0021 4.0E-02 2.8E-01 0.0020 5.0E-02 2.8E-01 0.0021 4.7E-02 2.7E-01 0.0021 4.5E-02 3.0E-01 0.0022 3.7E-02 2.7E-01 0.0021 4.8E-02 3.2E-01 0.0021 4.2E-02 2.8E-01 0.0021 4.3E-02 2.8E-01 oxalobacter_formigenes species 0.0008 4.4E-02 2.8E-01 0.0008 5.7E-02 3.1E-01 0.0007 7.4E-02 3.3E-01 0.0007 6.5E-02 3.3E-01 0.0008 4.4E-02 2.9E-01 0.0006 1.2E-01 5.1E-01 0.0008 4.4E-02 2.8E-01 0.0008 4.8E-02 2.8E-01 oxalobacter genus 0.0008 4.4E-02 3.4E-01 0.0008 5.7E-02 3.7E-01 0.0007 7.4E-02 4.7E-01 0.0007 6.5E-02 4.2E-01 0.0008 4.4E-02 3.2E-01 0.0006 1.2E-01 6.9E-01 0.0008 4.4E-02 3.2E-01 0.0008 4.8E-02 3.2E-01 oxalobacteraceae family 0.0008 4.7E-02 2.3E-01 0.0007 6.0E-02 3.5E-01 0.0007 7.7E-02 3.7E-01 0.0007 6.7E-02 3.7E-01 0.0008 4.6E-02 4.3E-01 0.0006 1.2E-01 6.0E-01 0.0008 4.6E-02 3.5E-01 0.0008 5.0E-02 2.9E-01 veillonellaceae family -0.0055 4.6E-02 2.3E-01 -0.0053 6.1E-02 3.5E-01 -0.0053 6.2E-02 3.6E-01 -0.0054 5.5E-02 3.7E-01 -0.0051 7.6E-02 4.3E-01 -0.0050 8.5E-02 4.9E-01 -0.0055 5.1E-02 3.5E-01 -0.0055 4.9E-02 2.9E-01 15

Supplementary Data 1b MV + renal function MV + pre-DM and MV & Exclude DM MV + FFQ MV + DDR (5d avg) MV + DDR (2d avg) Taxonom Basic Model MV + HBA1c Taxonomic label indicator DM status patients phosphorus intake phosphorus intake phosphorus intake ic type Effect P FDR Effect P FDR Effect P FDR Effect P FDR Effect P FDR Effect P FDR Effect P FDR Effect P FDR gcf_000218385 strain 0.0008 1.2E-01 4.3E-01 0.0010 6.2E-02 3.0E-01 0.0012 3.0E-02 1.9E-01 0.0011 4.7E-02 2.5E-01 0.0011 4.7E-02 2.6E-01 0.0010 6.0E-02 3.2E-01 0.0011 4.6E-02 2.5E-01 0.0011 4.4E-02 2.5E-01 lachnospiraceae_bacterium_1_4_56faa species 0.0008 1.2E-01 4.3E-01 0.0010 6.2E-02 3.2E-01 0.0012 3.0E-02 2.3E-01 0.0011 4.7E-02 3.0E-01 0.0011 4.7E-02 3.0E-01 0.0010 6.0E-02 3.7E-01 0.0011 4.6E-02 2.8E-01 0.0011 4.4E-02 2.8E-01 bacteroides_dorei_unclassified strain -0.0050 4.5E-02 2.7E-01 -0.0048 6.4E-02 3.0E-01 -0.0048 6.0E-02 2.7E-01 -0.0047 6.6E-02 3.1E-01 -0.0048 6.5E-02 3.3E-01 -0.0041 1.2E-01 4.9E-01 -0.0045 7.8E-02 3.6E-01 -0.0046 7.0E-02 3.3E-01 gcf_000242155 strain 0.0008 1.2E-01 4.2E-01 0.0009 6.9E-02 3.2E-01 0.0009 8.0E-02 3.4E-01 0.0008 1.1E-01 4.4E-01 0.0008 9.4E-02 3.8E-01 0.0009 7.3E-02 3.8E-01 0.0008 9.3E-02 3.8E-01 0.0008 1.0E-01 4.0E-01 lachnospiraceae_bacterium_7_1_58faa species 0.0008 1.2E-01 4.3E-01 0.0009 6.9E-02 3.4E-01 0.0009 8.0E-02 3.4E-01 0.0008 1.1E-01 4.3E-01 0.0008 9.4E-02 3.9E-01 0.0009 7.3E-02 4.2E-01 0.0008 9.3E-02 3.9E-01 0.0008 1.0E-01 4.2E-01 bacteroides_dorei species -0.0049 5.0E-02 2.8E-01 -0.0046 7.1E-02 3.4E-01 -0.0047 6.6E-02 3.1E-01 -0.0046 7.3E-02 3.5E-01 -0.0047 7.2E-02 3.9E-01 -0.0039 1.3E-01 5.3E-01 -0.0044 8.6E-02 3.7E-01 -0.0045 7.8E-02 3.6E-01 gcf_000239295 strain 0.0008 9.4E-02 4.0E-01 0.0008 7.7E-02 3.4E-01 0.0008 8.9E-02 3.5E-01 0.0007 1.2E-01 4.4E-01 0.0008 9.3E-02 3.8E-01 0.0007 1.4E-01 5.4E-01 0.0008 1.0E-01 4.0E-01 0.0007 1.1E-01 4.1E-01 flavonifractor_plautii species 0.0008 9.4E-02 4.0E-01 0.0008 7.7E-02 3.6E-01 0.0008 8.9E-02 3.5E-01 0.0007 1.2E-01 4.4E-01 0.0008 9.3E-02 3.9E-01 0.0007 1.4E-01 5.4E-01 0.0008 1.0E-01 4.1E-01 0.0007 1.1E-01 4.3E-01 flavonifractor genus 0.0008 9.4E-02 4.9E-01 0.0008 7.7E-02 4.5E-01 0.0008 8.9E-02 4.7E-01 0.0007 1.2E-01 5.5E-01 0.0008 9.3E-02 5.4E-01 0.0007 1.4E-01 6.9E-01 0.0008 1.0E-01 5.3E-01 0.0007 1.1E-01 5.3E-01 clostridiales_noname family -0.0026 4.8E-02 2.3E-01 -0.0023 7.9E-02 3.8E-01 -0.0025 6.3E-02 3.6E-01 -0.0023 7.7E-02 3.7E-01 -0.0023 8.9E-02 4.3E-01 -0.0026 5.7E-02 4.1E-01 -0.0023 7.9E-02 3.8E-01 -0.0023 7.4E-02 3.6E-01 clostridium_bolteae species 0.0024 6.9E-02 3.7E-01 0.0023 8.8E-02 3.9E-01 0.0025 6.1E-02 2.9E-01 0.0023 8.6E-02 3.7E-01 0.0022 1.0E-01 4.1E-01 0.0024 8.0E-02 4.2E-01 0.0023 8.2E-02 3.7E-01 0.0022 9.5E-02 4.1E-01 gcf_000144975 strain -0.0009 1.0E-01 4.0E-01 -0.0009 8.9E-02 3.8E-01 -0.0009 8.2E-02 3.4E-01 -0.0009 1.0E-01 4.2E-01 -0.0008 1.3E-01 4.4E-01 -0.0008 1.6E-01 5.5E-01 -0.0009 1.0E-01 4.0E-01 -0.0009 1.0E-01 4.0E-01 burkholderiales_bacterium_1_1_47 species -0.0009 1.0E-01 4.0E-01 -0.0009 8.9E-02 3.9E-01 -0.0009 8.2E-02 3.4E-01 -0.0009 1.0E-01 4.2E-01 -0.0008 1.3E-01 4.5E-01 -0.0008 1.6E-01 5.6E-01 -0.0009 1.0E-01 4.1E-01 -0.0009 1.0E-01 4.2E-01 burkholderiales_noname genus -0.0009 1.0E-01 4.9E-01 -0.0009 8.9E-02 4.7E-01 -0.0009 8.2E-02 4.7E-01 -0.0009 1.0E-01 5.5E-01 -0.0008 1.3E-01 5.4E-01 -0.0008 1.6E-01 6.9E-01 -0.0009 1.0E-01 5.3E-01 -0.0009 1.0E-01 5.3E-01 dorea genus 0.0027 1.2E-01 4.9E-01 0.0029 9.7E-02 4.7E-01 0.0024 1.7E-01 5.4E-01 0.0024 1.7E-01 5.5E-01 0.0024 1.7E-01 5.9E-01 0.0021 2.3E-01 7.2E-01 0.0025 1.5E-01 5.3E-01 0.0025 1.5E-01 5.3E-01 burkholderiales_noname family -0.0008 1.3E-01 4.3E-01 -0.0008 1.2E-01 4.4E-01 -0.0009 1.1E-01 4.1E-01 -0.0008 1.3E-01 5.2E-01 -0.0007 1.6E-01 5.5E-01 -0.0007 2.1E-01 6.0E-01 -0.0008 1.3E-01 5.3E-01 -0.0008 1.3E-01 5.3E-01 gcf_000024265 strain 0.0006 5.1E-02 2.7E-01 0.0005 1.2E-01 4.8E-01 0.0006 5.1E-02 2.6E-01 0.0005 7.8E-02 3.5E-01 0.0005 6.9E-02 3.4E-01 0.0005 8.1E-02 4.0E-01 0.0005 8.1E-02 3.6E-01 0.0005 8.4E-02 3.7E-01 eggerthella_lenta species 0.0006 5.1E-02 2.8E-01 0.0005 1.2E-01 5.0E-01 0.0006 5.1E-02 2.7E-01 0.0005 7.8E-02 3.6E-01 0.0005 6.9E-02 3.9E-01 0.0005 8.1E-02 4.2E-01 0.0005 8.1E-02 3.7E-01 0.0005 8.4E-02 3.8E-01 oscillibacter genus 0.0016 1.5E-01 5.7E-01 0.0018 1.2E-01 5.0E-01 0.0018 1.3E-01 5.3E-01 0.0016 1.6E-01 5.5E-01 0.0014 2.4E-01 6.6E-01 0.0012 2.9E-01 7.4E-01 0.0016 1.6E-01 5.3E-01 0.0016 1.6E-01 5.3E-01 oscillospiraceae family 0.0016 1.5E-01 4.3E-01 0.0018 1.2E-01 4.4E-01 0.0018 1.3E-01 4.1E-01 0.0016 1.6E-01 5.2E-01 0.0014 2.4E-01 5.5E-01 0.0012 2.9E-01 6.2E-01 0.0016 1.6E-01 5.3E-01 0.0016 1.6E-01 5.3E-01 subdoligranulum genus 0.0038 1.9E-01 5.7E-01 0.0046 1.2E-01 5.0E-01 0.0045 1.4E-01 5.3E-01 0.0046 1.3E-01 5.5E-01 0.0046 1.3E-01 5.4E-01 0.0041 1.9E-01 7.2E-01 0.0046 1.2E-01 5.3E-01 0.0045 1.3E-01 5.3E-01 gcf_000154445 strain 0.0006 1.9E-01 5.4E-01 0.0007 1.2E-01 4.8E-01 0.0008 9.8E-02 3.6E-01 0.0007 1.2E-01 4.5E-01 0.0007 1.1E-01 4.2E-01 0.0007 1.6E-01 5.5E-01 0.0006 1.9E-01 5.1E-01 0.0006 1.7E-01 4.9E-01 clostridium_bartlettii species 0.0006 1.9E-01 5.8E-01 0.0007 1.2E-01 5.0E-01 0.0008 9.8E-02 3.7E-01 0.0007 1.2E-01 4.5E-01 0.0007 1.1E-01 4.2E-01 0.0007 1.6E-01 5.6E-01 0.0006 1.9E-01 5.4E-01 0.0006 1.7E-01 5.2E-01 gcf_000231275 strain 0.0014 1.0E-01 4.0E-01 0.0013 1.3E-01 4.8E-01 0.0012 1.8E-01 4.9E-01 0.0013 1.3E-01 4.5E-01 0.0013 1.1E-01 4.2E-01 0.0011 2.2E-01 6.0E-01 0.0014 1.1E-01 4.0E-01 0.0014 1.1E-01 4.1E-01 alistipes_indistinctus species 0.0014 1.0E-01 4.0E-01 0.0013 1.3E-01 5.0E-01 0.0012 1.8E-01 5.2E-01 0.0013 1.3E-01 4.5E-01 0.0013 1.1E-01 4.2E-01 0.0011 2.2E-01 6.3E-01 0.0014 1.1E-01 4.2E-01 0.0014 1.1E-01 4.3E-01 subdoligranulum_unclassified species 0.0037 2.0E-01 5.9E-01 0.0044 1.3E-01 5.0E-01 0.0043 1.5E-01 4.7E-01 0.0045 1.4E-01 4.7E-01 0.0044 1.4E-01 4.7E-01 0.0039 2.0E-01 5.9E-01 0.0045 1.3E-01 4.7E-01 0.0044 1.4E-01 4.9E-01 bacteroides_cellulosilyticus species 0.0037 1.2E-01 4.3E-01 0.0037 1.3E-01 5.0E-01 0.0039 1.1E-01 4.1E-01 0.0038 1.3E-01 4.5E-01 0.0038 1.3E-01 4.5E-01 0.0027 2.5E-01 6.4E-01 0.0037 1.3E-01 4.7E-01 0.0037 1.3E-01 4.9E-01 veillonella_unclassified species -0.0018 7.3E-02 3.8E-01 -0.0015 1.4E-01 5.0E-01 -0.0020 5.3E-02 2.7E-01 -0.0019 7.0E-02 3.5E-01 -0.0017 9.3E-02 3.9E-01 -0.0019 7.6E-02 4.2E-01 -0.0019 6.8E-02 3.4E-01 -0.0018 7.4E-02 3.6E-01 ruminococcus_torques_unclassified strain 0.0030 1.5E-01 5.0E-01 0.0031 1.4E-01 4.8E-01 0.0031 1.5E-01 4.4E-01 0.0032 1.4E-01 4.7E-01 0.0027 2.1E-01 5.1E-01 0.0029 1.8E-01 5.5E-01 0.0036 9.1E-02 3.8E-01 0.0035 1.0E-01 4.0E-01 gcf_000374505 strain -0.0029 2.5E-01 5.5E-01 -0.0038 1.4E-01 4.8E-01 -0.0031 2.4E-01 5.4E-01 -0.0034 1.9E-01 5.1E-01 -0.0032 2.2E-01 5.1E-01 -0.0030 2.5E-01 6.1E-01 -0.0036 1.6E-01 4.8E-01 -0.0036 1.6E-01 4.9E-01 alistipes_onderdonkii species -0.0029 2.5E-01 5.9E-01 -0.0038 1.4E-01 5.0E-01 -0.0031 2.4E-01 5.8E-01 -0.0034 1.9E-01 5.5E-01 -0.0032 2.2E-01 5.4E-01 -0.0030 2.5E-01 6.4E-01 -0.0036 1.6E-01 5.1E-01 -0.0036 1.6E-01 5.1E-01 bacteroides_cellulosilyticus_unclassified strain 0.0036 1.3E-01 4.5E-01 0.0036 1.4E-01 4.8E-01 0.0038 1.2E-01 4.1E-01 0.0037 1.4E-01 4.7E-01 0.0037 1.4E-01 4.7E-01 0.0026 2.7E-01 6.2E-01 0.0036 1.4E-01 4.6E-01 0.0036 1.4E-01 4.8E-01 gcf_000154365 strain 0.0021 1.2E-01 4.3E-01 0.0021 1.5E-01 4.8E-01 0.0023 1.1E-01 3.9E-01 0.0021 1.5E-01 4.8E-01 0.0020 1.7E-01 5.0E-01 0.0019 1.8E-01 5.5E-01 0.0021 1.4E-01 4.6E-01 0.0020 1.6E-01 4.9E-01 bifidobacterium_longum species -0.0029 2.1E-01 5.9E-01 -0.0034 1.5E-01 5.0E-01 -0.0038 1.1E-01 4.0E-01 -0.0035 1.4E-01 4.8E-01 -0.0033 1.8E-01 5.2E-01 -0.0038 1.2E-01 5.1E-01 -0.0036 1.3E-01 4.7E-01 -0.0035 1.4E-01 4.9E-01 gcf_000154065 strain 0.0027 1.1E-01 4.1E-01 0.0024 1.5E-01 4.8E-01 0.0022 1.9E-01 5.1E-01 0.0023 1.7E-01 5.0E-01 0.0024 1.6E-01 4.9E-01 0.0022 2.0E-01 5.6E-01 0.0024 1.5E-01 4.7E-01 0.0024 1.6E-01 4.9E-01 dorea_longicatena species 0.0027 1.1E-01 4.1E-01 0.0024 1.5E-01 5.0E-01 0.0022 1.9E-01 5.4E-01 0.0023 1.7E-01 5.3E-01 0.0024 1.6E-01 4.9E-01 0.0022 2.0E-01 5.9E-01 0.0024 1.5E-01 5.0E-01 0.0024 1.6E-01 5.0E-01 bifidobacterium_longum_unclassified strain -0.0029 2.2E-01 5.5E-01 -0.0034 1.5E-01 4.8E-01 -0.0038 1.1E-01 3.9E-01 -0.0035 1.4E-01 4.8E-01 -0.0032 1.8E-01 5.0E-01 -0.0037 1.2E-01 4.9E-01 -0.0035 1.4E-01 4.6E-01 -0.0035 1.4E-01 4.8E-01 gcf_000478885 strain 0.0015 9.9E-02 4.0E-01 0.0013 1.5E-01 4.8E-01 0.0014 1.4E-01 4.2E-01 0.0013 1.6E-01 4.9E-01 0.0014 1.3E-01 4.4E-01 0.0008 3.6E-01 6.9E-01 0.0014 1.4E-01 4.6E-01 0.0013 1.5E-01 4.8E-01 adlercreutzia_equolifaciens species 0.0015 9.9E-02 4.0E-01 0.0013 1.5E-01 5.0E-01 0.0014 1.4E-01 4.4E-01 0.0013 1.6E-01 5.2E-01 0.0014 1.3E-01 4.5E-01 0.0008 3.6E-01 7.2E-01 0.0014 1.4E-01 4.8E-01 0.0013 1.5E-01 4.9E-01 adlercreutzia genus 0.0015 9.9E-02 4.9E-01 0.0013 1.5E-01 5.6E-01 0.0014 1.4E-01 5.3E-01 0.0013 1.6E-01 5.5E-01 0.0014 1.3E-01 5.4E-01 0.0008 3.6E-01 8.1E-01 0.0014 1.4E-01 5.3E-01 0.0013 1.5E-01 5.3E-01 erysipelotrichaceae_noname genus -0.0015 2.6E-01 6.4E-01 -0.0019 1.6E-01 5.6E-01 -0.0019 1.8E-01 5.4E-01 -0.0020 1.6E-01 5.5E-01 -0.0020 1.6E-01 5.8E-01 -0.0020 1.7E-01 6.9E-01 -0.0020 1.5E-01 5.3E-01 -0.0020 1.5E-01 5.3E-01 dialister genus -0.0034 1.8E-01 5.7E-01 -0.0036 1.6E-01 5.6E-01 -0.0033 2.0E-01 5.8E-01 -0.0034 1.9E-01 5.8E-01 -0.0032 2.3E-01 6.6E-01 -0.0029 2.8E-01 7.4E-01 -0.0034 1.9E-01 5.4E-01 -0.0035 1.7E-01 5.3E-01 gcf_000195615 strain 0.0007 2.5E-01 5.5E-01 0.0009 1.6E-01 5.0E-01 0.0010 9.1E-02 3.5E-01 0.0009 1.5E-01 4.8E-01 0.0009 1.4E-01 4.7E-01 0.0008 1.8E-01 5.5E-01 0.0009 1.4E-01 4.6E-01 0.0009 1.5E-01 4.9E-01 bacteroides_clarus species 0.0007 2.5E-01 5.9E-01 0.0009 1.6E-01 5.3E-01 0.0010 9.1E-02 3.5E-01 0.0009 1.5E-01 5.0E-01 0.0009 1.4E-01 4.7E-01 0.0008 1.8E-01 5.9E-01 0.0009 1.4E-01 4.7E-01 0.0009 1.5E-01 5.0E-01 ruminococcus_lactaris species 0.0019 2.7E-01 6.0E-01 0.0025 1.7E-01 5.3E-01 0.0026 1.6E-01 4.7E-01 0.0029 1.1E-01 4.4E-01 0.0030 9.4E-02 3.9E-01 0.0035 5.8E-02 3.7E-01 0.0028 1.3E-01 4.7E-01 0.0027 1.3E-01 4.9E-01 ruminococcus_lactaris_unclassified strain 0.0019 2.7E-01 5.5E-01 0.0025 1.7E-01 5.0E-01 0.0026 1.6E-01 4.5E-01 0.0028 1.1E-01 4.4E-01 0.0030 9.5E-02 3.8E-01 0.0035 5.9E-02 3.2E-01 0.0027 1.3E-01 4.6E-01 0.0027 1.3E-01 4.8E-01 gcf_000209875 strain 0.0065 8.4E-02 4.0E-01 0.0052 1.7E-01 5.0E-01 0.0047 2.3E-01 5.4E-01 0.0050 1.9E-01 5.1E-01 0.0051 1.9E-01 5.0E-01 0.0086 2.3E-02 1.7E-01 0.0049 2.0E-01 5.1E-01 0.0047 2.2E-01 5.2E-01 ruminococcus_bromii species 0.0065 8.4E-02 4.0E-01 0.0052 1.7E-01 5.3E-01 0.0047 2.3E-01 5.8E-01 0.0050 1.9E-01 5.5E-01 0.0051 1.9E-01 5.2E-01 0.0086 2.3E-02 1.9E-01 0.0049 2.0E-01 5.4E-01 0.0047 2.2E-01 5.5E-01 klebsiella genus 0.0023 1.1E-01 4.9E-01 0.0021 1.7E-01 5.6E-01 0.0021 1.7E-01 5.4E-01 0.0021 1.7E-01 5.5E-01 0.0012 4.5E-01 8.5E-01 0.0012 4.4E-01 8.1E-01 0.0021 1.7E-01 5.4E-01 0.0021 1.7E-01 5.3E-01 veillonella_atypica_unclassified strain 0.0004 4.5E-01 7.4E-01 0.0007 1.8E-01 5.0E-01 0.0004 4.9E-01 7.7E-01 0.0004 4.5E-01 7.6E-01 0.0005 3.7E-01 6.9E-01 0.0005 3.6E-01 6.9E-01 0.0004 4.7E-01 7.7E-01 0.0004 4.5E-01 7.7E-01 veillonella_atypica species 0.0004 4.5E-01 7.2E-01 0.0007 1.8E-01 5.3E-01 0.0004 4.9E-01 8.2E-01 0.0004 4.5E-01 7.8E-01 0.0005 3.7E-01 7.0E-01 0.0005 3.6E-01 7.2E-01 0.0004 4.7E-01 7.9E-01 0.0004 4.5E-01 7.9E-01 acidaminococcaceae family 0.0003 8.5E-01 9.1E-01 0.0020 1.8E-01 5.7E-01 0.0019 1.9E-01 5.6E-01 0.0021 1.5E-01 5.2E-01 0.0017 2.5E-01 5.5E-01 0.0013 3.8E-01 6.9E-01 0.0020 1.7E-01 5.3E-01 0.0020 1.7E-01 5.3E-01 viruses_noname class -0.0021 3.0E-01 7.7E-01 -0.0026 1.9E-01 8.1E-01 -0.0024 2.4E-01 7.7E-01 -0.0025 2.1E-01 7.8E-01 -0.0025 2.3E-01 8.1E-01 -0.0026 2.1E-01 8.1E-01 -0.0026 2.0E-01 7.9E-01 -0.0026 2.0E-01 8.0E-01 viruses_noname phylum -0.0021 3.0E-01 8.5E-01 -0.0026 1.9E-01 8.2E-01 -0.0024 2.4E-01 7.7E-01 -0.0025 2.1E-01 7.8E-01 -0.0025 2.3E-01 8.0E-01 -0.0026 2.1E-01 7.9E-01 -0.0026 2.0E-01 7.0E-01 -0.0026 2.0E-01 7.8E-01 viruses kingdom -0.0021 3.0E-01 4.7E-01 -0.0026 1.9E-01 3.8E-01 -0.0024 2.4E-01 4.0E-01 -0.0025 2.1E-01 3.6E-01 -0.0025 2.3E-01 4.4E-01 -0.0026 2.1E-01 3.8E-01 -0.0026 2.0E-01 3.4E-01 -0.0026 2.0E-01 3.5E-01 eubacterium_sp_3_1_31_unclassified strain -0.0006 2.4E-01 5.5E-01 -0.0006 1.9E-01 5.2E-01 -0.0006 2.1E-01 5.1E-01 -0.0007 1.6E-01 4.9E-01 -0.0007 1.8E-01 5.0E-01 -0.0003 4.9E-01 7.4E-01 -0.0007 1.9E-01 5.1E-01 -0.0007 1.8E-01 5.2E-01 eubacterium_sp_3_1_31 species -0.0006 2.4E-01 5.9E-01 -0.0006 1.9E-01 5.6E-01 -0.0006 2.1E-01 5.4E-01 -0.0007 1.6E-01 5.2E-01 -0.0007 1.8E-01 5.2E-01 -0.0003 4.9E-01 7.8E-01 -0.0007 1.9E-01 5.4E-01 -0.0007 1.8E-01 5.5E-01 prevotellaceae family 0.0066 1.3E-01 4.3E-01 0.0057 2.0E-01 5.7E-01 0.0068 1.2E-01 4.1E-01 0.0059 1.8E-01 5.3E-01 0.0066 1.4E-01 5.5E-01 0.0021 6.3E-01 8.2E-01 0.0054 2.2E-01 5.8E-01 0.0056 2.0E-01 5.3E-01 gcf_000242175 strain 0.0003 2.9E-01 5.7E-01 0.0004 2.0E-01 5.2E-01 0.0003 2.9E-01 6.0E-01 0.0004 2.8E-01 5.7E-01 0.0004 2.6E-01 5.4E-01 0.0004 2.5E-01 6.1E-01 0.0004 2.1E-01 5.1E-01 0.0004 2.0E-01 5.2E-01 erysipelotrichaceae_bacterium_6_1_45 species 0.0003 2.9E-01 6.1E-01 0.0004 2.0E-01 5.6E-01 0.0003 2.9E-01 6.4E-01 0.0004 2.8E-01 6.0E-01 0.0004 2.6E-01 5.8E-01 0.0004 2.5E-01 6.4E-01 0.0004 2.1E-01 5.4E-01 0.0004 2.0E-01 5.5E-01 gcf_000153885 strain 0.0016 1.2E-01 4.2E-01 0.0013 2.0E-01 5.2E-01 0.0013 2.0E-01 5.1E-01 0.0013 2.0E-01 5.1E-01 0.0013 2.0E-01 5.0E-01 0.0015 1.7E-01 5.5E-01 0.0013 2.0E-01 5.1E-01 0.0013 2.0E-01 5.2E-01 eubacterium_ventriosum species 0.0016 1.2E-01 4.3E-01 0.0013 2.0E-01 5.6E-01 0.0013 2.0E-01 5.4E-01 0.0013 2.0E-01 5.5E-01 0.0013 2.0E-01 5.2E-01 0.0015 1.7E-01 5.6E-01 0.0013 2.0E-01 5.4E-01 0.0013 2.0E-01 5.5E-01 streptococcus_vestibularis_unclassified strain -0.0006 2.1E-01 5.5E-01 -0.0007 2.1E-01 5.2E-01 -0.0008 1.2E-01 4.1E-01 -0.0007 1.8E-01 5.1E-01 -0.0008 1.5E-01 4.8E-01 -0.0007 2.0E-01 5.6E-01 -0.0007 1.9E-01 5.1E-01 -0.0007 2.0E-01 5.2E-01 streptococcus_vestibularis species -0.0006 2.1E-01 5.9E-01 -0.0007 2.1E-01 5.6E-01 -0.0008 1.2E-01 4.2E-01 -0.0007 1.8E-01 5.4E-01 -0.0008 1.5E-01 4.8E-01 -0.0007 2.0E-01 5.9E-01 -0.0007 1.9E-01 5.4E-01 -0.0007 2.0E-01 5.5E-01 gcf_000160055 strain -0.0031 2.2E-01 5.5E-01 -0.0033 2.1E-01 5.2E-01 -0.0030 2.4E-01 5.4E-01 -0.0030 2.3E-01 5.6E-01 -0.0028 2.8E-01 5.6E-01 -0.0025 3.4E-01 6.9E-01 -0.0031 2.3E-01 5.3E-01 -0.0032 2.2E-01 5.2E-01 dialister_invisus species -0.0031 2.2E-01 5.9E-01 -0.0033 2.1E-01 5.6E-01 -0.0030 2.4E-01 5.8E-01 -0.0030 2.3E-01 5.9E-01 -0.0028 2.8E-01 5.9E-01 -0.0025 3.4E-01 7.2E-01 -0.0031 2.3E-01 5.5E-01 -0.0032 2.2E-01 5.5E-01 gcf_000218465 strain 0.0007 1.6E-01 5.1E-01 0.0007 2.1E-01 5.2E-01 0.0008 1.4E-01 4.2E-01 0.0007 2.1E-01 5.1E-01 0.0007 1.9E-01 5.0E-01 0.0006 2.6E-01 6.1E-01 0.0007 2.1E-01 5.1E-01 0.0007 2.1E-01 5.2E-01 lachnospiraceae_bacterium_2_1_58faa species 0.0007 1.6E-01 5.5E-01 0.0007 2.1E-01 5.6E-01 0.0008 1.4E-01 4.4E-01 0.0007 2.1E-01 5.5E-01 0.0007 1.9E-01 5.2E-01 0.0006 2.6E-01 6.4E-01 0.0007 2.1E-01 5.4E-01 0.0007 2.1E-01 5.5E-01 gcf_000187895 strain -0.0012 3.2E-01 6.1E-01 -0.0016 2.1E-01 5.2E-01 -0.0017 1.7E-01 4.8E-01 -0.0016 2.0E-01 5.1E-01 -0.0016 2.1E-01 5.1E-01 -0.0016 2.3E-01 6.1E-01 -0.0016 2.1E-01 5.1E-01 -0.0016 2.1E-01 5.2E-01 16

Supplementary Data 1b MV + renal function MV + pre-DM and MV & Exclude DM MV + FFQ MV + DDR (5d avg) MV + DDR (2d avg) Taxonom Basic Model MV + HBA1c Taxonomic label indicator DM status patients phosphorus intake phosphorus intake phosphorus intake ic type Effect P FDR Effect P FDR Effect P FDR Effect P FDR Effect P FDR Effect P FDR Effect P FDR Effect P FDR bacteroides_plebeius species -0.0012 3.2E-01 6.5E-01 -0.0016 2.1E-01 5.6E-01 -0.0017 1.7E-01 5.0E-01 -0.0016 2.0E-01 5.5E-01 -0.0016 2.1E-01 5.4E-01 -0.0016 2.3E-01 6.4E-01 -0.0016 2.1E-01 5.4E-01 -0.0016 2.1E-01 5.5E-01 prevotella genus 0.0058 1.7E-01 5.7E-01 0.0053 2.3E-01 7.0E-01 0.0066 1.3E-01 5.3E-01 0.0055 2.1E-01 6.0E-01 0.0063 1.5E-01 5.8E-01 0.0019 6.7E-01 9.0E-01 0.0050 2.6E-01 6.8E-01 0.0052 2.4E-01 6.6E-01 proteobacteria phylum 0.0035 2.0E-01 8.5E-01 0.0032 2.3E-01 8.2E-01 0.0037 1.9E-01 7.7E-01 0.0034 2.2E-01 7.8E-01 0.0037 2.0E-01 8.0E-01 0.0026 3.6E-01 7.9E-01 0.0036 2.0E-01 7.0E-01 0.0034 2.2E-01 7.8E-01 gcf_000332875 strain 0.0009 2.6E-01 5.5E-01 0.0010 2.4E-01 5.7E-01 0.0010 2.4E-01 5.4E-01 0.0009 2.6E-01 5.7E-01 0.0010 2.3E-01 5.2E-01 0.0010 2.3E-01 6.1E-01 0.0010 2.2E-01 5.2E-01 0.0010 2.2E-01 5.2E-01 anaerostipes_hadrus species 0.0009 2.6E-01 6.0E-01 0.0010 2.4E-01 6.1E-01 0.0010 2.4E-01 5.8E-01 0.0009 2.6E-01 6.0E-01 0.0010 2.3E-01 5.6E-01 0.0010 2.3E-01 6.4E-01 0.0010 2.2E-01 5.5E-01 0.0010 2.2E-01 5.5E-01 lachnospiraceae family 0.0028 4.5E-01 6.8E-01 0.0045 2.4E-01 6.1E-01 0.0043 2.6E-01 6.2E-01 0.0039 3.0E-01 6.1E-01 0.0040 3.0E-01 5.5E-01 0.0054 1.7E-01 6.0E-01 0.0043 2.6E-01 6.0E-01 0.0043 2.6E-01 6.2E-01 bifidobacterium_adolescentis_unclassified strain 0.0031 2.4E-01 5.5E-01 0.0032 2.4E-01 5.7E-01 0.0031 2.4E-01 5.4E-01 0.0034 2.0E-01 5.1E-01 0.0040 1.5E-01 4.7E-01 0.0036 1.8E-01 5.5E-01 0.0034 2.1E-01 5.1E-01 0.0034 2.0E-01 5.2E-01 bifidobacterium_adolescentis species 0.0031 2.4E-01 5.9E-01 0.0032 2.4E-01 6.1E-01 0.0031 2.4E-01 5.8E-01 0.0034 2.0E-01 5.5E-01 0.0040 1.5E-01 4.7E-01 0.0036 1.8E-01 5.9E-01 0.0034 2.1E-01 5.4E-01 0.0034 2.0E-01 5.5E-01 gcf_000312145 strain 0.0006 2.6E-01 5.5E-01 0.0006 2.4E-01 5.7E-01 0.0005 3.0E-01 6.0E-01 0.0006 2.3E-01 5.5E-01 0.0007 1.7E-01 5.0E-01 0.0005 4.0E-01 7.4E-01 0.0006 2.3E-01 5.2E-01 0.0006 2.2E-01 5.2E-01 alistipes_senegalensis species 0.0006 2.6E-01 6.0E-01 0.0006 2.4E-01 6.1E-01 0.0005 3.0E-01 6.4E-01 0.0006 2.3E-01 5.9E-01 0.0007 1.7E-01 5.1E-01 0.0005 4.0E-01 7.7E-01 0.0006 2.3E-01 5.5E-01 0.0006 2.2E-01 5.5E-01 roseburia genus 0.0027 3.4E-01 6.5E-01 0.0033 2.5E-01 7.0E-01 0.0027 3.5E-01 7.4E-01 0.0027 3.4E-01 7.6E-01 0.0026 3.8E-01 8.1E-01 0.0033 2.5E-01 7.2E-01 0.0028 3.2E-01 7.0E-01 0.0027 3.3E-01 7.3E-01 alistipes genus 0.0055 1.2E-01 4.9E-01 0.0042 2.5E-01 7.0E-01 0.0040 2.8E-01 7.0E-01 0.0044 2.3E-01 6.3E-01 0.0049 1.9E-01 6.0E-01 0.0051 1.6E-01 6.9E-01 0.0048 1.8E-01 5.4E-01 0.0047 1.9E-01 5.6E-01 rikenellaceae family 0.0055 1.2E-01 4.3E-01 0.0042 2.5E-01 6.1E-01 0.0040 2.8E-01 6.2E-01 0.0044 2.3E-01 6.0E-01 0.0049 1.9E-01 5.5E-01 0.0051 1.6E-01 6.0E-01 0.0048 1.8E-01 5.3E-01 0.0047 1.9E-01 5.3E-01 bacteria kingdom 0.0025 3.1E-01 4.7E-01 0.0029 2.5E-01 3.8E-01 0.0028 2.9E-01 4.0E-01 0.0027 2.9E-01 3.6E-01 0.0027 3.0E-01 4.4E-01 0.0021 4.3E-01 4.3E-01 0.0027 2.9E-01 3.4E-01 0.0027 2.9E-01 3.5E-01 gcf_000205165 strain 0.0004 2.4E-01 5.5E-01 0.0004 2.6E-01 5.8E-01 0.0004 2.5E-01 5.4E-01 0.0004 2.5E-01 5.7E-01 0.0005 2.4E-01 5.2E-01 0.0003 4.7E-01 7.4E-01 0.0005 2.3E-01 5.3E-01 0.0005 2.3E-01 5.3E-01 paraprevotella_xylaniphila species 0.0004 2.4E-01 5.9E-01 0.0004 2.6E-01 6.2E-01 0.0004 2.5E-01 5.8E-01 0.0004 2.5E-01 6.0E-01 0.0005 2.4E-01 5.6E-01 0.0003 4.7E-01 7.8E-01 0.0005 2.3E-01 5.5E-01 0.0005 2.3E-01 5.6E-01 gcf_000226135 strain 0.0012 1.9E-01 5.4E-01 0.0010 2.8E-01 6.0E-01 0.0012 2.0E-01 5.1E-01 0.0010 2.6E-01 5.7E-01 0.0016 9.4E-02 3.8E-01 0.0013 2.0E-01 5.6E-01 0.0010 2.8E-01 5.9E-01 0.0010 2.7E-01 5.8E-01 bacteroides_faecis species 0.0012 1.9E-01 5.8E-01 0.0010 2.8E-01 6.4E-01 0.0012 2.0E-01 5.4E-01 0.0010 2.6E-01 6.0E-01 0.0016 9.4E-02 3.9E-01 0.0013 2.0E-01 5.9E-01 0.0010 2.8E-01 6.1E-01 0.0010 2.7E-01 6.0E-01 gcf_000157935 strain 0.0054 2.0E-01 5.5E-01 0.0047 2.8E-01 6.0E-01 0.0061 1.5E-01 4.5E-01 0.0050 2.5E-01 5.7E-01 0.0058 1.8E-01 5.0E-01 0.0014 7.5E-01 8.7E-01 0.0044 3.1E-01 6.2E-01 0.0046 2.9E-01 5.9E-01 prevotella_copri species 0.0054 2.0E-01 5.9E-01 0.0047 2.8E-01 6.4E-01 0.0061 1.5E-01 4.7E-01 0.0050 2.5E-01 6.0E-01 0.0058 1.8E-01 5.2E-01 0.0014 7.5E-01 8.9E-01 0.0044 3.1E-01 6.5E-01 0.0046 2.9E-01 6.1E-01 gcf_000173435 strain 0.0013 1.9E-01 5.4E-01 0.0011 2.9E-01 6.0E-01 0.0011 2.5E-01 5.4E-01 0.0010 2.9E-01 5.9E-01 0.0011 2.8E-01 5.6E-01 0.0010 3.2E-01 6.8E-01 0.0009 3.5E-01 6.7E-01 0.0010 3.2E-01 6.3E-01 bifidobacterium_pseudocatenulatum species 0.0013 1.9E-01 5.8E-01 0.0011 2.9E-01 6.4E-01 0.0011 2.5E-01 5.8E-01 0.0010 2.9E-01 6.3E-01 0.0011 2.8E-01 5.9E-01 0.0010 3.2E-01 7.2E-01 0.0009 3.5E-01 6.8E-01 0.0010 3.2E-01 6.6E-01 gcf_000468015 strain -0.0015 2.8E-01 5.5E-01 -0.0015 2.9E-01 6.0E-01 -0.0022 1.3E-01 4.2E-01 -0.0019 1.8E-01 5.1E-01 -0.0018 2.1E-01 5.1E-01 -0.0012 4.0E-01 7.4E-01 -0.0017 2.5E-01 5.3E-01 -0.0017 2.5E-01 5.5E-01 ruminococcus_callidus species -0.0015 2.8E-01 6.0E-01 -0.0015 2.9E-01 6.4E-01 -0.0022 1.3E-01 4.4E-01 -0.0019 1.8E-01 5.4E-01 -0.0018 2.1E-01 5.4E-01 -0.0012 4.0E-01 7.7E-01 -0.0017 2.5E-01 5.6E-01 -0.0017 2.5E-01 5.8E-01 gcf_000218445 strain -0.0016 3.5E-01 6.4E-01 -0.0019 2.9E-01 6.0E-01 -0.0019 3.0E-01 6.0E-01 -0.0019 2.8E-01 5.7E-01 -0.0021 2.4E-01 5.2E-01 -0.0019 3.0E-01 6.5E-01 -0.0019 2.8E-01 5.9E-01 -0.0019 2.9E-01 5.9E-01 lachnospiraceae_bacterium_1_1_57faa species -0.0016 3.5E-01 6.6E-01 -0.0019 2.9E-01 6.4E-01 -0.0019 3.0E-01 6.4E-01 -0.0019 2.8E-01 6.0E-01 -0.0021 2.4E-01 5.6E-01 -0.0019 3.0E-01 7.0E-01 -0.0019 2.8E-01 6.1E-01 -0.0019 2.9E-01 6.1E-01 gcf_000169255 strain 0.0004 2.3E-01 5.5E-01 0.0003 2.9E-01 6.0E-01 0.0003 3.0E-01 6.0E-01 0.0003 3.1E-01 6.0E-01 0.0004 2.6E-01 5.5E-01 0.0002 5.0E-01 7.4E-01 0.0003 3.3E-01 6.6E-01 0.0003 3.4E-01 6.6E-01 pseudoflavonifractor_capillosus species 0.0004 2.3E-01 5.9E-01 0.0003 2.9E-01 6.4E-01 0.0003 3.0E-01 6.4E-01 0.0003 3.1E-01 6.5E-01 0.0004 2.6E-01 5.9E-01 0.0002 5.0E-01 7.8E-01 0.0003 3.3E-01 6.7E-01 0.0003 3.4E-01 6.8E-01 pseudoflavonifractor genus 0.0004 2.3E-01 6.4E-01 0.0003 2.9E-01 7.0E-01 0.0003 3.0E-01 7.2E-01 0.0003 3.1E-01 7.4E-01 0.0004 2.6E-01 7.0E-01 0.0002 5.0E-01 8.1E-01 0.0003 3.3E-01 7.0E-01 0.0003 3.4E-01 7.3E-01 lactobacillus genus -0.0013 1.9E-01 5.7E-01 -0.0011 2.9E-01 7.0E-01 -0.0015 1.5E-01 5.3E-01 -0.0015 1.4E-01 5.5E-01 -0.0016 1.2E-01 5.4E-01 -0.0018 8.3E-02 6.0E-01 -0.0015 1.5E-01 5.3E-01 -0.0014 1.6E-01 5.3E-01 ruminococcus_torques species 0.0019 3.4E-01 6.5E-01 0.0021 2.9E-01 6.4E-01 0.0023 2.7E-01 6.1E-01 0.0023 2.6E-01 6.0E-01 0.0019 3.5E-01 6.9E-01 0.0020 3.4E-01 7.2E-01 0.0027 1.9E-01 5.4E-01 0.0026 2.1E-01 5.5E-01 gcf_000154205 strain -0.0011 5.6E-01 8.1E-01 -0.0020 3.0E-01 6.0E-01 -0.0020 3.1E-01 6.2E-01 -0.0020 3.0E-01 5.9E-01 NA NA NA -0.0021 3.0E-01 6.5E-01 -0.0020 2.9E-01 5.9E-01 -0.0020 3.0E-01 6.0E-01 eubacterium genus -0.0058 2.7E-01 6.4E-01 -0.0056 3.0E-01 7.0E-01 -0.0054 3.2E-01 7.4E-01 -0.0050 3.5E-01 7.6E-01 -0.0058 2.9E-01 7.3E-01 -0.0040 4.7E-01 8.1E-01 -0.0050 3.5E-01 7.0E-01 -0.0049 3.7E-01 7.3E-01 eubacteriaceae family -0.0058 2.7E-01 6.8E-01 -0.0056 3.0E-01 6.3E-01 -0.0054 3.2E-01 6.3E-01 -0.0050 3.5E-01 6.1E-01 -0.0058 2.9E-01 5.5E-01 -0.0040 4.7E-01 7.2E-01 -0.0050 3.5E-01 6.0E-01 -0.0049 3.7E-01 6.4E-01 holdemania genus 0.0005 2.9E-01 6.4E-01 0.0005 3.1E-01 7.0E-01 0.0004 3.6E-01 7.4E-01 0.0004 4.4E-01 7.7E-01 0.0002 6.1E-01 8.8E-01 0.0003 5.6E-01 8.3E-01 0.0005 2.7E-01 6.9E-01 0.0005 3.1E-01 7.3E-01 desulfovibrio genus 0.0006 3.5E-01 6.6E-01 0.0006 3.2E-01 7.0E-01 0.0007 2.5E-01 6.6E-01 0.0007 2.8E-01 7.1E-01 0.0008 2.2E-01 6.6E-01 0.0002 7.2E-01 9.3E-01 0.0007 2.9E-01 6.9E-01 0.0007 2.9E-01 7.3E-01 odoribacter_unclassified species 0.0006 4.4E-01 7.1E-01 0.0007 3.2E-01 6.8E-01 0.0005 5.2E-01 8.3E-01 0.0006 3.7E-01 7.4E-01 0.0007 2.7E-01 5.9E-01 0.0007 3.2E-01 7.2E-01 0.0008 2.4E-01 5.5E-01 0.0008 2.6E-01 5.9E-01 gcf_000185705 strain 0.0005 1.7E-01 5.1E-01 0.0004 3.3E-01 6.5E-01 0.0005 2.0E-01 5.1E-01 0.0005 2.6E-01 5.7E-01 0.0005 2.4E-01 5.2E-01 0.0004 3.5E-01 6.9E-01 0.0005 1.8E-01 5.1E-01 0.0005 2.5E-01 5.5E-01 bilophila_wadsworthia species 0.0005 1.7E-01 5.5E-01 0.0004 3.3E-01 6.9E-01 0.0005 2.0E-01 5.4E-01 0.0005 2.6E-01 6.0E-01 0.0005 2.4E-01 5.6E-01 0.0004 3.5E-01 7.2E-01 0.0005 1.8E-01 5.4E-01 0.0005 2.5E-01 5.8E-01 erysipelotrichaceae family -0.0010 5.4E-01 6.9E-01 -0.0015 3.4E-01 6.3E-01 -0.0014 3.9E-01 6.3E-01 -0.0016 3.1E-01 6.1E-01 -0.0017 3.0E-01 5.5E-01 -0.0017 2.8E-01 6.2E-01 -0.0016 3.1E-01 6.0E-01 -0.0016 3.1E-01 6.4E-01 erysipelotrichales order -0.0010 5.4E-01 9.0E-01 -0.0015 3.4E-01 7.7E-01 -0.0014 3.9E-01 7.0E-01 -0.0016 3.1E-01 7.5E-01 -0.0017 3.0E-01 7.7E-01 -0.0017 2.8E-01 8.9E-01 -0.0016 3.1E-01 7.5E-01 -0.0016 3.1E-01 7.5E-01 erysipelotrichia class -0.0010 5.4E-01 7.7E-01 -0.0015 3.4E-01 8.1E-01 -0.0014 3.9E-01 7.7E-01 -0.0016 3.1E-01 7.8E-01 -0.0017 3.0E-01 8.1E-01 -0.0017 2.8E-01 8.1E-01 -0.0016 3.1E-01 7.9E-01 -0.0016 3.1E-01 8.0E-01 sutterella_wadsworthensis species 0.0009 4.2E-01 7.1E-01 0.0011 3.4E-01 6.9E-01 0.0009 4.2E-01 7.9E-01 0.0011 3.4E-01 6.9E-01 0.0010 4.2E-01 7.6E-01 0.0012 3.1E-01 7.2E-01 0.0012 3.3E-01 6.6E-01 0.0012 3.2E-01 6.6E-01 bifidobacterium_bifidum_unclassified strain -0.0019 9.0E-02 4.0E-01 -0.0010 3.4E-01 6.7E-01 -0.0023 5.2E-02 2.6E-01 -0.0023 5.2E-02 2.7E-01 -0.0022 6.3E-02 3.3E-01 -0.0020 9.1E-02 4.3E-01 -0.0023 4.8E-02 2.5E-01 -0.0023 5.0E-02 2.5E-01 bifidobacterium_bifidum species -0.0019 9.0E-02 4.0E-01 -0.0010 3.4E-01 6.9E-01 -0.0023 5.2E-02 2.7E-01 -0.0023 5.2E-02 3.0E-01 -0.0022 6.3E-02 3.6E-01 -0.0020 9.1E-02 4.4E-01 -0.0023 4.8E-02 2.8E-01 -0.0023 5.0E-02 2.8E-01 desulfovibrio_desulfuricans species 0.0004 3.8E-01 6.8E-01 0.0005 3.4E-01 6.9E-01 0.0005 3.3E-01 6.8E-01 0.0005 3.4E-01 6.9E-01 0.0005 3.2E-01 6.6E-01 0.0004 4.5E-01 7.8E-01 0.0005 2.7E-01 6.1E-01 0.0005 3.1E-01 6.4E-01 gcf_000154465 strain 0.0032 2.4E-01 5.5E-01 0.0026 3.5E-01 6.8E-01 0.0027 3.4E-01 6.6E-01 0.0030 2.7E-01 5.7E-01 0.0033 2.4E-01 5.2E-01 0.0030 2.9E-01 6.4E-01 0.0032 2.4E-01 5.3E-01 0.0032 2.5E-01 5.5E-01 alistipes_putredinis species 0.0032 2.4E-01 5.9E-01 0.0026 3.5E-01 7.0E-01 0.0027 3.4E-01 6.9E-01 0.0030 2.7E-01 6.0E-01 0.0033 2.4E-01 5.6E-01 0.0030 2.9E-01 6.9E-01 0.0032 2.4E-01 5.5E-01 0.0032 2.5E-01 5.8E-01 lactobacillales order 0.0027 3.0E-01 9.0E-01 0.0025 3.6E-01 7.7E-01 0.0018 5.1E-01 7.0E-01 0.0020 4.6E-01 7.5E-01 0.0017 5.3E-01 7.7E-01 0.0014 6.0E-01 8.9E-01 0.0018 5.1E-01 7.5E-01 0.0020 4.6E-01 7.5E-01 eubacterium_rectale_unclassified strain -0.0052 3.4E-01 6.3E-01 -0.0051 3.6E-01 6.9E-01 -0.0051 3.7E-01 6.8E-01 -0.0040 4.8E-01 7.7E-01 -0.0056 3.2E-01 6.3E-01 -0.0033 5.6E-01 8.0E-01 -0.0049 3.8E-01 7.0E-01 -0.0046 4.1E-01 7.7E-01 eubacterium_rectale species -0.0052 3.4E-01 6.5E-01 -0.0051 3.6E-01 7.1E-01 -0.0051 3.7E-01 7.1E-01 -0.0040 4.8E-01 8.0E-01 -0.0056 3.2E-01 6.6E-01 -0.0033 5.6E-01 8.4E-01 -0.0049 3.8E-01 7.0E-01 -0.0046 4.1E-01 7.7E-01 selenomonadales order -0.0042 1.3E-01 9.0E-01 -0.0026 3.7E-01 7.7E-01 -0.0027 3.4E-01 7.0E-01 -0.0026 3.6E-01 7.5E-01 -0.0028 3.2E-01 7.7E-01 -0.0025 3.9E-01 8.9E-01 -0.0027 3.4E-01 7.5E-01 -0.0027 3.3E-01 7.5E-01 negativicutes class -0.0042 1.3E-01 7.7E-01 -0.0026 3.7E-01 8.1E-01 -0.0027 3.4E-01 7.7E-01 -0.0026 3.6E-01 7.8E-01 -0.0028 3.2E-01 8.1E-01 -0.0025 3.9E-01 8.1E-01 -0.0027 3.4E-01 7.9E-01 -0.0027 3.3E-01 8.0E-01 ruminococcaceae family 0.0037 3.5E-01 6.8E-01 0.0036 3.7E-01 6.3E-01 0.0032 4.4E-01 6.3E-01 0.0032 4.4E-01 6.3E-01 0.0037 3.8E-01 6.1E-01 0.0042 3.2E-01 6.2E-01 0.0030 4.6E-01 6.6E-01 0.0031 4.5E-01 6.5E-01 bacilli class 0.0027 3.1E-01 7.7E-01 0.0024 3.7E-01 8.1E-01 0.0017 5.2E-01 7.7E-01 0.0019 4.7E-01 7.8E-01 0.0017 5.4E-01 8.1E-01 0.0014 6.2E-01 9.1E-01 0.0017 5.3E-01 7.9E-01 0.0019 4.8E-01 8.0E-01 parabacteroides_johnsonii species 0.0009 3.4E-01 6.5E-01 0.0009 3.7E-01 7.2E-01 0.0010 3.1E-01 6.6E-01 0.0008 3.8E-01 7.5E-01 0.0008 4.1E-01 7.5E-01 0.0017 8.6E-02 4.2E-01 0.0009 3.8E-01 7.0E-01 0.0009 3.8E-01 7.2E-01 sutterella genus 0.0009 4.6E-01 7.6E-01 0.0010 3.7E-01 7.9E-01 0.0009 4.5E-01 7.9E-01 0.0011 3.7E-01 7.6E-01 0.0009 4.5E-01 8.5E-01 0.0011 3.5E-01 8.1E-01 0.0011 3.6E-01 7.0E-01 0.0011 3.6E-01 7.3E-01 methanobrevibacter genus 0.0013 4.3E-01 7.3E-01 0.0015 3.8E-01 7.9E-01 0.0015 3.8E-01 7.4E-01 0.0016 3.4E-01 7.6E-01 0.0014 4.1E-01 8.5E-01 0.0021 2.4E-01 7.2E-01 0.0017 3.2E-01 7.0E-01 0.0017 3.3E-01 7.3E-01 peptostreptococcaceae_noname_unclassified species -0.0009 3.4E-01 6.5E-01 -0.0009 3.9E-01 7.3E-01 -0.0007 4.6E-01 8.0E-01 -0.0007 4.5E-01 7.8E-01 -0.0007 4.6E-01 8.0E-01 -0.0009 3.9E-01 7.7E-01 -0.0010 3.2E-01 6.6E-01 -0.0009 3.5E-01 7.0E-01 parabacteroides_distasonis_unclassified strain -0.0010 5.5E-01 8.0E-01 -0.0015 3.9E-01 7.2E-01 -0.0008 6.4E-01 8.7E-01 -0.0011 5.2E-01 7.9E-01 -0.0010 5.8E-01 8.5E-01 -0.0014 4.3E-01 7.4E-01 -0.0012 4.9E-01 7.7E-01 -0.0012 5.0E-01 7.7E-01 parabacteroides_distasonis species -0.0010 5.5E-01 8.1E-01 -0.0015 3.9E-01 7.3E-01 -0.0008 6.4E-01 8.9E-01 -0.0011 5.2E-01 8.2E-01 -0.0010 5.8E-01 8.7E-01 -0.0014 4.3E-01 7.8E-01 -0.0012 4.9E-01 8.0E-01 -0.0012 5.0E-01 8.0E-01 siphoviridae family -0.0010 5.6E-01 6.9E-01 -0.0015 3.9E-01 6.3E-01 -0.0014 4.5E-01 6.3E-01 -0.0015 4.2E-01 6.3E-01 -0.0014 4.5E-01 6.5E-01 -0.0015 4.2E-01 7.2E-01 -0.0015 4.0E-01 6.4E-01 -0.0015 4.0E-01 6.4E-01 gcf_000311925 strain 0.0015 3.1E-01 6.0E-01 0.0013 4.0E-01 7.3E-01 0.0011 4.6E-01 7.6E-01 0.0013 3.9E-01 7.3E-01 0.0014 3.7E-01 6.9E-01 0.0011 4.7E-01 7.4E-01 0.0014 3.4E-01 6.6E-01 0.0013 3.8E-01 7.2E-01 bacteroidales_bacterium_ph8 species 0.0015 3.1E-01 6.4E-01 0.0013 4.0E-01 7.4E-01 0.0011 4.6E-01 8.0E-01 0.0013 3.9E-01 7.5E-01 0.0014 3.7E-01 7.0E-01 0.0011 4.7E-01 7.8E-01 0.0014 3.4E-01 6.7E-01 0.0013 3.8E-01 7.2E-01 bacteroidales_noname genus 0.0015 3.1E-01 6.5E-01 0.0013 4.0E-01 8.0E-01 0.0011 4.6E-01 7.9E-01 0.0013 3.9E-01 7.6E-01 0.0014 3.7E-01 8.1E-01 0.0011 4.7E-01 8.1E-01 0.0014 3.4E-01 7.0E-01 0.0013 3.8E-01 7.3E-01 bacteroidales_noname family 0.0015 3.1E-01 6.8E-01 0.0013 4.0E-01 6.3E-01 0.0011 4.6E-01 6.3E-01 0.0013 3.9E-01 6.2E-01 0.0014 3.7E-01 6.1E-01 0.0011 4.7E-01 7.2E-01 0.0014 3.4E-01 6.0E-01 0.0013 3.8E-01 6.4E-01 euryarchaeota phylum 0.0012 4.7E-01 8.5E-01 0.0014 4.1E-01 8.5E-01 0.0014 4.0E-01 7.7E-01 0.0016 3.6E-01 7.8E-01 0.0013 4.4E-01 8.8E-01 0.0020 2.5E-01 7.9E-01 0.0016 3.4E-01 7.9E-01 0.0016 3.5E-01 8.0E-01 archaea kingdom 0.0012 4.7E-01 4.7E-01 0.0014 4.1E-01 4.1E-01 0.0014 4.0E-01 4.0E-01 0.0016 3.6E-01 3.6E-01 0.0013 4.4E-01 4.4E-01 0.0020 2.5E-01 3.8E-01 0.0016 3.4E-01 3.4E-01 0.0016 3.5E-01 3.5E-01 methanobacteriaceae family 0.0012 4.7E-01 6.8E-01 0.0014 4.1E-01 6.3E-01 0.0014 4.0E-01 6.3E-01 0.0016 3.6E-01 6.1E-01 0.0013 4.4E-01 6.5E-01 0.0020 2.5E-01 6.2E-01 0.0016 3.4E-01 6.0E-01 0.0016 3.5E-01 6.4E-01 17

Supplementary Data 1b MV + renal function MV + pre-DM and MV & Exclude DM MV + FFQ MV + DDR (5d avg) MV + DDR (2d avg) Taxonom Basic Model MV + HBA1c Taxonomic label indicator DM status patients phosphorus intake phosphorus intake phosphorus intake ic type Effect P FDR Effect P FDR Effect P FDR Effect P FDR Effect P FDR Effect P FDR Effect P FDR Effect P FDR methanobacteriales order 0.0012 4.7E-01 9.0E-01 0.0014 4.1E-01 7.7E-01 0.0014 4.0E-01 7.0E-01 0.0016 3.6E-01 7.5E-01 0.0013 4.4E-01 7.7E-01 0.0020 2.5E-01 8.9E-01 0.0016 3.4E-01 7.5E-01 0.0016 3.5E-01 7.5E-01 methanobacteria class 0.0012 4.7E-01 7.7E-01 0.0014 4.1E-01 8.1E-01 0.0014 4.0E-01 7.7E-01 0.0016 3.6E-01 7.8E-01 0.0013 4.4E-01 8.1E-01 0.0020 2.5E-01 8.1E-01 0.0016 3.4E-01 7.9E-01 0.0016 3.5E-01 8.0E-01 methanobrevibacter_smithii_unclassified strain 0.0011 4.6E-01 7.4E-01 0.0013 4.2E-01 7.5E-01 0.0013 4.1E-01 7.4E-01 0.0014 3.7E-01 7.2E-01 0.0015 3.4E-01 6.5E-01 0.0018 2.6E-01 6.1E-01 0.0015 3.4E-01 6.6E-01 0.0014 3.6E-01 6.8E-01 methanobrevibacter_smithii species 0.0011 4.6E-01 7.3E-01 0.0013 4.2E-01 7.6E-01 0.0013 4.1E-01 7.8E-01 0.0014 3.7E-01 7.4E-01 0.0015 3.4E-01 6.9E-01 0.0018 2.6E-01 6.4E-01 0.0015 3.4E-01 6.7E-01 0.0014 3.6E-01 7.0E-01 gcf_000155875 strain 0.0004 7.4E-01 8.8E-01 0.0010 4.2E-01 7.5E-01 0.0007 5.8E-01 8.4E-01 0.0009 4.9E-01 7.7E-01 0.0009 5.0E-01 8.3E-01 0.0012 3.5E-01 6.9E-01 0.0009 4.8E-01 7.7E-01 0.0009 4.7E-01 7.7E-01 coprococcus_comes species 0.0004 7.4E-01 8.9E-01 0.0010 4.2E-01 7.6E-01 0.0007 5.8E-01 8.7E-01 0.0009 4.9E-01 8.0E-01 0.0009 5.0E-01 8.4E-01 0.0012 3.5E-01 7.2E-01 0.0009 4.8E-01 7.9E-01 0.0009 4.7E-01 8.0E-01 propionibacteriaceae family -0.0003 5.7E-01 6.9E-01 -0.0004 4.3E-01 6.3E-01 -0.0005 3.3E-01 6.3E-01 -0.0005 3.3E-01 6.1E-01 -0.0006 3.1E-01 5.5E-01 -0.0006 3.1E-01 6.2E-01 -0.0004 4.2E-01 6.4E-01 -0.0004 4.3E-01 6.5E-01 lactobacillaceae family -0.0010 3.3E-01 6.8E-01 -0.0008 4.3E-01 6.3E-01 -0.0011 2.7E-01 6.2E-01 -0.0011 2.7E-01 6.1E-01 -0.0012 2.4E-01 5.5E-01 -0.0014 1.9E-01 6.0E-01 -0.0011 2.9E-01 6.0E-01 -0.0011 3.0E-01 6.4E-01 bacteroides_ovatus_unclassified strain -0.0014 5.3E-01 7.8E-01 -0.0017 4.4E-01 7.6E-01 -0.0017 4.6E-01 7.6E-01 -0.0018 4.2E-01 7.6E-01 -0.0019 4.0E-01 7.2E-01 -0.0017 4.5E-01 7.4E-01 -0.0018 4.2E-01 7.4E-01 -0.0017 4.4E-01 7.7E-01 gcf_000157995 strain 0.0004 3.3E-01 6.2E-01 0.0003 4.4E-01 7.6E-01 0.0004 4.2E-01 7.4E-01 0.0003 5.4E-01 7.9E-01 0.0002 6.9E-01 8.5E-01 0.0002 6.5E-01 8.1E-01 0.0004 3.7E-01 6.9E-01 0.0003 4.2E-01 7.7E-01 holdemania_filiformis species 0.0004 3.3E-01 6.5E-01 0.0003 4.4E-01 7.8E-01 0.0004 4.2E-01 7.8E-01 0.0003 5.4E-01 8.4E-01 0.0002 6.9E-01 9.0E-01 0.0002 6.5E-01 8.6E-01 0.0004 3.7E-01 7.0E-01 0.0003 4.2E-01 7.8E-01 butyrivibrio genus 0.0026 2.7E-01 6.4E-01 0.0018 4.4E-01 8.3E-01 0.0023 3.4E-01 7.4E-01 0.0020 4.0E-01 7.6E-01 0.0023 3.4E-01 7.8E-01 0.0027 2.6E-01 7.2E-01 0.0018 4.6E-01 7.7E-01 0.0018 4.4E-01 7.9E-01 gcf_000210595 strain -0.0036 1.9E-01 5.4E-01 -0.0021 4.5E-01 7.6E-01 -0.0019 5.0E-01 7.7E-01 -0.0021 4.5E-01 7.6E-01 -0.0017 5.5E-01 8.5E-01 -0.0014 6.4E-01 8.0E-01 -0.0024 3.8E-01 7.0E-01 -0.0022 4.4E-01 7.7E-01 coprococcus_sp_art55_1 species -0.0036 1.9E-01 5.8E-01 -0.0021 4.5E-01 7.9E-01 -0.0019 5.0E-01 8.2E-01 -0.0021 4.5E-01 7.8E-01 -0.0017 5.5E-01 8.5E-01 -0.0014 6.4E-01 8.5E-01 -0.0024 3.8E-01 7.0E-01 -0.0022 4.4E-01 7.9E-01 gcf_000156015 strain 0.0026 2.7E-01 5.5E-01 0.0018 4.5E-01 7.6E-01 0.0022 3.5E-01 6.6E-01 0.0019 4.1E-01 7.6E-01 0.0023 3.5E-01 6.5E-01 0.0026 2.7E-01 6.2E-01 0.0017 4.7E-01 7.7E-01 0.0018 4.5E-01 7.7E-01 butyrivibrio_crossotus species 0.0026 2.7E-01 6.0E-01 0.0018 4.5E-01 7.9E-01 0.0022 3.5E-01 7.0E-01 0.0019 4.1E-01 7.8E-01 0.0023 3.5E-01 6.9E-01 0.0026 2.7E-01 6.6E-01 0.0017 4.7E-01 7.9E-01 0.0018 4.5E-01 7.9E-01 streptococcus_salivarius_unclassified strain 0.0016 3.7E-01 6.6E-01 0.0014 4.6E-01 7.7E-01 0.0011 5.6E-01 8.2E-01 0.0014 4.6E-01 7.6E-01 0.0013 4.9E-01 8.3E-01 0.0013 5.0E-01 7.4E-01 0.0011 5.4E-01 7.9E-01 0.0013 4.9E-01 7.7E-01 streptococcus_salivarius species 0.0016 3.7E-01 6.8E-01 0.0014 4.6E-01 7.9E-01 0.0011 5.6E-01 8.6E-01 0.0014 4.6E-01 7.8E-01 0.0013 4.9E-01 8.3E-01 0.0013 5.0E-01 7.8E-01 0.0011 5.4E-01 8.2E-01 0.0013 4.9E-01 8.0E-01 bacteroides_finegoldii species 0.0006 5.6E-01 8.1E-01 0.0008 4.8E-01 8.1E-01 0.0010 3.6E-01 7.1E-01 0.0008 4.5E-01 7.8E-01 0.0010 3.7E-01 7.0E-01 0.0006 6.0E-01 8.4E-01 0.0008 4.6E-01 7.9E-01 0.0008 4.7E-01 8.0E-01 gcf_000173795 strain -0.0003 6.1E-01 8.3E-01 -0.0005 4.8E-01 7.7E-01 -0.0005 4.6E-01 7.6E-01 -0.0005 4.4E-01 7.6E-01 -0.0005 4.7E-01 8.0E-01 -0.0008 2.4E-01 6.1E-01 -0.0005 4.8E-01 7.7E-01 -0.0005 4.8E-01 7.7E-01 catenibacterium_mitsuokai species -0.0003 6.1E-01 8.6E-01 -0.0005 4.8E-01 8.1E-01 -0.0005 4.6E-01 8.0E-01 -0.0005 4.4E-01 7.8E-01 -0.0005 4.7E-01 8.0E-01 -0.0008 2.4E-01 6.4E-01 -0.0005 4.8E-01 7.9E-01 -0.0005 4.8E-01 8.0E-01 catenibacterium genus -0.0003 6.1E-01 8.2E-01 -0.0005 4.8E-01 8.3E-01 -0.0005 4.6E-01 7.9E-01 -0.0005 4.4E-01 7.7E-01 -0.0005 4.7E-01 8.5E-01 -0.0008 2.4E-01 7.2E-01 -0.0005 4.8E-01 7.7E-01 -0.0005 4.8E-01 8.0E-01 veillonella genus -0.0013 2.7E-01 6.4E-01 -0.0009 4.9E-01 8.3E-01 -0.0016 2.1E-01 5.8E-01 -0.0014 2.5E-01 6.5E-01 -0.0013 3.1E-01 7.5E-01 -0.0016 2.2E-01 7.2E-01 -0.0015 2.4E-01 6.6E-01 -0.0014 2.6E-01 6.8E-01 gcf_000159975 strain -0.0015 6.7E-01 8.7E-01 -0.0024 4.9E-01 7.7E-01 -0.0011 7.6E-01 8.7E-01 -0.0020 5.7E-01 8.0E-01 -0.0012 7.3E-01 8.9E-01 -0.0025 4.8E-01 7.4E-01 -0.0029 4.0E-01 7.2E-01 -0.0024 4.9E-01 7.7E-01 ruminococcus_sp_5_1_39bfaa species -0.0015 6.7E-01 8.9E-01 -0.0024 4.9E-01 8.1E-01 -0.0011 7.6E-01 8.9E-01 -0.0020 5.7E-01 8.5E-01 -0.0012 7.3E-01 9.1E-01 -0.0025 4.8E-01 7.8E-01 -0.0029 4.0E-01 7.2E-01 -0.0024 4.9E-01 8.0E-01 veillonella_parvula_unclassified strain 0.0002 7.2E-01 8.8E-01 0.0004 5.0E-01 7.7E-01 0.0001 8.9E-01 9.3E-01 0.0001 8.6E-01 9.2E-01 0.0002 7.5E-01 9.0E-01 -0.0001 8.6E-01 9.3E-01 0.0001 8.8E-01 9.4E-01 0.0001 8.6E-01 9.1E-01 veillonella_parvula species 0.0002 7.2E-01 8.9E-01 0.0004 5.0E-01 8.1E-01 0.0001 8.9E-01 9.6E-01 0.0001 8.6E-01 9.4E-01 0.0002 7.5E-01 9.1E-01 -0.0001 8.6E-01 9.4E-01 0.0001 8.8E-01 9.5E-01 0.0001 8.6E-01 9.4E-01 gcf_000020225 strain 0.0024 5.3E-01 7.8E-01 0.0025 5.1E-01 7.7E-01 0.0029 4.4E-01 7.6E-01 0.0028 4.6E-01 7.6E-01 0.0025 5.2E-01 8.3E-01 0.0009 8.1E-01 9.0E-01 0.0025 5.1E-01 7.9E-01 0.0025 5.1E-01 7.7E-01 akkermansia_muciniphila species 0.0024 5.3E-01 8.0E-01 0.0025 5.1E-01 8.1E-01 0.0029 4.4E-01 8.0E-01 0.0028 4.6E-01 7.8E-01 0.0025 5.2E-01 8.4E-01 0.0009 8.1E-01 9.1E-01 0.0025 5.1E-01 8.2E-01 0.0025 5.1E-01 8.0E-01 akkermansia genus 0.0024 5.3E-01 7.9E-01 0.0025 5.1E-01 8.3E-01 0.0029 4.4E-01 7.9E-01 0.0028 4.6E-01 7.9E-01 0.0025 5.2E-01 8.5E-01 0.0009 8.1E-01 9.4E-01 0.0025 5.1E-01 7.7E-01 0.0025 5.1E-01 8.0E-01 verrucomicrobiaceae family 0.0024 5.3E-01 6.9E-01 0.0025 5.1E-01 6.8E-01 0.0029 4.4E-01 6.3E-01 0.0028 4.6E-01 6.4E-01 0.0025 5.2E-01 6.8E-01 0.0009 8.1E-01 8.9E-01 0.0025 5.1E-01 6.7E-01 0.0025 5.1E-01 7.1E-01 verrucomicrobiales order 0.0024 5.3E-01 9.0E-01 0.0025 5.1E-01 7.7E-01 0.0029 4.4E-01 7.0E-01 0.0028 4.6E-01 7.5E-01 0.0025 5.2E-01 7.7E-01 0.0009 8.1E-01 8.9E-01 0.0025 5.1E-01 7.5E-01 0.0025 5.1E-01 7.5E-01 verrucomicrobiae class 0.0024 5.3E-01 7.7E-01 0.0025 5.1E-01 8.6E-01 0.0029 4.4E-01 7.7E-01 0.0028 4.6E-01 7.8E-01 0.0025 5.2E-01 8.1E-01 0.0009 8.1E-01 9.7E-01 0.0025 5.1E-01 7.9E-01 0.0025 5.1E-01 8.0E-01 verrucomicrobia phylum 0.0024 5.3E-01 8.5E-01 0.0025 5.1E-01 8.5E-01 0.0029 4.4E-01 7.7E-01 0.0028 4.6E-01 7.8E-01 0.0025 5.2E-01 8.8E-01 0.0009 8.1E-01 8.1E-01 0.0025 5.1E-01 8.4E-01 0.0025 5.1E-01 8.0E-01 parabacteroides_merdae_unclassified strain 0.0016 3.9E-01 6.8E-01 0.0012 5.1E-01 7.7E-01 0.0014 4.7E-01 7.6E-01 0.0014 4.5E-01 7.6E-01 0.0016 4.0E-01 7.2E-01 0.0010 6.0E-01 8.0E-01 0.0013 4.8E-01 7.7E-01 0.0013 4.7E-01 7.7E-01 parabacteroides_merdae species 0.0016 3.9E-01 6.8E-01 0.0012 5.1E-01 8.1E-01 0.0014 4.7E-01 8.0E-01 0.0014 4.5E-01 7.8E-01 0.0016 4.0E-01 7.5E-01 0.0010 6.0E-01 8.4E-01 0.0013 4.8E-01 7.9E-01 0.0013 4.7E-01 8.0E-01 gcf_000473955 strain 0.0003 4.7E-01 7.4E-01 0.0003 5.1E-01 7.7E-01 0.0003 4.8E-01 7.7E-01 0.0003 5.0E-01 7.8E-01 0.0002 6.7E-01 8.5E-01 0.0003 4.9E-01 7.4E-01 0.0003 5.2E-01 7.9E-01 0.0003 5.1E-01 7.7E-01 coprobacter_fastidiosus species 0.0003 4.7E-01 7.4E-01 0.0003 5.1E-01 8.1E-01 0.0003 4.8E-01 8.2E-01 0.0003 5.0E-01 8.1E-01 0.0002 6.7E-01 9.0E-01 0.0003 4.9E-01 7.8E-01 0.0003 5.2E-01 8.2E-01 0.0003 5.1E-01 8.0E-01 coprobacter genus 0.0003 4.7E-01 7.6E-01 0.0003 5.1E-01 8.3E-01 0.0003 4.8E-01 7.9E-01 0.0003 5.0E-01 8.3E-01 0.0002 6.7E-01 9.0E-01 0.0003 4.9E-01 8.1E-01 0.0003 5.2E-01 7.7E-01 0.0003 5.1E-01 8.0E-01 streptococcaceae family 0.0018 4.7E-01 6.8E-01 0.0016 5.2E-01 6.8E-01 0.0011 6.6E-01 6.9E-01 0.0013 6.1E-01 7.1E-01 0.0013 6.2E-01 6.9E-01 0.0007 7.8E-01 8.9E-01 0.0010 7.0E-01 7.5E-01 0.0012 6.4E-01 7.1E-01 gcf_000174195 strain 0.0010 5.6E-01 8.1E-01 0.0011 5.2E-01 7.7E-01 0.0011 5.2E-01 7.8E-01 0.0011 5.2E-01 7.9E-01 0.0011 5.2E-01 8.3E-01 0.0015 4.0E-01 7.4E-01 0.0011 5.3E-01 7.9E-01 0.0011 5.5E-01 7.8E-01 roseburia_inulinivorans species 0.0010 5.6E-01 8.1E-01 0.0011 5.2E-01 8.1E-01 0.0011 5.2E-01 8.3E-01 0.0011 5.2E-01 8.2E-01 0.0011 5.2E-01 8.4E-01 0.0015 4.0E-01 7.7E-01 0.0011 5.3E-01 8.2E-01 0.0011 5.5E-01 8.1E-01 ruminococcus_obeum_unclassified strain -0.0010 4.7E-01 7.4E-01 -0.0009 5.2E-01 7.7E-01 -0.0013 3.5E-01 6.6E-01 -0.0011 4.4E-01 7.6E-01 -0.0010 5.1E-01 8.3E-01 -0.0008 6.0E-01 8.0E-01 -0.0011 4.6E-01 7.7E-01 -0.0011 4.6E-01 7.7E-01 bacteroides_xylanisolvens_unclassified strain 0.0004 7.2E-01 8.8E-01 0.0006 5.3E-01 7.7E-01 0.0004 7.1E-01 8.7E-01 0.0005 6.0E-01 8.2E-01 0.0004 6.7E-01 8.5E-01 0.0008 4.6E-01 7.4E-01 0.0006 5.5E-01 7.9E-01 0.0006 5.6E-01 7.8E-01 bacteroides_xylanisolvens species 0.0004 7.2E-01 8.9E-01 0.0006 5.3E-01 8.1E-01 0.0004 7.1E-01 8.9E-01 0.0005 6.0E-01 8.5E-01 0.0004 6.7E-01 9.0E-01 0.0008 4.6E-01 7.8E-01 0.0006 5.5E-01 8.3E-01 0.0006 5.6E-01 8.1E-01 gcf_000210555 strain 0.0005 5.1E-01 7.8E-01 0.0005 5.4E-01 7.7E-01 0.0003 7.3E-01 8.7E-01 0.0004 6.4E-01 8.4E-01 0.0005 5.6E-01 8.5E-01 0.0005 5.1E-01 7.5E-01 0.0004 6.1E-01 8.2E-01 0.0004 6.1E-01 8.2E-01 coprococcus_catus species 0.0005 5.1E-01 7.9E-01 0.0005 5.4E-01 8.1E-01 0.0003 7.3E-01 8.9E-01 0.0004 6.4E-01 8.5E-01 0.0005 5.6E-01 8.5E-01 0.0005 5.1E-01 7.9E-01 0.0004 6.1E-01 8.4E-01 0.0004 6.1E-01 8.5E-01 collinsella genus -0.0018 3.3E-01 6.5E-01 -0.0011 5.4E-01 8.3E-01 -0.0017 3.7E-01 7.4E-01 -0.0015 4.1E-01 7.6E-01 -0.0014 4.6E-01 8.5E-01 -0.0013 4.8E-01 8.1E-01 -0.0015 4.2E-01 7.7E-01 -0.0015 4.2E-01 7.8E-01 ruminococcus_gnavus_unclassified strain -0.0007 6.9E-01 8.7E-01 -0.0011 5.4E-01 7.7E-01 -0.0006 7.4E-01 8.7E-01 -0.0010 5.8E-01 8.0E-01 -0.0008 6.4E-01 8.5E-01 -0.0005 7.9E-01 8.9E-01 -0.0010 5.6E-01 7.9E-01 -0.0010 5.5E-01 7.8E-01 ruminococcus_gnavus species -0.0007 6.9E-01 8.9E-01 -0.0011 5.4E-01 8.1E-01 -0.0006 7.4E-01 8.9E-01 -0.0010 5.8E-01 8.5E-01 -0.0008 6.4E-01 9.0E-01 -0.0005 7.9E-01 9.0E-01 -0.0010 5.6E-01 8.3E-01 -0.0010 5.5E-01 8.1E-01 parabacteroides_johnsonii_unclassified strain 0.0006 4.9E-01 7.6E-01 0.0006 5.4E-01 7.7E-01 0.0006 5.0E-01 7.7E-01 0.0005 5.7E-01 8.0E-01 0.0005 6.0E-01 8.5E-01 0.0014 1.6E-01 5.5E-01 0.0005 5.7E-01 7.9E-01 0.0005 5.6E-01 7.9E-01 turicibacter genus -0.0003 5.3E-01 7.9E-01 -0.0003 5.4E-01 8.3E-01 -0.0003 5.6E-01 8.1E-01 -0.0003 5.5E-01 8.3E-01 -0.0003 5.4E-01 8.5E-01 -0.0004 4.2E-01 8.1E-01 -0.0003 5.3E-01 7.7E-01 -0.0003 5.3E-01 8.0E-01 gcf_000210055 strain 0.0005 3.2E-01 6.1E-01 0.0003 5.4E-01 7.7E-01 0.0003 5.9E-01 8.4E-01 0.0003 6.3E-01 8.3E-01 0.0002 7.7E-01 9.0E-01 0.0002 7.8E-01 8.8E-01 0.0002 6.5E-01 8.5E-01 0.0003 6.1E-01 8.2E-01 gordonibacter_pamelaeae species 0.0005 3.2E-01 6.5E-01 0.0003 5.4E-01 8.1E-01 0.0003 5.9E-01 8.7E-01 0.0003 6.3E-01 8.5E-01 0.0002 7.7E-01 9.2E-01 0.0002 7.8E-01 9.0E-01 0.0002 6.5E-01 8.8E-01 0.0003 6.1E-01 8.5E-01 gordonibacter genus 0.0005 3.2E-01 6.5E-01 0.0003 5.4E-01 8.3E-01 0.0003 5.9E-01 8.1E-01 0.0003 6.3E-01 8.3E-01 0.0002 7.7E-01 9.4E-01 0.0002 7.8E-01 9.4E-01 0.0002 6.5E-01 8.5E-01 0.0003 6.1E-01 8.1E-01 paraprevotella genus 0.0011 4.1E-01 7.3E-01 0.0008 5.4E-01 8.3E-01 0.0006 6.4E-01 8.2E-01 0.0008 5.5E-01 8.3E-01 0.0009 4.9E-01 8.5E-01 -0.0001 9.3E-01 9.8E-01 0.0009 5.1E-01 7.7E-01 0.0009 5.1E-01 8.0E-01 paraprevotella_unclassified species 0.0008 4.3E-01 7.1E-01 0.0006 5.5E-01 8.1E-01 0.0004 6.8E-01 8.9E-01 0.0006 5.7E-01 8.5E-01 0.0007 5.1E-01 8.4E-01 0.0000 9.7E-01 9.8E-01 0.0007 5.3E-01 8.2E-01 0.0007 5.2E-01 8.1E-01 gcf_000209405 strain 0.0002 8.8E-01 9.4E-01 0.0007 5.5E-01 7.8E-01 0.0006 5.9E-01 8.4E-01 0.0008 4.9E-01 7.7E-01 0.0009 4.3E-01 7.5E-01 0.0009 4.5E-01 7.4E-01 0.0007 5.2E-01 7.9E-01 0.0007 5.1E-01 7.7E-01 lachnospiraceae_bacterium_3_1_46faa species 0.0002 8.8E-01 9.5E-01 0.0007 5.5E-01 8.1E-01 0.0006 5.9E-01 8.7E-01 0.0008 4.9E-01 8.0E-01 0.0009 4.3E-01 7.6E-01 0.0009 4.5E-01 7.8E-01 0.0007 5.2E-01 8.2E-01 0.0007 5.1E-01 8.0E-01 eubacterium_siraeum species 0.0013 7.7E-01 9.0E-01 0.0027 5.6E-01 8.1E-01 0.0023 6.2E-01 8.8E-01 0.0021 6.4E-01 8.5E-01 0.0028 5.4E-01 8.5E-01 0.0012 7.9E-01 9.0E-01 0.0025 5.8E-01 8.3E-01 0.0026 5.7E-01 8.2E-01 c2likevirus genus -0.0003 8.5E-01 9.2E-01 -0.0008 5.6E-01 8.3E-01 -0.0006 6.5E-01 8.2E-01 -0.0007 6.0E-01 8.3E-01 -0.0007 6.2E-01 8.8E-01 -0.0004 8.0E-01 9.4E-01 -0.0008 5.7E-01 7.7E-01 -0.0008 5.8E-01 8.0E-01 coriobacteriaceae family 0.0005 7.9E-01 8.8E-01 0.0010 5.6E-01 7.1E-01 0.0009 5.9E-01 6.9E-01 0.0008 6.6E-01 7.2E-01 0.0011 5.4E-01 6.8E-01 0.0006 7.4E-01 8.9E-01 0.0007 7.0E-01 7.5E-01 0.0007 6.9E-01 7.4E-01 coriobacteriales order 0.0005 7.9E-01 9.1E-01 0.0010 5.6E-01 7.7E-01 0.0009 5.9E-01 7.0E-01 0.0008 6.6E-01 7.5E-01 0.0011 5.4E-01 7.7E-01 0.0006 7.4E-01 8.9E-01 0.0007 7.0E-01 7.5E-01 0.0007 6.9E-01 7.5E-01 gcf_000169035 strain -0.0016 3.8E-01 6.7E-01 -0.0010 5.7E-01 7.8E-01 -0.0018 3.4E-01 6.6E-01 -0.0016 4.0E-01 7.5E-01 -0.0015 4.4E-01 7.7E-01 -0.0013 4.9E-01 7.4E-01 -0.0015 4.3E-01 7.4E-01 -0.0015 4.3E-01 7.7E-01 collinsella_aerofaciens species -0.0016 3.8E-01 6.8E-01 -0.0010 5.7E-01 8.1E-01 -0.0018 3.4E-01 6.9E-01 -0.0016 4.0E-01 7.6E-01 -0.0015 4.4E-01 7.8E-01 -0.0013 4.9E-01 7.8E-01 -0.0015 4.3E-01 7.7E-01 -0.0015 4.3E-01 7.8E-01 anaerotruncus genus 0.0004 5.4E-01 7.9E-01 0.0004 5.8E-01 8.4E-01 0.0003 6.2E-01 8.2E-01 0.0003 6.0E-01 8.3E-01 0.0004 5.4E-01 8.5E-01 0.0003 6.3E-01 8.6E-01 0.0005 4.9E-01 7.7E-01 0.0004 5.6E-01 8.0E-01 gcf_000185545 strain 0.0001 9.2E-01 9.4E-01 0.0007 5.8E-01 8.0E-01 0.0009 5.2E-01 7.8E-01 0.0008 5.7E-01 8.0E-01 0.0008 5.5E-01 8.5E-01 0.0006 6.4E-01 8.0E-01 0.0005 7.1E-01 8.8E-01 0.0006 6.5E-01 8.4E-01 lachnospiraceae_bacterium_8_1_57faa species 0.0001 9.2E-01 9.5E-01 0.0007 5.8E-01 8.3E-01 0.0009 5.2E-01 8.3E-01 0.0008 5.7E-01 8.5E-01 0.0008 5.5E-01 8.5E-01 0.0006 6.4E-01 8.5E-01 0.0005 7.1E-01 8.8E-01 0.0006 6.5E-01 8.6E-01 caudovirales order -0.0005 7.7E-01 9.1E-01 -0.0010 5.9E-01 7.7E-01 -0.0009 6.5E-01 7.0E-01 -0.0010 6.1E-01 7.5E-01 -0.0009 6.5E-01 7.7E-01 -0.0010 6.2E-01 8.9E-01 -0.0010 6.0E-01 7.5E-01 -0.0010 6.0E-01 7.5E-01 18

Supplementary Data 1b MV + renal function MV + pre-DM and MV & Exclude DM MV + FFQ MV + DDR (5d avg) MV + DDR (2d avg) Taxonom Basic Model MV + HBA1c Taxonomic label indicator DM status patients phosphorus intake phosphorus intake phosphorus intake ic type Effect P FDR Effect P FDR Effect P FDR Effect P FDR Effect P FDR Effect P FDR Effect P FDR Effect P FDR acidaminococcus_unclassified species 0.0007 3.9E-01 6.8E-01 0.0004 6.0E-01 8.4E-01 0.0002 8.3E-01 9.2E-01 0.0004 6.0E-01 8.5E-01 -0.0001 8.8E-01 9.6E-01 0.0005 5.8E-01 8.4E-01 0.0004 6.1E-01 8.4E-01 0.0004 6.0E-01 8.4E-01 gcf_000273175 strain -0.0006 2.2E-01 5.5E-01 -0.0002 6.0E-01 8.1E-01 -0.0002 6.7E-01 8.7E-01 -0.0002 6.0E-01 8.2E-01 -0.0001 8.4E-01 9.1E-01 -0.0002 6.1E-01 8.0E-01 -0.0002 6.0E-01 8.2E-01 -0.0002 6.0E-01 8.2E-01 bacteroides_nordii species -0.0006 2.2E-01 5.9E-01 -0.0002 6.0E-01 8.4E-01 -0.0002 6.7E-01 8.9E-01 -0.0002 6.0E-01 8.5E-01 -0.0001 8.4E-01 9.3E-01 -0.0002 6.1E-01 8.4E-01 -0.0002 6.0E-01 8.4E-01 -0.0002 6.0E-01 8.4E-01 holdemania_unclassified species 0.0001 7.4E-01 8.9E-01 0.0002 6.1E-01 8.4E-01 0.0001 7.7E-01 8.9E-01 0.0001 7.0E-01 8.6E-01 0.0000 9.5E-01 9.9E-01 0.0001 7.5E-01 8.9E-01 0.0002 6.4E-01 8.8E-01 0.0002 6.4E-01 8.6E-01 coprococcus genus -0.0038 2.0E-01 5.7E-01 -0.0015 6.2E-01 8.7E-01 -0.0021 4.9E-01 7.9E-01 -0.0016 5.8E-01 8.3E-01 -0.0012 6.9E-01 9.0E-01 -0.0005 8.7E-01 9.7E-01 -0.0018 5.4E-01 7.7E-01 -0.0016 5.9E-01 8.0E-01 clostridiales order 0.0022 7.0E-01 9.1E-01 0.0029 6.2E-01 7.7E-01 0.0028 6.3E-01 7.0E-01 0.0027 6.4E-01 7.5E-01 0.0025 6.6E-01 7.7E-01 0.0050 4.0E-01 8.9E-01 0.0028 6.3E-01 7.5E-01 0.0031 6.0E-01 7.5E-01 clostridia class 0.0022 7.0E-01 7.7E-01 0.0029 6.2E-01 8.6E-01 0.0028 6.3E-01 7.7E-01 0.0027 6.4E-01 7.8E-01 0.0025 6.6E-01 8.8E-01 0.0050 4.0E-01 8.1E-01 0.0028 6.3E-01 8.4E-01 0.0031 6.0E-01 8.0E-01 firmicutes phylum 0.0020 7.3E-01 8.5E-01 0.0028 6.3E-01 8.5E-01 0.0028 6.3E-01 7.7E-01 0.0026 6.5E-01 7.8E-01 0.0024 6.8E-01 8.8E-01 0.0044 4.5E-01 7.9E-01 0.0024 6.8E-01 8.4E-01 0.0027 6.4E-01 8.0E-01 gcf_000190535 strain -0.0008 6.2E-01 8.3E-01 -0.0008 6.3E-01 8.4E-01 -0.0007 6.7E-01 8.7E-01 -0.0008 6.2E-01 8.2E-01 -0.0004 8.2E-01 9.1E-01 -0.0011 5.0E-01 7.4E-01 -0.0005 7.6E-01 8.9E-01 -0.0006 7.0E-01 8.7E-01 odoribacter_splanchnicus species -0.0008 6.2E-01 8.6E-01 -0.0008 6.3E-01 8.6E-01 -0.0007 6.7E-01 8.9E-01 -0.0008 6.2E-01 8.5E-01 -0.0004 8.2E-01 9.3E-01 -0.0011 5.0E-01 7.8E-01 -0.0005 7.6E-01 8.9E-01 -0.0006 7.0E-01 8.8E-01 faecalibacterium_prausnitzii_unclassified strain -0.0016 6.0E-01 8.3E-01 -0.0015 6.4E-01 8.4E-01 -0.0024 4.6E-01 7.6E-01 -0.0020 5.2E-01 7.9E-01 -0.0015 6.4E-01 8.5E-01 -0.0018 5.8E-01 8.0E-01 -0.0019 5.4E-01 7.9E-01 -0.0019 5.4E-01 7.8E-01 streptococcus_parasanguinis_unclassified strain 0.0006 5.8E-01 8.3E-01 0.0005 6.5E-01 8.5E-01 0.0004 7.0E-01 8.7E-01 0.0005 6.5E-01 8.4E-01 0.0005 6.8E-01 8.5E-01 0.0006 5.8E-01 8.0E-01 0.0003 7.6E-01 8.9E-01 0.0004 7.2E-01 8.9E-01 streptococcus_parasanguinis species 0.0006 5.8E-01 8.3E-01 0.0005 6.5E-01 8.7E-01 0.0004 7.0E-01 8.9E-01 0.0005 6.5E-01 8.5E-01 0.0005 6.8E-01 9.0E-01 0.0006 5.8E-01 8.4E-01 0.0003 7.6E-01 8.9E-01 0.0004 7.2E-01 8.9E-01 enterobacteriaceae family 0.0023 3.8E-01 6.8E-01 0.0012 6.5E-01 7.6E-01 0.0017 5.2E-01 6.8E-01 0.0014 6.1E-01 7.1E-01 0.0015 5.8E-01 6.9E-01 0.0005 8.4E-01 8.9E-01 0.0013 6.2E-01 7.2E-01 0.0013 6.3E-01 7.1E-01 enterobacteriales order 0.0023 3.8E-01 9.0E-01 0.0012 6.5E-01 7.7E-01 0.0017 5.2E-01 7.0E-01 0.0014 6.1E-01 7.5E-01 0.0015 5.8E-01 7.7E-01 0.0005 8.4E-01 8.9E-01 0.0013 6.2E-01 7.5E-01 0.0013 6.3E-01 7.5E-01 eubacterium_siraeum_unclassified strain 0.0004 9.3E-01 9.4E-01 0.0020 6.6E-01 8.5E-01 0.0017 7.0E-01 8.7E-01 0.0016 7.3E-01 8.7E-01 0.0023 6.1E-01 8.5E-01 0.0006 9.0E-01 9.4E-01 0.0019 6.7E-01 8.6E-01 0.0019 6.6E-01 8.4E-01 streptococcus genus 0.0013 6.0E-01 8.2E-01 0.0011 6.6E-01 9.0E-01 0.0005 8.3E-01 9.6E-01 0.0008 7.6E-01 9.0E-01 0.0007 7.9E-01 9.4E-01 0.0002 9.5E-01 9.8E-01 0.0004 8.6E-01 9.3E-01 0.0006 8.0E-01 9.3E-01 roseburia_unclassified species -0.0013 2.9E-01 6.1E-01 -0.0006 6.6E-01 8.7E-01 -0.0008 5.5E-01 8.6E-01 -0.0007 6.1E-01 8.5E-01 -0.0007 5.9E-01 8.9E-01 -0.0005 7.0E-01 8.9E-01 -0.0005 6.7E-01 8.8E-01 -0.0006 6.6E-01 8.7E-01 bacteroides_fragilis species -0.0010 5.7E-01 8.2E-01 -0.0007 6.6E-01 8.7E-01 -0.0008 6.6E-01 8.9E-01 -0.0009 5.9E-01 8.5E-01 -0.0009 6.1E-01 9.0E-01 -0.0010 5.9E-01 8.4E-01 -0.0010 5.6E-01 8.3E-01 -0.0010 5.6E-01 8.1E-01 gcf_000469345 strain -0.0008 4.3E-01 7.2E-01 -0.0004 6.7E-01 8.5E-01 -0.0008 4.7E-01 7.6E-01 -0.0005 6.1E-01 8.2E-01 -0.0004 6.8E-01 8.5E-01 0.0002 8.8E-01 9.4E-01 -0.0004 6.8E-01 8.6E-01 -0.0004 6.6E-01 8.4E-01 eubacterium_ramulus species -0.0008 4.3E-01 7.1E-01 -0.0004 6.7E-01 8.7E-01 -0.0008 4.7E-01 8.0E-01 -0.0005 6.1E-01 8.5E-01 -0.0004 6.8E-01 9.0E-01 0.0002 8.8E-01 9.6E-01 -0.0004 6.8E-01 8.8E-01 -0.0004 6.6E-01 8.7E-01 escherichia_coli_unclassified strain -0.0003 9.0E-01 9.4E-01 -0.0011 6.7E-01 8.5E-01 -0.0008 7.7E-01 8.7E-01 -0.0010 6.9E-01 8.5E-01 -0.0005 8.6E-01 9.3E-01 -0.0008 7.6E-01 8.7E-01 -0.0011 6.7E-01 8.6E-01 -0.0011 6.8E-01 8.5E-01 escherichia_coli species -0.0003 9.0E-01 9.5E-01 -0.0011 6.7E-01 8.7E-01 -0.0008 7.7E-01 8.9E-01 -0.0010 6.9E-01 8.6E-01 -0.0005 8.6E-01 9.5E-01 -0.0008 7.6E-01 8.9E-01 -0.0011 6.7E-01 8.8E-01 -0.0011 6.8E-01 8.7E-01 escherichia genus -0.0003 9.1E-01 9.2E-01 -0.0011 6.8E-01 9.0E-01 -0.0007 7.9E-01 9.4E-01 -0.0010 7.1E-01 8.8E-01 -0.0004 8.7E-01 9.6E-01 -0.0007 8.1E-01 9.4E-01 -0.0011 6.9E-01 8.9E-01 -0.0011 6.9E-01 8.8E-01 desulfovibrio_desulfuricans_unclassified strain -0.0002 6.7E-01 8.7E-01 -0.0002 6.8E-01 8.5E-01 -0.0002 7.3E-01 8.7E-01 -0.0002 6.9E-01 8.5E-01 -0.0002 6.8E-01 8.5E-01 -0.0002 6.2E-01 8.0E-01 -0.0001 8.2E-01 9.0E-01 -0.0001 7.6E-01 8.9E-01 coprobacillus_unclassified species 0.0004 5.4E-01 8.1E-01 0.0003 6.9E-01 8.7E-01 0.0004 5.6E-01 8.6E-01 0.0003 7.2E-01 8.6E-01 0.0002 7.4E-01 9.1E-01 0.0006 4.4E-01 7.8E-01 0.0003 7.1E-01 8.8E-01 0.0002 7.5E-01 8.9E-01 coprobacillus genus 0.0004 5.4E-01 7.9E-01 0.0003 6.9E-01 9.0E-01 0.0004 5.6E-01 8.1E-01 0.0003 7.2E-01 8.8E-01 0.0002 7.4E-01 9.3E-01 0.0006 4.4E-01 8.1E-01 0.0003 7.1E-01 9.0E-01 0.0002 7.5E-01 9.2E-01 c2likevirus_unclassified species 0.0000 9.8E-01 9.9E-01 -0.0005 6.9E-01 8.7E-01 -0.0004 7.8E-01 8.9E-01 -0.0005 7.2E-01 8.6E-01 -0.0005 7.4E-01 9.1E-01 -0.0001 9.5E-01 9.7E-01 -0.0005 6.9E-01 8.8E-01 -0.0005 7.1E-01 8.8E-01 clostridium_bolteae_unclassified strain 0.0003 6.1E-01 8.3E-01 0.0002 6.9E-01 8.5E-01 0.0002 6.7E-01 8.7E-01 0.0002 6.6E-01 8.4E-01 0.0002 6.9E-01 8.5E-01 0.0004 4.8E-01 7.4E-01 0.0003 6.2E-01 8.3E-01 0.0003 6.4E-01 8.4E-01 lachnospiraceae_noname genus 0.0003 8.7E-01 9.2E-01 0.0007 7.0E-01 9.0E-01 0.0011 5.7E-01 8.1E-01 0.0008 6.9E-01 8.8E-01 0.0009 6.4E-01 8.8E-01 0.0010 6.0E-01 8.5E-01 0.0006 7.5E-01 9.3E-01 0.0007 7.0E-01 8.8E-01 actinomycetales order -0.0001 8.5E-01 9.1E-01 -0.0002 7.0E-01 7.7E-01 -0.0003 5.7E-01 7.0E-01 -0.0003 5.7E-01 7.5E-01 -0.0004 5.5E-01 7.7E-01 -0.0004 5.2E-01 8.9E-01 -0.0003 6.7E-01 7.5E-01 -0.0002 7.0E-01 7.5E-01 peptostreptococcaceae family 0.0002 8.9E-01 9.2E-01 0.0005 7.0E-01 7.6E-01 0.0007 5.6E-01 6.8E-01 0.0006 6.1E-01 7.1E-01 0.0006 6.0E-01 6.9E-01 0.0005 6.5E-01 8.2E-01 0.0003 8.0E-01 8.3E-01 0.0004 7.5E-01 7.7E-01 bacteroides_stercoris species -0.0004 9.1E-01 9.5E-01 -0.0012 7.0E-01 8.7E-01 -0.0015 6.2E-01 8.8E-01 -0.0012 7.0E-01 8.6E-01 -0.0029 2.8E-01 5.9E-01 -0.0020 5.2E-01 7.9E-01 -0.0010 7.4E-01 8.8E-01 -0.0009 7.6E-01 8.9E-01 gcf_000233955 strain 0.0005 5.2E-01 7.8E-01 0.0003 7.0E-01 8.5E-01 0.0002 7.6E-01 8.7E-01 0.0003 6.8E-01 8.5E-01 0.0004 6.3E-01 8.5E-01 -0.0003 6.7E-01 8.3E-01 0.0003 6.5E-01 8.5E-01 0.0003 6.5E-01 8.4E-01 paraprevotella_clara species 0.0005 5.2E-01 7.9E-01 0.0003 7.0E-01 8.7E-01 0.0002 7.6E-01 8.9E-01 0.0003 6.8E-01 8.6E-01 0.0004 6.3E-01 9.0E-01 -0.0003 6.7E-01 8.8E-01 0.0003 6.5E-01 8.8E-01 0.0003 6.5E-01 8.6E-01 streptococcus_thermophilus_unclassified strain 0.0005 7.1E-01 8.8E-01 0.0006 7.0E-01 8.5E-01 0.0003 8.3E-01 9.0E-01 0.0002 9.0E-01 9.4E-01 0.0000 9.9E-01 1.0E+00 -0.0005 7.4E-01 8.7E-01 0.0001 9.5E-01 9.6E-01 0.0002 9.0E-01 9.4E-01 streptococcus_thermophilus species 0.0005 7.1E-01 8.9E-01 0.0006 7.0E-01 8.7E-01 0.0003 8.3E-01 9.2E-01 0.0002 9.0E-01 9.5E-01 0.0000 9.9E-01 1.0E+00 -0.0005 7.4E-01 8.9E-01 0.0001 9.5E-01 9.8E-01 0.0002 9.0E-01 9.6E-01 desulfovibrionaceae family 0.0009 4.6E-01 6.8E-01 0.0004 7.0E-01 7.6E-01 0.0005 6.6E-01 6.9E-01 0.0005 7.0E-01 7.3E-01 0.0007 5.4E-01 6.8E-01 0.0002 8.9E-01 8.9E-01 0.0008 4.9E-01 6.7E-01 0.0006 6.1E-01 7.1E-01 desulfovibrionales order 0.0009 4.6E-01 9.0E-01 0.0004 7.0E-01 7.7E-01 0.0005 6.6E-01 7.0E-01 0.0005 7.0E-01 7.5E-01 0.0007 5.4E-01 7.7E-01 0.0002 8.9E-01 8.9E-01 0.0008 4.9E-01 7.5E-01 0.0006 6.1E-01 7.5E-01 deltaproteobacteria class 0.0009 4.6E-01 7.7E-01 0.0004 7.0E-01 8.6E-01 0.0005 6.6E-01 7.7E-01 0.0005 7.0E-01 7.8E-01 0.0007 5.4E-01 8.1E-01 0.0002 8.9E-01 9.7E-01 0.0008 4.9E-01 7.9E-01 0.0006 6.1E-01 8.0E-01 bifidobacteriaceae family -0.0019 6.0E-01 7.0E-01 -0.0014 7.1E-01 7.6E-01 -0.0023 5.4E-01 6.8E-01 -0.0019 6.0E-01 7.1E-01 -0.0013 7.3E-01 7.5E-01 -0.0021 5.7E-01 8.2E-01 -0.0021 5.6E-01 7.0E-01 -0.0020 5.9E-01 7.1E-01 bifidobacteriales order -0.0019 6.0E-01 9.0E-01 -0.0014 7.1E-01 7.7E-01 -0.0023 5.4E-01 7.0E-01 -0.0019 6.0E-01 7.5E-01 -0.0013 7.3E-01 7.8E-01 -0.0021 5.7E-01 8.9E-01 -0.0021 5.6E-01 7.5E-01 -0.0020 5.9E-01 7.5E-01 turicibacter_unclassified species -0.0002 7.0E-01 8.9E-01 -0.0002 7.1E-01 8.7E-01 -0.0002 7.1E-01 8.9E-01 -0.0001 7.2E-01 8.6E-01 -0.0002 7.0E-01 9.1E-01 -0.0002 5.9E-01 8.4E-01 -0.0002 7.0E-01 8.8E-01 -0.0002 7.0E-01 8.8E-01 bifidobacterium genus -0.0018 6.1E-01 8.2E-01 -0.0013 7.2E-01 9.0E-01 -0.0022 5.5E-01 8.1E-01 -0.0019 6.1E-01 8.3E-01 -0.0013 7.4E-01 9.3E-01 -0.0021 5.7E-01 8.3E-01 -0.0021 5.7E-01 7.7E-01 -0.0019 5.9E-01 8.0E-01 methanobrevibacter_unclassified species -0.0004 6.6E-01 8.9E-01 -0.0003 7.2E-01 8.8E-01 -0.0003 7.3E-01 8.9E-01 -0.0002 8.0E-01 9.2E-01 -0.0004 6.3E-01 9.0E-01 -0.0002 8.5E-01 9.4E-01 -0.0002 7.9E-01 9.1E-01 -0.0002 7.8E-01 9.1E-01 bacteroidetes phylum -0.0003 9.5E-01 9.5E-01 -0.0020 7.3E-01 8.5E-01 -0.0019 7.4E-01 7.7E-01 -0.0018 7.6E-01 7.8E-01 -0.0013 8.2E-01 8.8E-01 -0.0025 6.7E-01 7.9E-01 -0.0010 8.6E-01 8.6E-01 -0.0015 8.0E-01 8.0E-01 bacteroidales order -0.0003 9.5E-01 9.5E-01 -0.0020 7.3E-01 7.7E-01 -0.0019 7.4E-01 7.4E-01 -0.0018 7.6E-01 7.6E-01 -0.0013 8.2E-01 8.2E-01 -0.0025 6.7E-01 8.9E-01 -0.0010 8.6E-01 8.6E-01 -0.0015 8.0E-01 8.0E-01 bacteroidia class -0.0003 9.5E-01 9.5E-01 -0.0020 7.3E-01 8.6E-01 -0.0019 7.4E-01 7.7E-01 -0.0018 7.6E-01 7.8E-01 -0.0013 8.2E-01 8.8E-01 -0.0025 6.7E-01 9.1E-01 -0.0010 8.6E-01 8.6E-01 -0.0015 8.0E-01 8.0E-01 bacteroides_eggerthii_unclassified strain 0.0003 9.3E-01 9.4E-01 0.0010 7.3E-01 8.7E-01 0.0011 7.1E-01 8.7E-01 0.0008 7.6E-01 8.8E-01 0.0009 7.6E-01 9.0E-01 0.0014 6.2E-01 8.0E-01 0.0010 7.3E-01 8.9E-01 0.0009 7.5E-01 8.9E-01 bacteroides_eggerthii species 0.0003 9.3E-01 9.5E-01 0.0010 7.3E-01 8.8E-01 0.0011 7.1E-01 8.9E-01 0.0008 7.6E-01 9.0E-01 0.0009 7.6E-01 9.1E-01 0.0014 6.2E-01 8.4E-01 0.0010 7.3E-01 8.8E-01 0.0009 7.5E-01 8.9E-01 bacteroides_caccae_unclassified strain 0.0008 7.0E-01 8.7E-01 0.0007 7.3E-01 8.7E-01 0.0002 9.1E-01 9.4E-01 0.0003 8.9E-01 9.4E-01 0.0009 6.6E-01 8.5E-01 0.0011 6.1E-01 8.0E-01 0.0004 8.5E-01 9.2E-01 0.0004 8.5E-01 9.1E-01 bacteroides_caccae species 0.0008 7.0E-01 8.9E-01 0.0007 7.3E-01 8.8E-01 0.0002 9.1E-01 9.6E-01 0.0003 8.9E-01 9.5E-01 0.0009 6.6E-01 9.0E-01 0.0011 6.1E-01 8.4E-01 0.0004 8.5E-01 9.3E-01 0.0004 8.5E-01 9.4E-01 haemophilus genus -0.0009 3.8E-01 6.9E-01 -0.0003 7.3E-01 9.0E-01 -0.0006 5.9E-01 8.1E-01 -0.0005 6.3E-01 8.3E-01 -0.0005 6.2E-01 8.8E-01 -0.0006 5.5E-01 8.3E-01 -0.0006 5.5E-01 7.7E-01 -0.0006 5.6E-01 8.0E-01 streptococcus_australis_unclassified strain 0.0002 7.6E-01 8.9E-01 0.0002 7.4E-01 8.7E-01 0.0001 8.0E-01 8.8E-01 0.0002 7.1E-01 8.6E-01 0.0002 6.7E-01 8.5E-01 0.0000 9.3E-01 9.6E-01 0.0001 8.2E-01 9.0E-01 0.0001 8.1E-01 9.0E-01 streptococcus_australis species 0.0002 7.6E-01 9.0E-01 0.0002 7.4E-01 8.8E-01 0.0001 8.0E-01 9.1E-01 0.0002 7.1E-01 8.6E-01 0.0002 6.7E-01 9.0E-01 0.0000 9.3E-01 9.7E-01 0.0001 8.2E-01 9.1E-01 0.0001 8.1E-01 9.2E-01 odoribacter genus -0.0007 6.8E-01 8.7E-01 -0.0005 7.4E-01 9.0E-01 -0.0006 7.0E-01 8.7E-01 -0.0005 7.4E-01 8.9E-01 -0.0003 8.8E-01 9.6E-01 -0.0011 5.1E-01 8.1E-01 -0.0003 8.4E-01 9.3E-01 -0.0004 8.0E-01 9.3E-01 ruminococcus_obeum species -0.0006 6.9E-01 8.9E-01 -0.0005 7.5E-01 8.8E-01 -0.0009 5.7E-01 8.7E-01 -0.0008 6.3E-01 8.5E-01 -0.0006 7.1E-01 9.1E-01 -0.0005 7.8E-01 9.0E-01 -0.0007 6.6E-01 8.8E-01 -0.0007 6.7E-01 8.7E-01 bacteroides_stercoris_unclassified strain -0.0001 9.7E-01 9.7E-01 -0.0009 7.6E-01 8.8E-01 -0.0013 6.7E-01 8.7E-01 -0.0010 7.5E-01 8.7E-01 -0.0027 3.1E-01 6.2E-01 -0.0018 5.6E-01 8.0E-01 -0.0008 7.9E-01 9.0E-01 -0.0008 8.0E-01 9.0E-01 alistipes_unclassified species 0.0000 9.9E-01 9.9E-01 0.0005 7.7E-01 8.9E-01 0.0005 7.5E-01 8.9E-01 0.0004 7.9E-01 9.2E-01 0.0005 7.9E-01 9.2E-01 0.0005 7.5E-01 8.9E-01 0.0006 7.3E-01 8.8E-01 0.0005 7.6E-01 8.9E-01 pasteurellaceae family -0.0008 4.3E-01 6.8E-01 -0.0003 7.7E-01 8.0E-01 -0.0005 6.2E-01 6.9E-01 -0.0004 6.7E-01 7.2E-01 -0.0005 6.6E-01 7.1E-01 -0.0005 6.0E-01 8.2E-01 -0.0006 5.9E-01 7.1E-01 -0.0005 6.0E-01 7.1E-01 pasteurellales order -0.0008 4.3E-01 9.0E-01 -0.0003 7.7E-01 7.7E-01 -0.0005 6.2E-01 7.0E-01 -0.0004 6.7E-01 7.5E-01 -0.0005 6.6E-01 7.7E-01 -0.0005 6.0E-01 8.9E-01 -0.0006 5.9E-01 7.5E-01 -0.0005 6.0E-01 7.5E-01 gcf_000154565 strain 0.0001 7.7E-01 8.9E-01 0.0001 7.7E-01 8.8E-01 0.0001 7.8E-01 8.7E-01 0.0001 8.4E-01 9.2E-01 0.0000 9.7E-01 9.9E-01 0.0001 8.5E-01 9.3E-01 0.0001 7.4E-01 8.9E-01 0.0001 8.5E-01 9.1E-01 anaerotruncus_colihominis species 0.0001 7.7E-01 9.0E-01 0.0001 7.7E-01 8.9E-01 0.0001 7.8E-01 8.9E-01 0.0001 8.4E-01 9.4E-01 0.0000 9.7E-01 1.0E+00 0.0001 8.5E-01 9.4E-01 0.0001 7.4E-01 8.8E-01 0.0001 8.5E-01 9.4E-01 haemophilus_parainfluenzae_unclassified strain -0.0008 4.1E-01 6.9E-01 -0.0003 7.8E-01 8.8E-01 -0.0005 6.2E-01 8.7E-01 -0.0004 6.6E-01 8.4E-01 -0.0004 6.6E-01 8.5E-01 -0.0005 5.9E-01 8.0E-01 -0.0005 5.8E-01 8.0E-01 -0.0005 5.9E-01 8.2E-01 haemophilus_parainfluenzae species -0.0008 4.1E-01 7.0E-01 -0.0003 7.8E-01 8.9E-01 -0.0005 6.2E-01 8.8E-01 -0.0004 6.6E-01 8.6E-01 -0.0004 6.6E-01 9.0E-01 -0.0005 5.9E-01 8.4E-01 -0.0005 5.8E-01 8.3E-01 -0.0005 5.9E-01 8.4E-01 gcf_000177015 strain -0.0002 7.3E-01 8.8E-01 -0.0002 7.8E-01 8.8E-01 -0.0003 6.1E-01 8.7E-01 -0.0004 5.6E-01 8.0E-01 -0.0004 5.3E-01 8.3E-01 -0.0005 4.4E-01 7.4E-01 -0.0004 5.7E-01 7.9E-01 -0.0004 5.5E-01 7.8E-01 ruminococcaceae_bacterium_d16 species -0.0002 7.3E-01 8.9E-01 -0.0002 7.8E-01 8.9E-01 -0.0003 6.1E-01 8.8E-01 -0.0004 5.6E-01 8.5E-01 -0.0004 5.3E-01 8.4E-01 -0.0005 4.4E-01 7.8E-01 -0.0004 5.7E-01 8.3E-01 -0.0004 5.5E-01 8.1E-01 ruminococcaceae_noname genus -0.0002 7.3E-01 8.9E-01 -0.0002 7.8E-01 9.2E-01 -0.0003 6.1E-01 8.2E-01 -0.0004 5.6E-01 8.3E-01 -0.0004 5.3E-01 8.5E-01 -0.0005 4.4E-01 8.1E-01 -0.0004 5.7E-01 7.7E-01 -0.0004 5.5E-01 8.0E-01 gcf_000162015 strain 0.0005 8.6E-01 9.4E-01 0.0008 7.8E-01 8.8E-01 0.0012 6.8E-01 8.7E-01 0.0010 7.5E-01 8.7E-01 0.0015 6.1E-01 8.5E-01 0.0001 9.6E-01 9.7E-01 0.0007 8.1E-01 9.0E-01 0.0009 7.7E-01 8.9E-01 19

Supplementary Data 2a Supplementary Data 2a. Associations of intakes of choline and red meat, or other TMAO precursors with TMAO levels, stratified by TMAO-associated abundant species, in full models and further adjusting for other TMAO precursors or TMAO predicting species. Full model was adjusted for age, BMI, physical activity, energy intake, smoking, cumulative dietary quality, antibiotics use, probiotics use, the Bristol Stool Chart, and/or fish intake (for non-fish dietary variables). Absence (species)/ Non- Presence (species)/ Stratified by Dietary Exposure Additionally conditioned on producer (mixed score) TMAO-producer (mixed P-interaction Taxa Abundance Prevalence Effect Se P n Effect Se P n Red meat intake - FFQ Alistipes shahii 1.02% 0.78 Fully adjusted -0.3849 0.1426 7.6E-03 199 0.1543 0.0736 3.6E-02 726 3.4E-02 Red meat intake - FFQ Alistipes shahii 1.02% 0.78 Choline intake - DDR -0.4016 0.1482 7.4E-03 199 0.1436 0.0733 5.0E-02 726 1.5E-02 Red meat intake - FFQ Alistipes shahii 1.02% 0.78 Choline intake - FFQ -0.4454 0.1453 2.5E-03 199 0.1531 0.0803 5.7E-02 726 1.9E-02 Red meat intake - FFQ Alistipes shahii 1.02% 0.78 Dairy intake - DDR -0.3699 0.1418 9.9E-03 199 0.1566 0.0738 3.4E-02 726 3.7E-02 Red meat intake - FFQ Alistipes shahii 1.02% 0.78 Dairy intake - FFQ -0.3586 0.1412 1.2E-02 199 0.1623 0.0737 2.8E-02 726 3.4E-02 Red meat intake - FFQ Alistipes shahii 1.02% 0.78 Egg intake - DDR -0.4254 0.1483 4.6E-03 199 0.1499 0.0738 4.3E-02 726 2.6E-02 Red meat intake - FFQ Alistipes shahii 1.02% 0.78 Egg intake - FFQ -0.3717 0.1425 9.8E-03 199 0.1307 0.0745 8.0E-02 726 4.9E-02 Red meat intake - FFQ Alistipes shahii 1.02% 0.78 Eubacterium biforme -0.3903 0.1411 6.3E-03 199 0.1539 0.0738 3.7E-02 726 3.3E-02 Red meat intake - FFQ Alistipes shahii 1.02% 0.78 Eubacterium hallii -0.4070 0.1363 3.2E-03 199 0.1583 0.0733 3.1E-02 726 2.3E-02 Red meat intake - FFQ Alistipes shahii 1.02% 0.78 Fish intake - DDR -0.4011 0.1435 5.7E-03 199 0.1580 0.0746 3.4E-02 726 2.9E-02 Red meat intake - FFQ Alistipes shahii 1.02% 0.78 Fish intake - FFQ -0.3852 0.1426 7.6E-03 199 0.1539 0.0736 3.7E-02 726 3.2E-02 Red meat intake - FFQ Alistipes shahii 1.02% 0.78 Plasma choline -0.3875 0.1420 7.0E-03 199 0.1543 0.0736 3.6E-02 726 3.4E-02 Red meat intake - FFQ Alistipes shahii 1.02% 0.78 Plasma L-carnitine -0.3816 0.1440 8.8E-03 199 0.1515 0.0732 3.9E-02 726 3.3E-02 Red meat intake - FFQ Alistipes shahii 1.02% 0.78 Red meat intake - DDR -0.4088 0.1735 2.0E-02 199 0.0771 0.0787 3.3E-01 726 2.4E-02 Red meat intake - FFQ Alistipes shahii 1.02% 0.78 Clostridiales bacterium 1 7 47FAA -0.4289 0.1429 3.1E-03 199 0.1549 0.0731 3.4E-02 726 2.7E-02 Red meat intake - FFQ Alistipes shahii 1.02% 0.78 Clostridium citroniae -0.3680 0.1424 1.1E-02 199 0.1805 0.0730 1.4E-02 726 4.3E-02 Red meat intake - FFQ Alistipes shahii 1.02% 0.78 Clostridium clostridioforme -0.3900 0.1424 6.8E-03 199 0.1533 0.0725 3.5E-02 726 4.9E-02 Red meat intake - FFQ Alistipes shahii 1.02% 0.78 Clostridium nexile -0.3785 0.1425 8.6E-03 199 0.1487 0.0735 4.3E-02 726 3.1E-02 Red meat intake - FFQ Alistipes shahii 1.02% 0.78 Eggerthella (unclassified) -0.3640 0.1416 1.1E-02 199 0.1619 0.0735 2.8E-02 726 3.7E-02 Red meat intake - FFQ Alistipes shahii 1.02% 0.78 Erysipelotrichaceae bacterium 21 3 -0.3668 0.1421 1.1E-02 199 0.1538 0.0736 3.7E-02 726 3.9E-02 Red meat intake - FFQ Alistipes shahii 1.02% 0.78 Roseburia hominis -0.3794 0.1447 9.5E-03 199 0.1477 0.0725 4.2E-02 726 4.6E-02 Red meat intake - DDR Alistipes shahii 1.02% 0.78 Fully adjusted -0.0359 0.0412 3.8E-01 199 0.0642 0.0204 1.7E-03 726 1.4E-01 Red meat intake - DDR Alistipes shahii 1.02% 0.78 Choline intake - DDR -0.0470 0.0437 2.8E-01 199 0.0510 0.0216 1.8E-02 726 1.3E-01 Red meat intake - DDR Alistipes shahii 1.02% 0.78 Choline intake - FFQ -0.0371 0.0430 3.9E-01 199 0.0597 0.0211 4.8E-03 726 2.0E-01 Red meat intake - DDR Alistipes shahii 1.02% 0.78 Dairy intake - DDR -0.0350 0.0404 3.9E-01 199 0.0649 0.0204 1.5E-03 726 1.4E-01 Red meat intake - DDR Alistipes shahii 1.02% 0.78 Dairy intake - FFQ -0.0256 0.0416 5.4E-01 199 0.0653 0.0204 1.4E-03 726 1.7E-01 Red meat intake - DDR Alistipes shahii 1.02% 0.78 Egg intake - DDR -0.0382 0.0418 3.6E-01 199 0.0629 0.0204 2.2E-03 726 1.3E-01 Red meat intake - DDR Alistipes shahii 1.02% 0.78 Egg intake - FFQ -0.0363 0.0422 3.9E-01 199 0.0608 0.0204 3.0E-03 726 1.9E-01 Red meat intake - DDR Alistipes shahii 1.02% 0.78 Eubacterium biforme -0.0312 0.0412 4.5E-01 199 0.0641 0.0204 1.8E-03 726 1.4E-01 Red meat intake - DDR Alistipes shahii 1.02% 0.78 Eubacterium hallii -0.0429 0.0401 2.9E-01 199 0.0651 0.0203 1.4E-03 726 1.0E-01 Red meat intake - DDR Alistipes shahii 1.02% 0.78 Fish intake - DDR -0.0306 0.0411 4.6E-01 199 0.0641 0.0204 1.7E-03 726 1.3E-01 Red meat intake - DDR Alistipes shahii 1.02% 0.78 Fish intake - FFQ -0.0300 0.0424 4.8E-01 199 0.0667 0.0203 1.1E-03 726 1.2E-01 Red meat intake - DDR Alistipes shahii 1.02% 0.78 Plasma choline -0.0375 0.0408 3.6E-01 199 0.0641 0.0204 1.7E-03 726 1.4E-01 Red meat intake - DDR Alistipes shahii 1.02% 0.78 Plasma L-carnitine -0.0357 0.0424 4.0E-01 199 0.0595 0.0204 3.6E-03 726 1.3E-01 Red meat intake - DDR Alistipes shahii 1.02% 0.78 Red meat intake - FFQ 0.0268 0.0475 5.7E-01 199 0.0565 0.0216 9.0E-03 726 1.9E-01 Red meat intake - DDR Alistipes shahii 1.02% 0.78 Clostridiales bacterium 1 7 47FAA -0.0403 0.0411 3.3E-01 199 0.0622 0.0202 2.2E-03 726 1.4E-01 Red meat intake - DDR Alistipes shahii 1.02% 0.78 Clostridium citroniae -0.0354 0.0410 3.9E-01 199 0.0623 0.0202 2.1E-03 726 1.8E-01 Red meat intake - DDR Alistipes shahii 1.02% 0.78 Clostridium clostridioforme -0.0372 0.0413 3.7E-01 199 0.0672 0.0200 8.4E-04 726 1.6E-01 Red meat intake - DDR Alistipes shahii 1.02% 0.78 Clostridium nexile -0.0351 0.0412 4.0E-01 199 0.0623 0.0204 2.3E-03 726 1.4E-01 Red meat intake - DDR Alistipes shahii 1.02% 0.78 Eggerthella (unclassified) -0.0321 0.0411 4.4E-01 199 0.0716 0.0205 5.2E-04 726 1.4E-01 Red meat intake - DDR Alistipes shahii 1.02% 0.78 Erysipelotrichaceae bacterium 21 3 -0.0397 0.0409 3.3E-01 199 0.0646 0.0204 1.6E-03 726 1.4E-01 Red meat intake - DDR Alistipes shahii 1.02% 0.78 Roseburia hominis -0.0361 0.0413 3.8E-01 199 0.0678 0.0200 7.6E-04 726 1.1E-01 Choline intake - FFQ Alistipes shahii 1.02% 0.78 Fully adjusted 0.1270 0.0993 2.0E-01 199 0.1459 0.0622 1.9E-02 726 3.4E-02 Choline intake - FFQ Alistipes shahii 1.02% 0.78 Choline intake - DDR 0.1838 0.1134 1.1E-01 199 0.0961 0.0666 1.5E-01 726 2.4E-02 Choline intake - FFQ Alistipes shahii 1.02% 0.78 Dairy intake - DDR 0.0708 0.1037 5.0E-01 199 0.1467 0.0626 1.9E-02 726 3.1E-02 Choline intake - FFQ Alistipes shahii 1.02% 0.78 Dairy intake - FFQ 0.0282 0.1093 8.0E-01 199 0.1357 0.0641 3.5E-02 726 3.1E-02 Choline intake - FFQ Alistipes shahii 1.02% 0.78 Egg intake - DDR 0.1365 0.1032 1.9E-01 199 0.1394 0.0651 3.3E-02 726 3.4E-02 Choline intake - FFQ Alistipes shahii 1.02% 0.78 Egg intake - FFQ 0.0637 0.1142 5.8E-01 199 0.0994 0.0730 1.7E-01 726 3.2E-02 Choline intake - FFQ Alistipes shahii 1.02% 0.78 Eubacterium biforme 0.1150 0.0988 2.5E-01 199 0.1465 0.0623 1.9E-02 726 3.4E-02 Choline intake - FFQ Alistipes shahii 1.02% 0.78 Eubacterium hallii 0.1260 0.0947 1.8E-01 199 0.1360 0.0621 2.9E-02 726 5.0E-02 Choline intake - FFQ Alistipes shahii 1.02% 0.78 Fish intake - DDR 0.1206 0.0987 2.2E-01 199 0.1699 0.0615 5.9E-03 726 1.7E-02 Choline intake - FFQ Alistipes shahii 1.02% 0.78 Fish intake - FFQ 0.1280 0.0992 2.0E-01 199 0.1451 0.0623 2.0E-02 726 4.0E-02 Choline intake - FFQ Alistipes shahii 1.02% 0.78 Plasma choline 0.1010 0.1005 3.2E-01 199 0.1450 0.0623 2.0E-02 726 3.1E-02 Choline intake - FFQ Alistipes shahii 1.02% 0.78 Plasma L-carnitine 0.1396 0.1012 1.7E-01 199 0.1264 0.0625 4.4E-02 726 3.0E-02 Choline intake - FFQ Alistipes shahii 1.02% 0.78 Red meat intake - DDR 0.1691 0.1035 1.0E-01 199 0.1193 0.0629 5.8E-02 726 3.0E-02 Choline intake - FFQ Alistipes shahii 1.02% 0.78 Red meat intake - FFQ 0.1981 0.0997 4.9E-02 199 0.1078 0.0649 9.7E-02 726 4.4E-02 Choline intake - FFQ Alistipes shahii 1.02% 0.78 Clostridiales bacterium 1 7 47FAA 0.1263 0.0993 2.1E-01 199 0.1524 0.0618 1.4E-02 726 4.8E-02 Choline intake - FFQ Alistipes shahii 1.02% 0.78 Clostridium citroniae 0.1249 0.0987 2.1E-01 199 0.1473 0.0616 1.7E-02 726 4.0E-02 Choline intake - FFQ Alistipes shahii 1.02% 0.78 Clostridium clostridioforme 0.1224 0.0993 2.2E-01 199 0.1458 0.0613 1.8E-02 726 4.7E-02 Choline intake - FFQ Alistipes shahii 1.02% 0.78 Clostridium nexile 0.1145 0.1000 2.5E-01 199 0.1333 0.0624 3.3E-02 726 3.1E-02 Choline intake - FFQ Alistipes shahii 1.02% 0.78 Eggerthella (unclassified) 0.1018 0.0993 3.1E-01 199 0.1507 0.0621 1.6E-02 726 1.6E-02 Choline intake - FFQ Alistipes shahii 1.02% 0.78 Erysipelotrichaceae bacterium 21 3 0.1334 0.0985 1.8E-01 199 0.1432 0.0625 2.2E-02 726 3.8E-02 Choline intake - FFQ Alistipes shahii 1.02% 0.78 Roseburia hominis 0.1293 0.0995 2.0E-01 199 0.1446 0.0613 1.9E-02 726 2.4E-02 Choline intake - DDR Alistipes shahii 1.02% 0.78 Fully adjusted 0.0337 0.0880 7.0E-01 199 0.1273 0.0458 5.6E-03 726 9.1E-02 Choline intake - DDR Alistipes shahii 1.02% 0.78 Choline intake - FFQ -0.0148 0.0983 8.8E-01 199 0.1024 0.0495 3.9E-02 726 6.5E-02 Choline intake - DDR Alistipes shahii 1.02% 0.78 Dairy intake - DDR -0.0266 0.0886 7.6E-01 199 0.1271 0.0459 5.8E-03 726 7.8E-02 Choline intake - DDR Alistipes shahii 1.02% 0.78 Dairy intake - FFQ -0.0408 0.0902 6.5E-01 199 0.1229 0.0463 8.2E-03 726 6.2E-02 Choline intake - DDR Alistipes shahii 1.02% 0.78 Egg intake - DDR 0.0455 0.1161 7.0E-01 199 0.1674 0.0609 6.2E-03 726 1.1E-01 Choline intake - DDR Alistipes shahii 1.02% 0.78 Egg intake - FFQ -0.0044 0.0933 9.6E-01 199 0.1107 0.0480 2.1E-02 726 6.3E-02 Choline intake - DDR Alistipes shahii 1.02% 0.78 Eubacterium biforme 0.0270 0.0877 7.6E-01 199 0.1278 0.0459 5.5E-03 726 9.4E-02 Choline intake - DDR Alistipes shahii 1.02% 0.78 Eubacterium hallii 0.0570 0.0858 5.1E-01 199 0.1204 0.0458 8.8E-03 726 1.8E-01 Choline intake - DDR Alistipes shahii 1.02% 0.78 Fish intake - DDR 0.0438 0.0876 6.2E-01 199 0.1317 0.0463 4.5E-03 726 7.4E-02 Choline intake - DDR Alistipes shahii 1.02% 0.78 Fish intake - FFQ 0.0320 0.0884 7.2E-01 199 0.1268 0.0457 5.7E-03 726 7.5E-02 Choline intake - DDR Alistipes shahii 1.02% 0.78 Plasma choline 0.0349 0.0871 6.9E-01 199 0.1254 0.0460 6.6E-03 726 1.0E-01 Choline intake - DDR Alistipes shahii 1.02% 0.78 Plasma L-carnitine 0.0373 0.0894 6.8E-01 199 0.1205 0.0458 8.7E-03 726 6.6E-02 Choline intake - DDR Alistipes shahii 1.02% 0.78 Red meat intake - DDR 0.0718 0.0941 4.5E-01 199 0.0878 0.0486 7.1E-02 726 1.2E-01 21

Supplementary Data 2a Absence (species)/ Non- Presence (species)/ Stratified by Dietary Exposure Additionally conditioned on producer (mixed score) TMAO-producer (mixed P-interaction Taxa Abundance Prevalence Effect Se P n Effect Se P n Choline intake - DDR Alistipes shahii 1.02% 0.78 Red meat intake - FFQ 0.0768 0.0883 3.9E-01 199 0.1179 0.0462 1.1E-02 726 7.3E-02 Choline intake - DDR Alistipes shahii 1.02% 0.78 Clostridiales bacterium 1 7 47FAA 0.0230 0.0880 7.9E-01 199 0.1272 0.0455 5.3E-03 726 8.2E-02 Choline intake - DDR Alistipes shahii 1.02% 0.78 Clostridium citroniae 0.0368 0.0876 6.8E-01 199 0.1209 0.0454 8.0E-03 726 1.2E-01 Choline intake - DDR Alistipes shahii 1.02% 0.78 Clostridium clostridioforme 0.0318 0.0881 7.2E-01 199 0.1249 0.0452 5.8E-03 726 7.8E-02 Choline intake - DDR Alistipes shahii 1.02% 0.78 Clostridium nexile 0.0367 0.0879 6.8E-01 199 0.1205 0.0459 8.9E-03 726 1.1E-01 Choline intake - DDR Alistipes shahii 1.02% 0.78 Eggerthella (unclassified) 0.0112 0.0885 9.0E-01 199 0.1347 0.0459 3.4E-03 726 6.3E-02 Choline intake - DDR Alistipes shahii 1.02% 0.78 Erysipelotrichaceae bacterium 21 3 0.0270 0.0873 7.6E-01 199 0.1272 0.0459 5.7E-03 726 8.9E-02 Choline intake - DDR Alistipes shahii 1.02% 0.78 Roseburia hominis 0.0326 0.0883 7.1E-01 199 0.1410 0.0452 1.9E-03 726 6.3E-02 Plasma choline Alistipes shahii 1.02% 0.78 Fully adjusted 0.0996 0.0661 1.3E-01 199 0.0381 0.0389 3.3E-01 726 9.0E-01 Plasma choline Alistipes shahii 1.02% 0.78 Choline intake - DDR 0.1004 0.0663 1.3E-01 199 0.0283 0.0389 4.7E-01 726 8.1E-01 Plasma choline Alistipes shahii 1.02% 0.78 Choline intake - FFQ 0.0986 0.0671 1.4E-01 199 0.0356 0.0395 3.7E-01 726 8.5E-01 Plasma choline Alistipes shahii 1.02% 0.78 Dairy intake - DDR 0.0847 0.0662 2.0E-01 199 0.0377 0.0390 3.3E-01 726 9.2E-01 Plasma choline Alistipes shahii 1.02% 0.78 Dairy intake - FFQ 0.0749 0.0662 2.6E-01 199 0.0397 0.0389 3.1E-01 726 9.6E-01 Plasma choline Alistipes shahii 1.02% 0.78 Egg intake - DDR 0.0996 0.0663 1.3E-01 199 0.0349 0.0391 3.7E-01 726 8.7E-01 Plasma choline Alistipes shahii 1.02% 0.78 Egg intake - FFQ 0.0882 0.0664 1.9E-01 199 0.0341 0.0389 3.8E-01 726 9.3E-01 Plasma choline Alistipes shahii 1.02% 0.78 Eubacterium biforme 0.0957 0.0655 1.5E-01 199 0.0386 0.0390 3.2E-01 726 9.0E-01 Plasma choline Alistipes shahii 1.02% 0.78 Eubacterium hallii 0.0843 0.0637 1.9E-01 199 0.0377 0.0388 3.3E-01 726 9.2E-01 Plasma choline Alistipes shahii 1.02% 0.78 Fish intake - DDR 0.1126 0.0614 6.8E-02 199 0.0311 0.0390 4.3E-01 726 7.1E-01 Plasma choline Alistipes shahii 1.02% 0.78 Fish intake - FFQ 0.1015 0.0666 1.3E-01 199 0.0354 0.0389 3.6E-01 726 8.3E-01 Plasma choline Alistipes shahii 1.02% 0.78 Plasma L-carnitine 0.1295 0.0710 7.0E-02 199 0.0150 0.0397 7.1E-01 726 9.3E-01 Plasma choline Alistipes shahii 1.02% 0.78 Red meat intake - DDR 0.1009 0.0667 1.3E-01 199 0.0338 0.0387 3.8E-01 726 9.4E-01 Plasma choline Alistipes shahii 1.02% 0.78 Red meat intake - FFQ 0.1017 0.0650 1.2E-01 199 0.0414 0.0390 2.9E-01 726 9.3E-01 Plasma choline Alistipes shahii 1.02% 0.78 Clostridiales bacterium 1 7 47FAA 0.0854 0.0668 2.0E-01 199 0.0462 0.0387 2.3E-01 726 8.7E-01 Plasma choline Alistipes shahii 1.02% 0.78 Clostridium citroniae 0.0805 0.0671 2.3E-01 199 0.0379 0.0385 3.3E-01 726 9.1E-01 Plasma choline Alistipes shahii 1.02% 0.78 Clostridium clostridioforme 0.1050 0.0662 1.1E-01 199 0.0566 0.0385 1.4E-01 726 8.9E-01 Plasma choline Alistipes shahii 1.02% 0.78 Clostridium nexile 0.1265 0.0677 6.3E-02 199 0.0405 0.0388 3.0E-01 726 7.3E-01 Plasma choline Alistipes shahii 1.02% 0.78 Eggerthella (unclassified) 0.1088 0.0654 9.8E-02 199 0.0351 0.0389 3.7E-01 726 8.4E-01 Plasma choline Alistipes shahii 1.02% 0.78 Erysipelotrichaceae bacterium 21 3 0.1150 0.0659 8.3E-02 199 0.0396 0.0390 3.1E-01 726 8.8E-01 Plasma choline Alistipes shahii 1.02% 0.78 Roseburia hominis 0.1003 0.0662 1.3E-01 199 0.0519 0.0384 1.8E-01 726 9.6E-01 Plasma L-carnitine Alistipes shahii 1.02% 0.78 Fully adjusted -0.0351 0.0691 6.1E-01 199 0.1020 0.0358 4.5E-03 726 4.3E-02 Plasma L-carnitine Alistipes shahii 1.02% 0.78 Choline intake - DDR -0.0320 0.0711 6.5E-01 199 0.0962 0.0357 7.2E-03 726 3.0E-02 Plasma L-carnitine Alistipes shahii 1.02% 0.78 Choline intake - FFQ -0.0480 0.0706 5.0E-01 199 0.0927 0.0368 1.2E-02 726 5.5E-02 Plasma L-carnitine Alistipes shahii 1.02% 0.78 Dairy intake - DDR -0.0682 0.0701 3.3E-01 199 0.1022 0.0361 4.8E-03 726 4.0E-02 Plasma L-carnitine Alistipes shahii 1.02% 0.78 Dairy intake - FFQ -0.0553 0.0685 4.2E-01 199 0.0995 0.0359 5.7E-03 726 3.7E-02 Plasma L-carnitine Alistipes shahii 1.02% 0.78 Egg intake - DDR -0.0369 0.0697 6.0E-01 199 0.1010 0.0358 5.0E-03 726 4.2E-02 Plasma L-carnitine Alistipes shahii 1.02% 0.78 Egg intake - FFQ -0.0549 0.0698 4.3E-01 199 0.0970 0.0358 7.0E-03 726 3.8E-02 Plasma L-carnitine Alistipes shahii 1.02% 0.78 Eubacterium biforme -0.0215 0.0688 7.5E-01 199 0.1019 0.0358 4.6E-03 726 4.5E-02 Plasma L-carnitine Alistipes shahii 1.02% 0.78 Eubacterium hallii -0.0066 0.0668 9.2E-01 199 0.0984 0.0357 6.0E-03 726 7.5E-02 Plasma L-carnitine Alistipes shahii 1.02% 0.78 Fish intake - DDR -0.0161 0.0657 8.1E-01 199 0.0985 0.0359 6.3E-03 726 6.1E-02 Plasma L-carnitine Alistipes shahii 1.02% 0.78 Fish intake - FFQ -0.0346 0.0690 6.2E-01 199 0.1000 0.0358 5.4E-03 726 5.0E-02 Plasma L-carnitine Alistipes shahii 1.02% 0.78 Plasma choline -0.0846 0.0739 2.5E-01 199 0.0990 0.0367 7.1E-03 726 3.5E-02 Plasma L-carnitine Alistipes shahii 1.02% 0.78 Red meat intake - DDR -0.0192 0.0713 7.9E-01 199 0.0927 0.0358 9.9E-03 726 2.6E-02 Plasma L-carnitine Alistipes shahii 1.02% 0.78 Red meat intake - FFQ -0.0129 0.0685 8.5E-01 199 0.1010 0.0358 4.9E-03 726 4.2E-02 Plasma L-carnitine Alistipes shahii 1.02% 0.78 Clostridiales bacterium 1 7 47FAA -0.0324 0.0689 6.4E-01 199 0.0998 0.0356 5.1E-03 726 4.7E-02 Plasma L-carnitine Alistipes shahii 1.02% 0.78 Clostridium citroniae -0.0338 0.0688 6.2E-01 199 0.1026 0.0354 3.9E-03 726 3.9E-02 Plasma L-carnitine Alistipes shahii 1.02% 0.78 Clostridium clostridioforme -0.0321 0.0692 6.4E-01 199 0.0993 0.0353 5.1E-03 726 4.2E-02 Plasma L-carnitine Alistipes shahii 1.02% 0.78 Clostridium nexile -0.0310 0.0691 6.5E-01 199 0.1092 0.0358 2.4E-03 726 3.7E-02 Plasma L-carnitine Alistipes shahii 1.02% 0.78 Eggerthella (unclassified) -0.0241 0.0686 7.3E-01 199 0.1055 0.0358 3.3E-03 726 4.9E-02 Plasma L-carnitine Alistipes shahii 1.02% 0.78 Erysipelotrichaceae bacterium 21 3 -0.0416 0.0687 5.5E-01 199 0.1041 0.0359 3.9E-03 726 4.1E-02 Plasma L-carnitine Alistipes shahii 1.02% 0.78 Roseburia hominis -0.0301 0.0698 6.7E-01 199 0.1170 0.0353 9.7E-04 726 4.2E-02 Dairy intake - FFQ Alistipes shahii 1.02% 0.78 Fully adjusted 0.1219 0.0481 1.2E-02 199 0.0396 0.0304 1.9E-01 726 4.1E-01 Dairy intake - FFQ Alistipes shahii 1.02% 0.78 Choline intake - DDR 0.1338 0.0496 7.7E-03 199 0.0251 0.0307 4.1E-01 726 4.7E-01 Dairy intake - FFQ Alistipes shahii 1.02% 0.78 Choline intake - FFQ 0.1125 0.0542 3.9E-02 199 0.0219 0.0324 5.0E-01 726 5.4E-01 Dairy intake - FFQ Alistipes shahii 1.02% 0.78 Dairy intake - DDR 0.1026 0.0637 1.1E-01 199 0.0475 0.0355 1.8E-01 726 4.0E-01 Dairy intake - FFQ Alistipes shahii 1.02% 0.78 Egg intake - DDR 0.1225 0.0482 1.2E-02 199 0.0394 0.0304 2.0E-01 726 4.2E-01 Dairy intake - FFQ Alistipes shahii 1.02% 0.78 Egg intake - FFQ 0.1166 0.0481 1.6E-02 199 0.0356 0.0304 2.4E-01 726 4.4E-01 Dairy intake - FFQ Alistipes shahii 1.02% 0.78 Eubacterium biforme 0.1137 0.0479 1.9E-02 199 0.0401 0.0305 1.9E-01 726 4.2E-01 Dairy intake - FFQ Alistipes shahii 1.02% 0.78 Eubacterium hallii 0.1127 0.0463 1.6E-02 199 0.0421 0.0303 1.7E-01 726 4.8E-01 Dairy intake - FFQ Alistipes shahii 1.02% 0.78 Fish intake - DDR 0.1255 0.0482 1.0E-02 199 0.0323 0.0305 2.9E-01 726 3.9E-01 Dairy intake - FFQ Alistipes shahii 1.02% 0.78 Fish intake - FFQ 0.1218 0.0481 1.2E-02 199 0.0418 0.0305 1.7E-01 726 4.4E-01 Dairy intake - FFQ Alistipes shahii 1.02% 0.78 Plasma choline 0.1131 0.0487 2.1E-02 199 0.0406 0.0304 1.8E-01 726 4.5E-01 Dairy intake - FFQ Alistipes shahii 1.02% 0.78 Plasma L-carnitine 0.1263 0.0484 9.9E-03 199 0.0344 0.0303 2.6E-01 726 4.1E-01 Dairy intake - FFQ Alistipes shahii 1.02% 0.78 Red meat intake - DDR 0.1198 0.0483 1.4E-02 199 0.0411 0.0302 1.7E-01 726 4.3E-01 Dairy intake - FFQ Alistipes shahii 1.02% 0.78 Red meat intake - FFQ 0.1124 0.0475 1.9E-02 199 0.0494 0.0307 1.1E-01 726 4.5E-01 Dairy intake - FFQ Alistipes shahii 1.02% 0.78 Clostridiales bacterium 1 7 47FAA 0.1200 0.0479 1.3E-02 199 0.0433 0.0302 1.5E-01 726 4.0E-01 Dairy intake - FFQ Alistipes shahii 1.02% 0.78 Clostridium citroniae 0.1313 0.0479 6.7E-03 199 0.0401 0.0301 1.8E-01 726 3.1E-01 Dairy intake - FFQ Alistipes shahii 1.02% 0.78 Clostridium clostridioforme 0.1305 0.0483 7.6E-03 199 0.0307 0.0300 3.1E-01 726 3.8E-01 Dairy intake - FFQ Alistipes shahii 1.02% 0.78 Clostridium nexile 0.1175 0.0482 1.6E-02 199 0.0358 0.0304 2.4E-01 726 4.3E-01 Dairy intake - FFQ Alistipes shahii 1.02% 0.78 Eggerthella (unclassified) 0.1030 0.0491 3.7E-02 199 0.0397 0.0303 1.9E-01 726 5.6E-01 Dairy intake - FFQ Alistipes shahii 1.02% 0.78 Erysipelotrichaceae bacterium 21 3 0.1173 0.0479 1.5E-02 199 0.0385 0.0305 2.1E-01 726 4.0E-01 Dairy intake - FFQ Alistipes shahii 1.02% 0.78 Roseburia hominis 0.1269 0.0484 9.5E-03 199 0.0435 0.0299 1.5E-01 726 3.8E-01 Dairy intake - DDR Alistipes shahii 1.02% 0.78 Fully adjusted 0.1316 0.0447 3.7E-03 199 0.0116 0.0309 7.1E-01 726 1.4E-01 Dairy intake - DDR Alistipes shahii 1.02% 0.78 Choline intake - DDR 0.1348 0.0461 3.9E-03 199 0.0104 0.0308 7.4E-01 726 1.9E-01 Dairy intake - DDR Alistipes shahii 1.02% 0.78 Choline intake - FFQ 0.1415 0.0454 2.1E-03 199 0.0027 0.0319 9.3E-01 726 1.2E-01 Dairy intake - DDR Alistipes shahii 1.02% 0.78 Dairy intake - FFQ 0.1025 0.0570 7.4E-02 199 -0.0047 0.0349 8.9E-01 726 1.5E-01 Dairy intake - DDR Alistipes shahii 1.02% 0.78 Egg intake - DDR 0.1338 0.0450 3.4E-03 199 0.0148 0.0310 6.3E-01 726 1.4E-01 Dairy intake - DDR Alistipes shahii 1.02% 0.78 Egg intake - FFQ 0.1391 0.0448 2.2E-03 199 0.0129 0.0308 6.8E-01 726 1.5E-01 Dairy intake - DDR Alistipes shahii 1.02% 0.78 Eubacterium biforme 0.1275 0.0447 4.8E-03 199 0.0120 0.0309 7.0E-01 726 1.4E-01 Dairy intake - DDR Alistipes shahii 1.02% 0.78 Eubacterium hallii 0.1330 0.0434 2.5E-03 199 0.0114 0.0308 7.1E-01 726 9.3E-02 Dairy intake - DDR Alistipes shahii 1.02% 0.78 Fish intake - DDR 0.1322 0.0444 3.3E-03 199 0.0092 0.0310 7.7E-01 726 1.2E-01 22

Supplementary Data 2a Absence (species)/ Non- Presence (species)/ Stratified by Dietary Exposure Additionally conditioned on producer (mixed score) TMAO-producer (mixed P-interaction Taxa Abundance Prevalence Effect Se P n Effect Se P n Dairy intake - DDR Alistipes shahii 1.02% 0.78 Fish intake - FFQ 0.1393 0.0448 2.2E-03 199 0.0032 0.0310 9.2E-01 726 9.7E-02 Dairy intake - DDR Alistipes shahii 1.02% 0.78 Plasma choline 0.1251 0.0444 5.4E-03 199 0.0116 0.0309 7.1E-01 726 1.4E-01 Dairy intake - DDR Alistipes shahii 1.02% 0.78 Plasma L-carnitine 0.1381 0.0456 2.8E-03 199 0.0035 0.0309 9.1E-01 726 1.4E-01 Dairy intake - DDR Alistipes shahii 1.02% 0.78 Red meat intake - DDR 0.1308 0.0449 4.0E-03 199 0.0194 0.0309 5.3E-01 726 1.5E-01 Dairy intake - DDR Alistipes shahii 1.02% 0.78 Red meat intake - FFQ 0.1263 0.0446 5.2E-03 199 0.0163 0.0309 6.0E-01 726 1.5E-01 Dairy intake - DDR Alistipes shahii 1.02% 0.78 Clostridiales bacterium 1 7 47FAA 0.1339 0.0445 3.0E-03 199 0.0175 0.0307 5.7E-01 726 1.2E-01 Dairy intake - DDR Alistipes shahii 1.02% 0.78 Clostridium citroniae 0.1386 0.0445 2.2E-03 199 0.0195 0.0306 5.2E-01 726 1.1E-01 Dairy intake - DDR Alistipes shahii 1.02% 0.78 Clostridium clostridioforme 0.1503 0.0462 1.4E-03 199 0.0040 0.0305 8.9E-01 726 2.1E-01 Dairy intake - DDR Alistipes shahii 1.02% 0.78 Clostridium nexile 0.1285 0.0448 4.6E-03 199 0.0161 0.0309 6.0E-01 726 1.9E-01 Dairy intake - DDR Alistipes shahii 1.02% 0.78 Eggerthella (unclassified) 0.1257 0.0447 5.5E-03 199 0.0150 0.0309 6.3E-01 726 1.6E-01 Dairy intake - DDR Alistipes shahii 1.02% 0.78 Erysipelotrichaceae bacterium 21 3 0.1238 0.0446 6.1E-03 199 0.0106 0.0310 7.3E-01 726 1.4E-01 Dairy intake - DDR Alistipes shahii 1.02% 0.78 Roseburia hominis 0.1321 0.0448 3.6E-03 199 0.0190 0.0305 5.3E-01 726 1.5E-01 Egg intake - FFQ Alistipes shahii 1.02% 0.78 Fully adjusted 0.2593 0.1648 1.2E-01 199 0.1964 0.0939 3.7E-02 726 7.6E-01 Egg intake - FFQ Alistipes shahii 1.02% 0.78 Choline intake - DDR 0.3056 0.1738 8.0E-02 199 0.1355 0.0965 1.6E-01 726 7.1E-01 Egg intake - FFQ Alistipes shahii 1.02% 0.78 Choline intake - FFQ 0.2124 0.1895 2.6E-01 199 0.1395 0.1142 2.2E-01 726 6.9E-01 Egg intake - FFQ Alistipes shahii 1.02% 0.78 Dairy intake - DDR 0.2505 0.1636 1.3E-01 199 0.1965 0.0939 3.7E-02 726 7.5E-01 Egg intake - FFQ Alistipes shahii 1.02% 0.78 Dairy intake - FFQ 0.2277 0.1631 1.6E-01 199 0.1892 0.0940 4.5E-02 726 7.8E-01 Egg intake - FFQ Alistipes shahii 1.02% 0.78 Egg intake - DDR 0.3204 0.1897 9.3E-02 199 0.1878 0.1044 7.2E-02 726 7.7E-01 Egg intake - FFQ Alistipes shahii 1.02% 0.78 Eubacterium biforme 0.2421 0.1635 1.4E-01 199 0.1973 0.0940 3.6E-02 726 7.6E-01 Egg intake - FFQ Alistipes shahii 1.02% 0.78 Eubacterium hallii 0.2075 0.1591 1.9E-01 199 0.2027 0.0935 3.1E-02 726 6.8E-01 Egg intake - FFQ Alistipes shahii 1.02% 0.78 Fish intake - DDR 0.2473 0.1641 1.3E-01 199 0.1790 0.0942 5.8E-02 726 6.0E-01 Egg intake - FFQ Alistipes shahii 1.02% 0.78 Fish intake - FFQ 0.2589 0.1647 1.2E-01 199 0.1981 0.0940 3.6E-02 726 7.6E-01 Egg intake - FFQ Alistipes shahii 1.02% 0.78 Plasma choline 0.2325 0.1657 1.6E-01 199 0.1923 0.0940 4.1E-02 726 7.4E-01 Egg intake - FFQ Alistipes shahii 1.02% 0.78 Plasma L-carnitine 0.2815 0.1674 9.4E-02 199 0.1776 0.0937 5.8E-02 726 7.3E-01 Egg intake - FFQ Alistipes shahii 1.02% 0.78 Red meat intake - DDR 0.2803 0.1656 9.2E-02 199 0.1658 0.0939 7.8E-02 726 8.0E-01 Egg intake - FFQ Alistipes shahii 1.02% 0.78 Red meat intake - FFQ 0.2317 0.1625 1.6E-01 199 0.1786 0.0955 6.2E-02 726 7.6E-01 Egg intake - FFQ Alistipes shahii 1.02% 0.78 Clostridiales bacterium 1 7 47FAA 0.2366 0.1651 1.5E-01 199 0.1974 0.0932 3.4E-02 726 7.8E-01 Egg intake - FFQ Alistipes shahii 1.02% 0.78 Clostridium citroniae 0.2494 0.1640 1.3E-01 199 0.1742 0.0931 6.2E-02 726 8.4E-01 Egg intake - FFQ Alistipes shahii 1.02% 0.78 Clostridium clostridioforme 0.2643 0.1647 1.1E-01 199 0.2049 0.0925 2.7E-02 726 7.7E-01 Egg intake - FFQ Alistipes shahii 1.02% 0.78 Clostridium nexile 0.2483 0.1648 1.3E-01 199 0.1831 0.0939 5.2E-02 726 8.3E-01 Egg intake - FFQ Alistipes shahii 1.02% 0.78 Eggerthella (unclassified) 0.1876 0.1678 2.7E-01 199 0.2028 0.0937 3.1E-02 726 5.7E-01 Egg intake - FFQ Alistipes shahii 1.02% 0.78 Erysipelotrichaceae bacterium 21 3 0.2434 0.1639 1.4E-01 199 0.1928 0.0942 4.1E-02 726 7.8E-01 Egg intake - FFQ Alistipes shahii 1.02% 0.78 Roseburia hominis 0.2631 0.1651 1.1E-01 199 0.1969 0.0924 3.3E-02 726 7.4E-01 Egg intake - DDR Alistipes shahii 1.02% 0.78 Fully adjusted 0.0175 0.1335 9.0E-01 199 0.0801 0.0711 2.6E-01 726 3.9E-01 Egg intake - DDR Alistipes shahii 1.02% 0.78 Choline intake - DDR -0.0274 0.1762 8.8E-01 199 -0.0849 0.0928 3.6E-01 726 4.1E-01 Egg intake - DDR Alistipes shahii 1.02% 0.78 Choline intake - FFQ -0.0561 0.1417 6.9E-01 199 0.0330 0.0760 6.6E-01 726 2.6E-01 Egg intake - DDR Alistipes shahii 1.02% 0.78 Dairy intake - DDR 0.0604 0.1315 6.5E-01 199 0.0830 0.0714 2.5E-01 726 4.3E-01 Egg intake - DDR Alistipes shahii 1.02% 0.78 Dairy intake - FFQ -0.0010 0.1315 9.9E-01 199 0.0772 0.0711 2.8E-01 726 3.5E-01 Egg intake - DDR Alistipes shahii 1.02% 0.78 Egg intake - FFQ -0.1054 0.1550 5.0E-01 199 0.0244 0.0791 7.6E-01 726 2.9E-01 Egg intake - DDR Alistipes shahii 1.02% 0.78 Eubacterium biforme 0.0053 0.1332 9.7E-01 199 0.0810 0.0711 2.6E-01 726 3.9E-01 Egg intake - DDR Alistipes shahii 1.02% 0.78 Eubacterium hallii 0.0418 0.1301 7.5E-01 199 0.0818 0.0708 2.5E-01 726 4.6E-01 Egg intake - DDR Alistipes shahii 1.02% 0.78 Fish intake - DDR 0.0179 0.1327 8.9E-01 199 0.0862 0.0714 2.3E-01 726 3.7E-01 Egg intake - DDR Alistipes shahii 1.02% 0.78 Fish intake - FFQ -0.0075 0.1342 9.6E-01 199 0.0692 0.0710 3.3E-01 726 3.8E-01 Egg intake - DDR Alistipes shahii 1.02% 0.78 Plasma choline 0.0144 0.1322 9.1E-01 199 0.0764 0.0713 2.8E-01 726 4.3E-01 Egg intake - DDR Alistipes shahii 1.02% 0.78 Plasma L-carnitine 0.0196 0.1343 8.8E-01 199 0.0782 0.0708 2.7E-01 726 3.6E-01 Egg intake - DDR Alistipes shahii 1.02% 0.78 Red meat intake - DDR 0.0522 0.1401 7.1E-01 199 0.0680 0.0708 3.4E-01 726 4.7E-01 Egg intake - DDR Alistipes shahii 1.02% 0.78 Red meat intake - FFQ 0.1121 0.1373 4.2E-01 199 0.0702 0.0713 3.3E-01 726 3.1E-01 Egg intake - DDR Alistipes shahii 1.02% 0.78 Clostridiales bacterium 1 7 47FAA 0.0127 0.1331 9.2E-01 199 0.0842 0.0705 2.3E-01 726 4.1E-01 Egg intake - DDR Alistipes shahii 1.02% 0.78 Clostridium citroniae 0.0275 0.1330 8.4E-01 199 0.0803 0.0703 2.5E-01 726 4.3E-01 Egg intake - DDR Alistipes shahii 1.02% 0.78 Clostridium clostridioforme 0.0096 0.1343 9.4E-01 199 0.0810 0.0700 2.5E-01 726 4.2E-01 Egg intake - DDR Alistipes shahii 1.02% 0.78 Clostridium nexile 0.0317 0.1338 8.1E-01 199 0.0664 0.0713 3.5E-01 726 5.4E-01 Egg intake - DDR Alistipes shahii 1.02% 0.78 Eggerthella (unclassified) -0.0177 0.1343 9.0E-01 199 0.0914 0.0711 2.0E-01 726 3.0E-01 Egg intake - DDR Alistipes shahii 1.02% 0.78 Erysipelotrichaceae bacterium 21 3 0.0050 0.1325 9.7E-01 199 0.0803 0.0711 2.6E-01 726 3.8E-01 Egg intake - DDR Alistipes shahii 1.02% 0.78 Roseburia hominis 0.0155 0.1341 9.1E-01 199 0.0983 0.0701 1.6E-01 726 2.8E-01 Fish intake - FFQ Alistipes shahii 1.02% 0.78 Fully adjusted 0.0548 0.3657 8.8E-01 199 0.4248 0.1427 3.0E-03 726 8.9E-02 Fish intake - FFQ Alistipes shahii 1.02% 0.78 Choline intake - DDR 0.0621 0.3674 8.7E-01 199 0.4327 0.1420 2.4E-03 726 7.3E-02 Fish intake - FFQ Alistipes shahii 1.02% 0.78 Choline intake - FFQ -0.0656 0.3755 8.6E-01 199 0.4091 0.1525 7.5E-03 726 4.5E-02 Fish intake - FFQ Alistipes shahii 1.02% 0.78 Dairy intake - DDR 0.1606 0.3665 6.6E-01 199 0.4235 0.1429 3.1E-03 726 1.1E-01 Fish intake - FFQ Alistipes shahii 1.02% 0.78 Dairy intake - FFQ 0.1298 0.3615 7.2E-01 199 0.4413 0.1432 2.1E-03 726 9.6E-02 Fish intake - FFQ Alistipes shahii 1.02% 0.78 Egg intake - DDR 0.0583 0.3671 8.7E-01 199 0.4212 0.1429 3.3E-03 726 9.3E-02 Fish intake - FFQ Alistipes shahii 1.02% 0.78 Egg intake - FFQ 0.1221 0.3667 7.4E-01 199 0.4440 0.1427 1.9E-03 726 1.1E-01 Fish intake - FFQ Alistipes shahii 1.02% 0.78 Eubacterium biforme 0.0431 0.3622 9.1E-01 199 0.4234 0.1432 3.2E-03 726 9.1E-02 Fish intake - FFQ Alistipes shahii 1.02% 0.78 Eubacterium hallii -0.1563 0.3548 6.6E-01 199 0.4171 0.1422 3.5E-03 726 5.4E-02 Fish intake - FFQ Alistipes shahii 1.02% 0.78 Fish intake - DDR -0.0213 0.3975 9.6E-01 199 0.3922 0.1482 8.3E-03 726 6.9E-02 Fish intake - FFQ Alistipes shahii 1.02% 0.78 Plasma choline 0.1383 0.3685 7.1E-01 199 0.4366 0.1433 2.4E-03 726 1.0E-01 Fish intake - FFQ Alistipes shahii 1.02% 0.78 Plasma L-carnitine 0.0699 0.3677 8.5E-01 199 0.4518 0.1424 1.6E-03 726 6.2E-02 Fish intake - FFQ Alistipes shahii 1.02% 0.78 Red meat intake - DDR 0.0902 0.3687 8.1E-01 199 0.4593 0.1421 1.3E-03 726 6.4E-02 Fish intake - FFQ Alistipes shahii 1.02% 0.78 Red meat intake - FFQ 0.1325 0.3606 7.1E-01 199 0.4575 0.1433 1.5E-03 726 8.5E-02 Fish intake - FFQ Alistipes shahii 1.02% 0.78 Clostridiales bacterium 1 7 47FAA 0.0112 0.3653 9.8E-01 199 0.4221 0.1417 3.0E-03 726 6.7E-02 Fish intake - FFQ Alistipes shahii 1.02% 0.78 Clostridium citroniae 0.0445 0.3637 9.0E-01 199 0.4025 0.1414 4.5E-03 726 7.8E-02 Fish intake - FFQ Alistipes shahii 1.02% 0.78 Clostridium clostridioforme 0.0840 0.3663 8.2E-01 199 0.4313 0.1406 2.2E-03 726 7.6E-02 Fish intake - FFQ Alistipes shahii 1.02% 0.78 Clostridium nexile 0.0778 0.3655 8.3E-01 199 0.4396 0.1425 2.1E-03 726 8.5E-02 Fish intake - FFQ Alistipes shahii 1.02% 0.78 Eggerthella (unclassified) 0.0952 0.3623 7.9E-01 199 0.4372 0.1426 2.2E-03 726 8.3E-02 Fish intake - FFQ Alistipes shahii 1.02% 0.78 Erysipelotrichaceae bacterium 21 3 0.0881 0.3635 8.1E-01 199 0.4296 0.1430 2.8E-03 726 8.8E-02 Fish intake - FFQ Alistipes shahii 1.02% 0.78 Roseburia hominis 0.0583 0.3663 8.7E-01 199 0.4473 0.1406 1.5E-03 726 8.2E-02 Fish intake - DDR Alistipes shahii 1.02% 0.78 Fully adjusted 0.0428 0.0486 3.8E-01 199 0.0476 0.0276 8.5E-02 726 7.9E-01 Fish intake - DDR Alistipes shahii 1.02% 0.78 Choline intake - DDR 0.0329 0.0519 5.3E-01 199 0.0294 0.0281 3.0E-01 726 7.0E-01 Fish intake - DDR Alistipes shahii 1.02% 0.78 Choline intake - FFQ 0.0523 0.0494 2.9E-01 199 0.0533 0.0282 6.0E-02 726 8.7E-01 Fish intake - DDR Alistipes shahii 1.02% 0.78 Dairy intake - DDR 0.0639 0.0483 1.9E-01 199 0.0482 0.0277 8.2E-02 726 8.3E-01 Fish intake - DDR Alistipes shahii 1.02% 0.78 Dairy intake - FFQ 0.0642 0.0488 1.9E-01 199 0.0486 0.0276 7.8E-02 726 8.5E-01 23

Supplementary Data 2a Absence (species)/ Non- Presence (species)/ Stratified by Dietary Exposure Additionally conditioned on producer (mixed score) TMAO-producer (mixed P-interaction Taxa Abundance Prevalence Effect Se P n Effect Se P n Fish intake - DDR Alistipes shahii 1.02% 0.78 Egg intake - DDR 0.0422 0.0489 3.9E-01 199 0.0492 0.0276 7.5E-02 726 7.6E-01 Fish intake - DDR Alistipes shahii 1.02% 0.78 Egg intake - FFQ 0.0401 0.0490 4.1E-01 199 0.0505 0.0275 6.7E-02 726 7.2E-01 Fish intake - DDR Alistipes shahii 1.02% 0.78 Eubacterium biforme 0.0468 0.0485 3.4E-01 199 0.0473 0.0276 8.7E-02 726 8.0E-01 Fish intake - DDR Alistipes shahii 1.02% 0.78 Eubacterium hallii 0.0227 0.0476 6.3E-01 199 0.0449 0.0275 1.0E-01 726 7.1E-01 Fish intake - DDR Alistipes shahii 1.02% 0.78 Fish intake - FFQ 0.0592 0.0535 2.7E-01 199 0.0282 0.0285 3.2E-01 726 7.5E-01 Fish intake - DDR Alistipes shahii 1.02% 0.78 Plasma choline 0.0457 0.0482 3.4E-01 199 0.0498 0.0277 7.3E-02 726 7.7E-01 Fish intake - DDR Alistipes shahii 1.02% 0.78 Plasma L-carnitine 0.0436 0.0497 3.8E-01 199 0.0532 0.0275 5.3E-02 726 6.0E-01 Fish intake - DDR Alistipes shahii 1.02% 0.78 Red meat intake - DDR 0.0469 0.0491 3.4E-01 199 0.0556 0.0277 4.5E-02 726 6.7E-01 Fish intake - DDR Alistipes shahii 1.02% 0.78 Red meat intake - FFQ 0.0573 0.0484 2.4E-01 199 0.0552 0.0279 4.8E-02 726 7.6E-01 Fish intake - DDR Alistipes shahii 1.02% 0.78 Clostridiales bacterium 1 7 47FAA 0.0326 0.0488 5.1E-01 199 0.0494 0.0273 7.1E-02 726 6.4E-01 Fish intake - DDR Alistipes shahii 1.02% 0.78 Clostridium citroniae 0.0342 0.0487 4.8E-01 199 0.0431 0.0273 1.1E-01 726 7.4E-01 Fish intake - DDR Alistipes shahii 1.02% 0.78 Clostridium clostridioforme 0.0443 0.0488 3.6E-01 199 0.0520 0.0272 5.6E-02 726 6.7E-01 Fish intake - DDR Alistipes shahii 1.02% 0.78 Clostridium nexile 0.0495 0.0489 3.1E-01 199 0.0473 0.0275 8.6E-02 726 8.3E-01 Fish intake - DDR Alistipes shahii 1.02% 0.78 Eggerthella (unclassified) 0.0354 0.0485 4.7E-01 199 0.0485 0.0275 7.8E-02 726 7.4E-01 Fish intake - DDR Alistipes shahii 1.02% 0.78 Erysipelotrichaceae bacterium 21 3 0.0512 0.0484 2.9E-01 199 0.0475 0.0276 8.6E-02 726 8.0E-01 Fish intake - DDR Alistipes shahii 1.02% 0.78 Roseburia hominis 0.0436 0.0488 3.7E-01 199 0.0474 0.0271 8.1E-02 726 8.6E-01 Red meat intake - FFQ Eubacterium biforme 0.26% 0.24 Fully adjusted 0.0742 0.0729 3.1E-01 699 -0.0852 0.1449 5.6E-01 226 2.6E-02 Red meat intake - FFQ Eubacterium biforme 0.26% 0.24 Choline intake - DDR 0.0627 0.0732 3.9E-01 699 -0.0937 0.1449 5.2E-01 226 2.8E-02 Red meat intake - FFQ Eubacterium biforme 0.26% 0.24 Choline intake - FFQ 0.0764 0.0775 3.2E-01 699 -0.0906 0.1603 5.7E-01 226 2.2E-02 Red meat intake - FFQ Eubacterium biforme 0.26% 0.24 Dairy intake - DDR 0.0819 0.0730 2.6E-01 699 -0.0899 0.1459 5.4E-01 226 2.6E-02 Red meat intake - FFQ Eubacterium biforme 0.26% 0.24 Dairy intake - FFQ 0.0861 0.0726 2.4E-01 699 -0.0657 0.1465 6.5E-01 226 3.1E-02 Red meat intake - FFQ Eubacterium biforme 0.26% 0.24 Egg intake - DDR 0.0669 0.0733 3.6E-01 699 -0.0840 0.1458 5.7E-01 226 2.6E-02 Red meat intake - FFQ Eubacterium biforme 0.26% 0.24 Egg intake - FFQ 0.0566 0.0741 4.5E-01 699 -0.0811 0.1454 5.8E-01 226 3.9E-02 Red meat intake - FFQ Eubacterium biforme 0.26% 0.24 Eubacterium hallii 0.0773 0.0723 2.9E-01 699 -0.0890 0.1448 5.4E-01 226 2.4E-02 Red meat intake - FFQ Eubacterium biforme 0.26% 0.24 Fish intake - DDR 0.0657 0.0733 3.7E-01 699 -0.0404 0.1472 7.8E-01 226 4.4E-02 Red meat intake - FFQ Eubacterium biforme 0.26% 0.24 Fish intake - FFQ 0.0782 0.0730 2.8E-01 699 -0.0808 0.1460 5.8E-01 226 2.3E-02 Red meat intake - FFQ Eubacterium biforme 0.26% 0.24 Plasma choline 0.0696 0.0727 3.4E-01 699 -0.0807 0.1458 5.8E-01 226 3.2E-02 Red meat intake - FFQ Eubacterium biforme 0.26% 0.24 Plasma L-carnitine 0.0720 0.0731 3.2E-01 699 -0.0800 0.1437 5.8E-01 226 2.6E-02 Red meat intake - FFQ Eubacterium biforme 0.26% 0.24 Red meat intake - DDR 0.0345 0.0815 6.7E-01 699 -0.1585 0.1505 2.9E-01 226 2.2E-02 Red meat intake - FFQ Eubacterium biforme 0.26% 0.24 Alistipes shahii 0.0737 0.0732 3.1E-01 699 -0.1163 0.1444 4.2E-01 226 2.6E-02 Red meat intake - FFQ Eubacterium biforme 0.26% 0.24 Clostridiales bacterium 1 7 47FAA 0.0609 0.0725 4.0E-01 699 -0.0870 0.1455 5.5E-01 226 3.2E-02 Red meat intake - FFQ Eubacterium biforme 0.26% 0.24 Clostridium citroniae 0.0950 0.0730 1.9E-01 699 -0.0992 0.1442 4.9E-01 226 2.0E-02 Red meat intake - FFQ Eubacterium biforme 0.26% 0.24 Clostridium clostridioforme 0.0695 0.0716 3.3E-01 699 -0.1069 0.1442 4.6E-01 226 3.5E-02 Red meat intake - FFQ Eubacterium biforme 0.26% 0.24 Clostridium nexile 0.0718 0.0724 3.2E-01 699 -0.0953 0.1447 5.1E-01 226 2.8E-02 Red meat intake - FFQ Eubacterium biforme 0.26% 0.24 Eggerthella (unclassified) 0.0791 0.0731 2.8E-01 699 -0.1045 0.1425 4.6E-01 226 2.4E-02 Red meat intake - FFQ Eubacterium biforme 0.26% 0.24 Erysipelotrichaceae bacterium 21 3 0.0756 0.0730 3.0E-01 699 -0.1611 0.1487 2.8E-01 226 2.8E-02 Red meat intake - FFQ Eubacterium biforme 0.26% 0.24 Roseburia hominis 0.0730 0.0725 3.1E-01 699 -0.0848 0.1411 5.5E-01 226 2.9E-02 Red meat intake - DDR Eubacterium biforme 0.26% 0.24 Fully adjusted 0.0345 0.0214 1.1E-01 699 0.0575 0.0363 1.1E-01 226 2.9E-01 Red meat intake - DDR Eubacterium biforme 0.26% 0.24 Choline intake - DDR 0.0223 0.0230 3.3E-01 699 0.0411 0.0378 2.8E-01 226 3.4E-01 Red meat intake - DDR Eubacterium biforme 0.26% 0.24 Choline intake - FFQ 0.0354 0.0220 1.1E-01 699 0.0641 0.0368 8.4E-02 226 3.1E-01 Red meat intake - DDR Eubacterium biforme 0.26% 0.24 Dairy intake - DDR 0.0388 0.0214 7.1E-02 699 0.0574 0.0364 1.2E-01 226 2.4E-01 Red meat intake - DDR Eubacterium biforme 0.26% 0.24 Dairy intake - FFQ 0.0401 0.0215 6.3E-02 699 0.0567 0.0360 1.2E-01 226 2.4E-01 Red meat intake - DDR Eubacterium biforme 0.26% 0.24 Egg intake - DDR 0.0323 0.0216 1.4E-01 699 0.0581 0.0365 1.1E-01 226 3.2E-01 Red meat intake - DDR Eubacterium biforme 0.26% 0.24 Egg intake - FFQ 0.0359 0.0217 9.9E-02 699 0.0593 0.0363 1.0E-01 226 3.2E-01 Red meat intake - DDR Eubacterium biforme 0.26% 0.24 Eubacterium hallii 0.0350 0.0212 1.0E-01 699 0.0542 0.0362 1.4E-01 226 2.8E-01 Red meat intake - DDR Eubacterium biforme 0.26% 0.24 Fish intake - DDR 0.0348 0.0215 1.1E-01 699 0.0583 0.0364 1.1E-01 226 2.9E-01 Red meat intake - DDR Eubacterium biforme 0.26% 0.24 Fish intake - FFQ 0.0398 0.0215 6.5E-02 699 0.0501 0.0365 1.7E-01 226 2.1E-01 Red meat intake - DDR Eubacterium biforme 0.26% 0.24 Plasma choline 0.0333 0.0213 1.2E-01 699 0.0555 0.0365 1.3E-01 226 3.1E-01 Red meat intake - DDR Eubacterium biforme 0.26% 0.24 Plasma L-carnitine 0.0325 0.0217 1.3E-01 699 0.0537 0.0360 1.4E-01 226 3.5E-01 Red meat intake - DDR Eubacterium biforme 0.26% 0.24 Red meat intake - FFQ 0.0408 0.0235 8.4E-02 699 0.0573 0.0379 1.3E-01 226 2.6E-01 Red meat intake - DDR Eubacterium biforme 0.26% 0.24 Alistipes shahii 0.0345 0.0214 1.1E-01 699 0.0609 0.0360 9.2E-02 226 3.0E-01 Red meat intake - DDR Eubacterium biforme 0.26% 0.24 Clostridiales bacterium 1 7 47FAA 0.0300 0.0213 1.6E-01 699 0.0571 0.0364 1.2E-01 226 3.5E-01 Red meat intake - DDR Eubacterium biforme 0.26% 0.24 Clostridium citroniae 0.0330 0.0213 1.2E-01 699 0.0547 0.0362 1.3E-01 226 3.3E-01 Red meat intake - DDR Eubacterium biforme 0.26% 0.24 Clostridium clostridioforme 0.0386 0.0210 6.7E-02 699 0.0520 0.0361 1.5E-01 226 2.7E-01 Red meat intake - DDR Eubacterium biforme 0.26% 0.24 Clostridium nexile 0.0316 0.0213 1.4E-01 699 0.0638 0.0364 8.1E-02 226 3.4E-01 Red meat intake - DDR Eubacterium biforme 0.26% 0.24 Eggerthella (unclassified) 0.0373 0.0216 8.5E-02 699 0.0573 0.0359 1.1E-01 226 2.5E-01 Red meat intake - DDR Eubacterium biforme 0.26% 0.24 Erysipelotrichaceae bacterium 21 3 0.0349 0.0214 1.0E-01 699 0.0559 0.0362 1.2E-01 226 2.9E-01 Red meat intake - DDR Eubacterium biforme 0.26% 0.24 Roseburia hominis 0.0344 0.0213 1.1E-01 699 0.0637 0.0352 7.2E-02 226 3.6E-01 Choline intake - FFQ Eubacterium biforme 0.26% 0.24 Fully adjusted 0.1085 0.0586 6.4E-02 699 0.0594 0.1183 6.2E-01 226 8.6E-02 Choline intake - FFQ Eubacterium biforme 0.26% 0.24 Choline intake - DDR 0.0888 0.0633 1.6E-01 699 0.0036 0.1284 9.8E-01 226 9.0E-02 Choline intake - FFQ Eubacterium biforme 0.26% 0.24 Dairy intake - DDR 0.0987 0.0589 9.4E-02 699 0.0726 0.1218 5.5E-01 226 9.1E-02 Choline intake - FFQ Eubacterium biforme 0.26% 0.24 Dairy intake - FFQ 0.0690 0.0614 2.6E-01 699 0.0373 0.1216 7.6E-01 226 7.1E-02 Choline intake - FFQ Eubacterium biforme 0.26% 0.24 Egg intake - DDR 0.1047 0.0604 8.4E-02 699 0.0624 0.1282 6.3E-01 226 8.8E-02 Choline intake - FFQ Eubacterium biforme 0.26% 0.24 Egg intake - FFQ 0.0841 0.0666 2.1E-01 699 0.0160 0.1464 9.1E-01 226 1.1E-01 Choline intake - FFQ Eubacterium biforme 0.26% 0.24 Eubacterium hallii 0.1033 0.0580 7.5E-02 699 0.0374 0.1196 7.6E-01 226 1.5E-01 Choline intake - FFQ Eubacterium biforme 0.26% 0.24 Fish intake - DDR 0.1218 0.0581 3.6E-02 699 0.1123 0.1163 3.4E-01 226 5.7E-02 Choline intake - FFQ Eubacterium biforme 0.26% 0.24 Fish intake - FFQ 0.1057 0.0586 7.2E-02 699 0.0850 0.1181 4.7E-01 226 9.6E-02 Choline intake - FFQ Eubacterium biforme 0.26% 0.24 Plasma choline 0.1021 0.0585 8.1E-02 699 0.0572 0.1188 6.3E-01 226 6.2E-02 Choline intake - FFQ Eubacterium biforme 0.26% 0.24 Plasma L-carnitine 0.1061 0.0590 7.3E-02 699 0.0245 0.1185 8.4E-01 226 1.0E-01 Choline intake - FFQ Eubacterium biforme 0.26% 0.24 Red meat intake - DDR 0.0891 0.0604 1.4E-01 699 0.0672 0.1179 5.7E-01 226 6.9E-02 Choline intake - FFQ Eubacterium biforme 0.26% 0.24 Red meat intake - FFQ 0.0884 0.0609 1.5E-01 699 0.0781 0.1230 5.3E-01 226 6.8E-02 Choline intake - FFQ Eubacterium biforme 0.26% 0.24 Alistipes shahii 0.1101 0.0587 6.1E-02 699 0.0487 0.1176 6.8E-01 226 8.5E-02 Choline intake - FFQ Eubacterium biforme 0.26% 0.24 Clostridiales bacterium 1 7 47FAA 0.1111 0.0582 5.7E-02 699 0.0580 0.1190 6.3E-01 226 1.0E-01 Choline intake - FFQ Eubacterium biforme 0.26% 0.24 Clostridium citroniae 0.1089 0.0583 6.2E-02 699 0.0509 0.1177 6.7E-01 226 9.8E-02 Choline intake - FFQ Eubacterium biforme 0.26% 0.24 Clostridium clostridioforme 0.1067 0.0574 6.3E-02 699 0.0320 0.1185 7.9E-01 226 6.4E-02 Choline intake - FFQ Eubacterium biforme 0.26% 0.24 Clostridium nexile 0.0838 0.0587 1.5E-01 699 0.0569 0.1181 6.3E-01 226 4.5E-02 Choline intake - FFQ Eubacterium biforme 0.26% 0.24 Eggerthella (unclassified) 0.1067 0.0586 6.9E-02 699 0.0768 0.1164 5.1E-01 226 7.8E-02 Choline intake - FFQ Eubacterium biforme 0.26% 0.24 Erysipelotrichaceae bacterium 21 3 0.1062 0.0588 7.1E-02 699 0.0553 0.1177 6.4E-01 226 7.6E-02 Choline intake - FFQ Eubacterium biforme 0.26% 0.24 Roseburia hominis 0.1069 0.0583 6.7E-02 699 0.0734 0.1151 5.2E-01 226 8.3E-02 Choline intake - DDR Eubacterium biforme 0.26% 0.24 Fully adjusted 0.0860 0.0462 6.3E-02 699 0.1644 0.0861 5.8E-02 226 4.7E-01 24

Supplementary Data 2a Absence (species)/ Non- Presence (species)/ Stratified by Dietary Exposure Additionally conditioned on producer (mixed score) TMAO-producer (mixed P-interaction Taxa Abundance Prevalence Effect Se P n Effect Se P n Choline intake - DDR Eubacterium biforme 0.26% 0.24 Choline intake - FFQ 0.0787 0.0494 1.1E-01 699 0.1008 0.0949 2.9E-01 226 3.9E-01 Choline intake - DDR Eubacterium biforme 0.26% 0.24 Dairy intake - DDR 0.0801 0.0462 8.3E-02 699 0.1642 0.0864 5.9E-02 226 4.6E-01 Choline intake - DDR Eubacterium biforme 0.26% 0.24 Dairy intake - FFQ 0.0734 0.0470 1.2E-01 699 0.1507 0.0858 8.0E-02 226 3.8E-01 Choline intake - DDR Eubacterium biforme 0.26% 0.24 Egg intake - DDR 0.1061 0.0598 7.6E-02 699 0.2511 0.1237 4.4E-02 226 4.2E-01 Choline intake - DDR Eubacterium biforme 0.26% 0.24 Egg intake - FFQ 0.0844 0.0481 8.0E-02 699 0.1445 0.0938 1.2E-01 226 4.7E-01 Choline intake - DDR Eubacterium biforme 0.26% 0.24 Eubacterium hallii 0.0834 0.0458 6.9E-02 699 0.1490 0.0865 8.7E-02 226 5.6E-01 Choline intake - DDR Eubacterium biforme 0.26% 0.24 Fish intake - DDR 0.0944 0.0465 4.3E-02 699 0.1692 0.0868 5.3E-02 226 5.2E-01 Choline intake - DDR Eubacterium biforme 0.26% 0.24 Fish intake - FFQ 0.0897 0.0463 5.3E-02 699 0.1470 0.0869 9.2E-02 226 6.1E-01 Choline intake - DDR Eubacterium biforme 0.26% 0.24 Plasma choline 0.0823 0.0460 7.4E-02 699 0.1679 0.0863 5.3E-02 226 4.5E-01 Choline intake - DDR Eubacterium biforme 0.26% 0.24 Plasma L-carnitine 0.0828 0.0464 7.5E-02 699 0.1598 0.0853 6.3E-02 226 3.7E-01 Choline intake - DDR Eubacterium biforme 0.26% 0.24 Red meat intake - DDR 0.0724 0.0497 1.5E-01 699 0.1347 0.0899 1.4E-01 226 5.8E-01 Choline intake - DDR Eubacterium biforme 0.26% 0.24 Red meat intake - FFQ 0.0888 0.0468 5.8E-02 699 0.1618 0.0868 6.4E-02 226 4.4E-01 Choline intake - DDR Eubacterium biforme 0.26% 0.24 Alistipes shahii 0.0870 0.0463 6.0E-02 699 0.1705 0.0853 4.7E-02 226 4.5E-01 Choline intake - DDR Eubacterium biforme 0.26% 0.24 Clostridiales bacterium 1 7 47FAA 0.0802 0.0459 8.1E-02 699 0.1635 0.0864 6.0E-02 226 4.6E-01 Choline intake - DDR Eubacterium biforme 0.26% 0.24 Clostridium citroniae 0.0808 0.0460 8.0E-02 699 0.1613 0.0858 6.2E-02 226 4.6E-01 Choline intake - DDR Eubacterium biforme 0.26% 0.24 Clostridium clostridioforme 0.0844 0.0453 6.3E-02 699 0.1494 0.0857 8.3E-02 226 4.9E-01 Choline intake - DDR Eubacterium biforme 0.26% 0.24 Clostridium nexile 0.0769 0.0460 9.5E-02 699 0.1543 0.0864 7.5E-02 226 4.0E-01 Choline intake - DDR Eubacterium biforme 0.26% 0.24 Eggerthella (unclassified) 0.0862 0.0462 6.2E-02 699 0.1733 0.0850 4.3E-02 226 4.6E-01 Choline intake - DDR Eubacterium biforme 0.26% 0.24 Erysipelotrichaceae bacterium 21 3 0.0859 0.0462 6.3E-02 699 0.1581 0.0858 6.7E-02 226 4.6E-01 Choline intake - DDR Eubacterium biforme 0.26% 0.24 Roseburia hominis 0.0875 0.0460 5.7E-02 699 0.1946 0.0836 2.1E-02 226 3.2E-01 Plasma choline Eubacterium biforme 0.26% 0.24 Fully adjusted 0.0815 0.0371 2.9E-02 699 0.0315 0.0796 6.9E-01 226 4.6E-02 Plasma choline Eubacterium biforme 0.26% 0.24 Choline intake - DDR 0.0783 0.0372 3.6E-02 699 0.0180 0.0803 8.2E-01 226 4.5E-02 Plasma choline Eubacterium biforme 0.26% 0.24 Choline intake - FFQ 0.0829 0.0374 2.7E-02 699 0.0263 0.0812 7.5E-01 226 4.2E-02 Plasma choline Eubacterium biforme 0.26% 0.24 Dairy intake - DDR 0.0808 0.0371 3.0E-02 699 0.0381 0.0816 6.4E-01 226 3.7E-02 Plasma choline Eubacterium biforme 0.26% 0.24 Dairy intake - FFQ 0.0827 0.0370 2.6E-02 699 0.0266 0.0798 7.4E-01 226 4.1E-02 Plasma choline Eubacterium biforme 0.26% 0.24 Egg intake - DDR 0.0804 0.0372 3.1E-02 699 0.0309 0.0807 7.0E-01 226 4.5E-02 Plasma choline Eubacterium biforme 0.26% 0.24 Egg intake - FFQ 0.0804 0.0371 3.1E-02 699 0.0254 0.0807 7.5E-01 226 3.5E-02 Plasma choline Eubacterium biforme 0.26% 0.24 Eubacterium hallii 0.0780 0.0368 3.4E-02 699 0.0327 0.0795 6.8E-01 226 5.8E-02 Plasma choline Eubacterium biforme 0.26% 0.24 Fish intake - DDR 0.0838 0.0366 2.3E-02 699 0.0053 0.0786 9.5E-01 226 3.1E-02 Plasma choline Eubacterium biforme 0.26% 0.24 Fish intake - FFQ 0.0785 0.0371 3.5E-02 699 0.0102 0.0799 9.0E-01 226 5.7E-02 Plasma choline Eubacterium biforme 0.26% 0.24 Plasma L-carnitine 0.0809 0.0380 3.4E-02 699 -0.0338 0.0844 6.9E-01 226 3.3E-02 Plasma choline Eubacterium biforme 0.26% 0.24 Red meat intake - DDR 0.0770 0.0372 3.9E-02 699 0.0332 0.0792 6.8E-01 226 5.3E-02 Plasma choline Eubacterium biforme 0.26% 0.24 Red meat intake - FFQ 0.0884 0.0373 1.8E-02 699 0.0274 0.0801 7.3E-01 226 3.9E-02 Plasma choline Eubacterium biforme 0.26% 0.24 Alistipes shahii 0.0822 0.0372 2.8E-02 699 0.0321 0.0790 6.9E-01 226 4.3E-02 Plasma choline Eubacterium biforme 0.26% 0.24 Clostridiales bacterium 1 7 47FAA 0.0829 0.0369 2.5E-02 699 0.0311 0.0798 7.0E-01 226 4.7E-02 Plasma choline Eubacterium biforme 0.26% 0.24 Clostridium citroniae 0.0769 0.0370 3.8E-02 699 0.0361 0.0792 6.5E-01 226 5.9E-02 Plasma choline Eubacterium biforme 0.26% 0.24 Clostridium clostridioforme 0.0984 0.0365 7.3E-03 699 0.0350 0.0790 6.6E-01 226 3.2E-02 Plasma choline Eubacterium biforme 0.26% 0.24 Clostridium nexile 0.0931 0.0370 1.2E-02 699 0.0266 0.0795 7.4E-01 226 2.8E-02 Plasma choline Eubacterium biforme 0.26% 0.24 Eggerthella (unclassified) 0.0806 0.0372 3.0E-02 699 0.0574 0.0787 4.7E-01 226 5.4E-02 Plasma choline Eubacterium biforme 0.26% 0.24 Erysipelotrichaceae bacterium 21 3 0.0844 0.0373 2.4E-02 699 0.0392 0.0793 6.2E-01 226 4.0E-02 Plasma choline Eubacterium biforme 0.26% 0.24 Roseburia hominis 0.0868 0.0370 1.9E-02 699 0.0704 0.0781 3.7E-01 226 5.9E-02 Plasma L-carnitine Eubacterium biforme 0.26% 0.24 Fully adjusted 0.0187 0.0358 6.0E-01 699 0.1485 0.0679 3.0E-02 226 1.7E-01 Plasma L-carnitine Eubacterium biforme 0.26% 0.24 Choline intake - DDR 0.0106 0.0362 7.7E-01 699 0.1525 0.0678 2.6E-02 226 1.2E-01 Plasma L-carnitine Eubacterium biforme 0.26% 0.24 Choline intake - FFQ 0.0122 0.0365 7.4E-01 699 0.1452 0.0699 3.9E-02 226 1.7E-01 Plasma L-carnitine Eubacterium biforme 0.26% 0.24 Dairy intake - DDR 0.0134 0.0359 7.1E-01 699 0.1638 0.0702 2.1E-02 226 1.9E-01 Plasma L-carnitine Eubacterium biforme 0.26% 0.24 Dairy intake - FFQ 0.0135 0.0357 7.1E-01 699 0.1410 0.0690 4.2E-02 226 1.8E-01 Plasma L-carnitine Eubacterium biforme 0.26% 0.24 Egg intake - DDR 0.0174 0.0358 6.3E-01 699 0.1486 0.0683 3.1E-02 226 1.7E-01 Plasma L-carnitine Eubacterium biforme 0.26% 0.24 Egg intake - FFQ 0.0163 0.0358 6.5E-01 699 0.1460 0.0685 3.4E-02 226 1.9E-01 Plasma L-carnitine Eubacterium biforme 0.26% 0.24 Eubacterium hallii 0.0243 0.0355 4.9E-01 699 0.1385 0.0688 4.6E-02 226 2.6E-01 Plasma L-carnitine Eubacterium biforme 0.26% 0.24 Fish intake - DDR 0.0209 0.0354 5.6E-01 699 0.1599 0.0704 2.4E-02 226 1.4E-01 Plasma L-carnitine Eubacterium biforme 0.26% 0.24 Fish intake - FFQ 0.0182 0.0358 6.1E-01 699 0.1368 0.0685 4.7E-02 226 1.7E-01 Plasma L-carnitine Eubacterium biforme 0.26% 0.24 Plasma choline 0.0024 0.0365 9.5E-01 699 0.1588 0.0728 3.0E-02 226 1.8E-01 Plasma L-carnitine Eubacterium biforme 0.26% 0.24 Red meat intake - DDR 0.0072 0.0363 8.4E-01 699 0.1489 0.0678 2.9E-02 226 1.2E-01 Plasma L-carnitine Eubacterium biforme 0.26% 0.24 Red meat intake - FFQ 0.0158 0.0358 6.6E-01 699 0.1479 0.0680 3.1E-02 226 1.6E-01 Plasma L-carnitine Eubacterium biforme 0.26% 0.24 Alistipes shahii 0.0184 0.0359 6.1E-01 699 0.1519 0.0673 2.5E-02 226 1.7E-01 Plasma L-carnitine Eubacterium biforme 0.26% 0.24 Clostridiales bacterium 1 7 47FAA 0.0173 0.0355 6.3E-01 699 0.1483 0.0681 3.0E-02 226 1.6E-01 Plasma L-carnitine Eubacterium biforme 0.26% 0.24 Clostridium citroniae 0.0194 0.0356 5.9E-01 699 0.1523 0.0675 2.5E-02 226 1.8E-01 Plasma L-carnitine Eubacterium biforme 0.26% 0.24 Clostridium clostridioforme 0.0149 0.0351 6.7E-01 699 0.1582 0.0674 2.0E-02 226 1.5E-01 Plasma L-carnitine Eubacterium biforme 0.26% 0.24 Clostridium nexile 0.0278 0.0356 4.4E-01 699 0.1395 0.0682 4.2E-02 226 2.0E-01 Plasma L-carnitine Eubacterium biforme 0.26% 0.24 Eggerthella (unclassified) 0.0217 0.0360 5.5E-01 699 0.1246 0.0676 6.7E-02 226 2.2E-01 Plasma L-carnitine Eubacterium biforme 0.26% 0.24 Erysipelotrichaceae bacterium 21 3 0.0196 0.0358 5.8E-01 699 0.1599 0.0676 1.9E-02 226 1.7E-01 Plasma L-carnitine Eubacterium biforme 0.26% 0.24 Roseburia hominis 0.0284 0.0357 4.3E-01 699 0.1874 0.0664 5.2E-03 226 1.7E-01 Dairy intake - FFQ Eubacterium biforme 0.26% 0.24 Fully adjusted 0.0700 0.0275 1.1E-02 699 0.0671 0.0673 3.2E-01 226 6.4E-01 Dairy intake - FFQ Eubacterium biforme 0.26% 0.24 Choline intake - DDR 0.0636 0.0281 2.4E-02 699 0.0584 0.0677 3.9E-01 226 6.4E-01 Dairy intake - FFQ Eubacterium biforme 0.26% 0.24 Choline intake - FFQ 0.0617 0.0296 3.7E-02 699 0.0588 0.0734 4.2E-01 226 8.0E-01 Dairy intake - FFQ Eubacterium biforme 0.26% 0.24 Dairy intake - DDR 0.0646 0.0326 4.8E-02 699 0.1331 0.0870 1.3E-01 226 6.2E-01 Dairy intake - FFQ Eubacterium biforme 0.26% 0.24 Egg intake - DDR 0.0712 0.0275 9.8E-03 699 0.0692 0.0681 3.1E-01 226 7.1E-01 Dairy intake - FFQ Eubacterium biforme 0.26% 0.24 Egg intake - FFQ 0.0686 0.0275 1.3E-02 699 0.0625 0.0684 3.6E-01 226 7.6E-01 Dairy intake - FFQ Eubacterium biforme 0.26% 0.24 Eubacterium hallii 0.0688 0.0272 1.2E-02 699 0.0814 0.0679 2.3E-01 226 5.8E-01 Dairy intake - FFQ Eubacterium biforme 0.26% 0.24 Fish intake - DDR 0.0633 0.0275 2.2E-02 699 0.0773 0.0677 2.5E-01 226 4.7E-01 Dairy intake - FFQ Eubacterium biforme 0.26% 0.24 Fish intake - FFQ 0.0723 0.0275 8.9E-03 699 0.0683 0.0679 3.2E-01 226 7.2E-01 Dairy intake - FFQ Eubacterium biforme 0.26% 0.24 Plasma choline 0.0708 0.0274 1.0E-02 699 0.0657 0.0676 3.3E-01 226 6.5E-01 Dairy intake - FFQ Eubacterium biforme 0.26% 0.24 Plasma L-carnitine 0.0694 0.0275 1.2E-02 699 0.0438 0.0678 5.2E-01 226 7.5E-01 Dairy intake - FFQ Eubacterium biforme 0.26% 0.24 Red meat intake - DDR 0.0714 0.0275 9.5E-03 699 0.0651 0.0671 3.3E-01 226 6.9E-01 Dairy intake - FFQ Eubacterium biforme 0.26% 0.24 Red meat intake - FFQ 0.0808 0.0277 3.7E-03 699 0.0626 0.0682 3.6E-01 226 6.7E-01 Dairy intake - FFQ Eubacterium biforme 0.26% 0.24 Alistipes shahii 0.0702 0.0275 1.1E-02 699 0.0584 0.0670 3.8E-01 226 6.4E-01 Dairy intake - FFQ Eubacterium biforme 0.26% 0.24 Clostridiales bacterium 1 7 47FAA 0.0722 0.0273 8.3E-03 699 0.0675 0.0675 3.2E-01 226 7.2E-01 Dairy intake - FFQ Eubacterium biforme 0.26% 0.24 Clostridium citroniae 0.0715 0.0274 9.2E-03 699 0.0697 0.0669 3.0E-01 226 6.3E-01 Dairy intake - FFQ Eubacterium biforme 0.26% 0.24 Clostridium clostridioforme 0.0637 0.0270 1.9E-02 699 0.0894 0.0675 1.9E-01 226 7.2E-01 Dairy intake - FFQ Eubacterium biforme 0.26% 0.24 Clostridium nexile 0.0646 0.0273 1.8E-02 699 0.0697 0.0672 3.0E-01 226 5.7E-01 25

Supplementary Data 2a Absence (species)/ Non- Presence (species)/ Stratified by Dietary Exposure Additionally conditioned on producer (mixed score) TMAO-producer (mixed P-interaction Taxa Abundance Prevalence Effect Se P n Effect Se P n Dairy intake - FFQ Eubacterium biforme 0.26% 0.24 Eggerthella (unclassified) 0.0690 0.0275 1.2E-02 699 0.0584 0.0663 3.8E-01 226 6.4E-01 Dairy intake - FFQ Eubacterium biforme 0.26% 0.24 Erysipelotrichaceae bacterium 21 3 0.0694 0.0275 1.2E-02 699 0.0653 0.0670 3.3E-01 226 6.1E-01 Dairy intake - FFQ Eubacterium biforme 0.26% 0.24 Roseburia hominis 0.0726 0.0273 8.1E-03 699 0.0881 0.0657 1.8E-01 226 6.0E-01 Dairy intake - DDR Eubacterium biforme 0.26% 0.24 Fully adjusted 0.0569 0.0283 4.5E-02 699 0.0079 0.0571 8.9E-01 226 1.1E-01 Dairy intake - DDR Eubacterium biforme 0.26% 0.24 Choline intake - DDR 0.0536 0.0283 5.9E-02 699 0.0053 0.0567 9.3E-01 226 1.2E-01 Dairy intake - DDR Eubacterium biforme 0.26% 0.24 Choline intake - FFQ 0.0603 0.0289 3.7E-02 699 -0.0230 0.0582 6.9E-01 226 7.6E-02 Dairy intake - DDR Eubacterium biforme 0.26% 0.24 Dairy intake - FFQ 0.0451 0.0321 1.6E-01 699 -0.1025 0.0710 1.5E-01 226 1.2E-01 Dairy intake - DDR Eubacterium biforme 0.26% 0.24 Egg intake - DDR 0.0608 0.0285 3.3E-02 699 0.0073 0.0573 9.0E-01 226 1.0E-01 Dairy intake - DDR Eubacterium biforme 0.26% 0.24 Egg intake - FFQ 0.0611 0.0284 3.2E-02 699 -0.0090 0.0586 8.8E-01 226 6.5E-02 Dairy intake - DDR Eubacterium biforme 0.26% 0.24 Eubacterium hallii 0.0571 0.0280 4.2E-02 699 0.0112 0.0569 8.4E-01 226 1.1E-01 Dairy intake - DDR Eubacterium biforme 0.26% 0.24 Fish intake - DDR 0.0535 0.0284 6.1E-02 699 0.0070 0.0573 9.0E-01 226 1.3E-01 Dairy intake - DDR Eubacterium biforme 0.26% 0.24 Fish intake - FFQ 0.0546 0.0284 5.5E-02 699 0.0015 0.0570 9.8E-01 226 1.2E-01 Dairy intake - DDR Eubacterium biforme 0.26% 0.24 Plasma choline 0.0590 0.0282 3.7E-02 699 0.0132 0.0576 8.2E-01 226 8.8E-02 Dairy intake - DDR Eubacterium biforme 0.26% 0.24 Plasma L-carnitine 0.0553 0.0284 5.1E-02 699 -0.0247 0.0583 6.7E-01 226 8.6E-02 Dairy intake - DDR Eubacterium biforme 0.26% 0.24 Red meat intake - DDR 0.0607 0.0284 3.3E-02 699 0.0173 0.0574 7.6E-01 226 9.5E-02 Dairy intake - DDR Eubacterium biforme 0.26% 0.24 Red meat intake - FFQ 0.0608 0.0284 3.3E-02 699 0.0112 0.0576 8.5E-01 226 1.1E-01 Dairy intake - DDR Eubacterium biforme 0.26% 0.24 Alistipes shahii 0.0580 0.0284 4.1E-02 699 0.0060 0.0565 9.2E-01 226 1.1E-01 Dairy intake - DDR Eubacterium biforme 0.26% 0.24 Clostridiales bacterium 1 7 47FAA 0.0637 0.0281 2.4E-02 699 0.0091 0.0573 8.7E-01 226 7.8E-02 Dairy intake - DDR Eubacterium biforme 0.26% 0.24 Clostridium citroniae 0.0634 0.0282 2.5E-02 699 0.0087 0.0568 8.8E-01 226 1.0E-01 Dairy intake - DDR Eubacterium biforme 0.26% 0.24 Clostridium clostridioforme 0.0530 0.0278 5.7E-02 699 0.0700 0.0616 2.6E-01 226 4.2E-02 Dairy intake - DDR Eubacterium biforme 0.26% 0.24 Clostridium nexile 0.0627 0.0281 2.6E-02 699 -0.0014 0.0573 9.8E-01 226 9.5E-02 Dairy intake - DDR Eubacterium biforme 0.26% 0.24 Eggerthella (unclassified) 0.0575 0.0283 4.3E-02 699 -0.0029 0.0565 9.6E-01 226 1.0E-01 Dairy intake - DDR Eubacterium biforme 0.26% 0.24 Erysipelotrichaceae bacterium 21 3 0.0565 0.0284 4.7E-02 699 0.0115 0.0568 8.4E-01 226 1.3E-01 Dairy intake - DDR Eubacterium biforme 0.26% 0.24 Roseburia hominis 0.0611 0.0282 3.0E-02 699 0.0196 0.0555 7.2E-01 226 1.1E-01 Egg intake - FFQ Eubacterium biforme 0.26% 0.24 Fully adjusted 0.1223 0.0955 2.0E-01 699 0.0900 0.1603 5.8E-01 226 8.1E-01 Egg intake - FFQ Eubacterium biforme 0.26% 0.24 Choline intake - DDR 0.0931 0.0979 3.4E-01 699 0.0187 0.1726 9.1E-01 226 8.7E-01 Egg intake - FFQ Eubacterium biforme 0.26% 0.24 Choline intake - FFQ 0.0847 0.1097 4.4E-01 699 0.1051 0.2078 6.1E-01 226 9.2E-01 Egg intake - FFQ Eubacterium biforme 0.26% 0.24 Dairy intake - DDR 0.1349 0.0956 1.6E-01 699 0.1084 0.1659 5.1E-01 226 9.3E-01 Egg intake - FFQ Eubacterium biforme 0.26% 0.24 Dairy intake - FFQ 0.1117 0.0952 2.4E-01 699 0.0650 0.1627 6.9E-01 226 8.7E-01 Egg intake - FFQ Eubacterium biforme 0.26% 0.24 Egg intake - DDR 0.1024 0.1057 3.3E-01 699 0.1240 0.1923 5.2E-01 226 8.1E-01 Egg intake - FFQ Eubacterium biforme 0.26% 0.24 Eubacterium hallii 0.1343 0.0946 1.6E-01 699 0.0897 0.1601 5.8E-01 226 9.5E-01 Egg intake - FFQ Eubacterium biforme 0.26% 0.24 Fish intake - DDR 0.0973 0.0954 3.1E-01 699 0.0674 0.1608 6.8E-01 226 6.8E-01 Egg intake - FFQ Eubacterium biforme 0.26% 0.24 Fish intake - FFQ 0.1275 0.0955 1.8E-01 699 0.0773 0.1617 6.3E-01 226 8.2E-01 Egg intake - FFQ Eubacterium biforme 0.26% 0.24 Plasma choline 0.1174 0.0952 2.2E-01 699 0.0824 0.1625 6.1E-01 226 8.3E-01 Egg intake - FFQ Eubacterium biforme 0.26% 0.24 Plasma L-carnitine 0.1200 0.0957 2.1E-01 699 0.0516 0.1600 7.5E-01 226 8.8E-01 Egg intake - FFQ Eubacterium biforme 0.26% 0.24 Red meat intake - DDR 0.1030 0.0963 2.8E-01 699 0.0936 0.1595 5.6E-01 226 7.6E-01 Egg intake - FFQ Eubacterium biforme 0.26% 0.24 Red meat intake - FFQ 0.1275 0.0974 1.9E-01 699 0.0852 0.1608 6.0E-01 226 8.3E-01 Egg intake - FFQ Eubacterium biforme 0.26% 0.24 Alistipes shahii 0.1216 0.0957 2.0E-01 699 0.0810 0.1591 6.1E-01 226 7.9E-01 Egg intake - FFQ Eubacterium biforme 0.26% 0.24 Clostridiales bacterium 1 7 47FAA 0.1148 0.0948 2.3E-01 699 0.0883 0.1614 5.8E-01 226 7.6E-01 Egg intake - FFQ Eubacterium biforme 0.26% 0.24 Clostridium citroniae 0.1057 0.0953 2.7E-01 699 0.1016 0.1594 5.2E-01 226 7.2E-01 Egg intake - FFQ Eubacterium biforme 0.26% 0.24 Clostridium clostridioforme 0.1280 0.0937 1.7E-01 699 0.0904 0.1591 5.7E-01 226 7.9E-01 Egg intake - FFQ Eubacterium biforme 0.26% 0.24 Clostridium nexile 0.1039 0.0950 2.7E-01 699 0.0845 0.1600 6.0E-01 226 6.9E-01 Egg intake - FFQ Eubacterium biforme 0.26% 0.24 Eggerthella (unclassified) 0.1183 0.0956 2.2E-01 699 0.1204 0.1578 4.5E-01 226 7.4E-01 Egg intake - FFQ Eubacterium biforme 0.26% 0.24 Erysipelotrichaceae bacterium 21 3 0.1184 0.0959 2.2E-01 699 0.1055 0.1596 5.1E-01 226 7.6E-01 Egg intake - FFQ Eubacterium biforme 0.26% 0.24 Roseburia hominis 0.1114 0.0950 2.4E-01 699 0.1720 0.1574 2.8E-01 226 5.8E-01 Egg intake - DDR Eubacterium biforme 0.26% 0.24 Fully adjusted 0.0537 0.0697 4.4E-01 699 0.0922 0.1351 5.0E-01 226 8.2E-01 Egg intake - DDR Eubacterium biforme 0.26% 0.24 Choline intake - DDR -0.0477 0.0900 6.0E-01 699 -0.1694 0.1860 3.6E-01 226 7.3E-01 Egg intake - DDR Eubacterium biforme 0.26% 0.24 Choline intake - FFQ 0.0241 0.0732 7.4E-01 699 -0.0448 0.1489 7.6E-01 226 8.2E-01 Egg intake - DDR Eubacterium biforme 0.26% 0.24 Dairy intake - DDR 0.0734 0.0701 3.0E-01 699 0.0920 0.1354 5.0E-01 226 7.3E-01 Egg intake - DDR Eubacterium biforme 0.26% 0.24 Dairy intake - FFQ 0.0486 0.0697 4.9E-01 699 0.0522 0.1355 7.0E-01 226 7.5E-01 Egg intake - DDR Eubacterium biforme 0.26% 0.24 Egg intake - FFQ 0.0345 0.0777 6.6E-01 699 0.0019 0.1614 9.9E-01 226 7.8E-01 Egg intake - DDR Eubacterium biforme 0.26% 0.24 Eubacterium hallii 0.0628 0.0691 3.6E-01 699 0.0923 0.1345 4.9E-01 226 7.4E-01 Egg intake - DDR Eubacterium biforme 0.26% 0.24 Fish intake - DDR 0.0593 0.0701 4.0E-01 699 0.0904 0.1356 5.1E-01 226 8.0E-01 Egg intake - DDR Eubacterium biforme 0.26% 0.24 Fish intake - FFQ 0.0494 0.0698 4.8E-01 699 0.0675 0.1356 6.2E-01 226 7.1E-01 Egg intake - DDR Eubacterium biforme 0.26% 0.24 Plasma choline 0.0476 0.0695 4.9E-01 699 0.0961 0.1353 4.8E-01 226 8.3E-01 Egg intake - DDR Eubacterium biforme 0.26% 0.24 Plasma L-carnitine 0.0522 0.0697 4.5E-01 699 0.0940 0.1338 4.8E-01 226 8.4E-01 Egg intake - DDR Eubacterium biforme 0.26% 0.24 Red meat intake - DDR 0.0519 0.0711 4.7E-01 699 0.1058 0.1348 4.3E-01 226 8.6E-01 Egg intake - DDR Eubacterium biforme 0.26% 0.24 Red meat intake - FFQ 0.0521 0.0706 4.6E-01 699 0.0880 0.1357 5.2E-01 226 8.5E-01 Egg intake - DDR Eubacterium biforme 0.26% 0.24 Alistipes shahii 0.0534 0.0697 4.4E-01 699 0.1234 0.1344 3.6E-01 226 8.5E-01 Egg intake - DDR Eubacterium biforme 0.26% 0.24 Clostridiales bacterium 1 7 47FAA 0.0550 0.0691 4.3E-01 699 0.0907 0.1355 5.0E-01 226 8.4E-01 Egg intake - DDR Eubacterium biforme 0.26% 0.24 Clostridium citroniae 0.0571 0.0693 4.1E-01 699 0.0876 0.1346 5.2E-01 226 7.8E-01 Egg intake - DDR Eubacterium biforme 0.26% 0.24 Clostridium clostridioforme 0.0511 0.0683 4.5E-01 699 0.0627 0.1346 6.4E-01 226 9.2E-01 Egg intake - DDR Eubacterium biforme 0.26% 0.24 Clostridium nexile 0.0414 0.0693 5.5E-01 699 0.0682 0.1360 6.2E-01 226 8.9E-01 Egg intake - DDR Eubacterium biforme 0.26% 0.24 Eggerthella (unclassified) 0.0548 0.0697 4.3E-01 699 0.1230 0.1339 3.6E-01 226 8.4E-01 Egg intake - DDR Eubacterium biforme 0.26% 0.24 Erysipelotrichaceae bacterium 21 3 0.0535 0.0697 4.4E-01 699 0.0842 0.1344 5.3E-01 226 8.3E-01 Egg intake - DDR Eubacterium biforme 0.26% 0.24 Roseburia hominis 0.0526 0.0693 4.5E-01 699 0.1668 0.1322 2.1E-01 226 9.4E-01 Fish intake - FFQ Eubacterium biforme 0.26% 0.24 Fully adjusted 0.3366 0.1496 2.5E-02 699 0.3610 0.2736 1.9E-01 226 9.8E-03 Fish intake - FFQ Eubacterium biforme 0.26% 0.24 Choline intake - DDR 0.3582 0.1500 1.7E-02 699 0.3013 0.2766 2.8E-01 226 1.8E-02 Fish intake - FFQ Eubacterium biforme 0.26% 0.24 Choline intake - FFQ 0.3471 0.1568 2.7E-02 699 0.3771 0.2889 1.9E-01 226 9.4E-03 Fish intake - FFQ Eubacterium biforme 0.26% 0.24 Dairy intake - DDR 0.3368 0.1494 2.5E-02 699 0.3594 0.2742 1.9E-01 226 9.7E-03 Fish intake - FFQ Eubacterium biforme 0.26% 0.24 Dairy intake - FFQ 0.3808 0.1499 1.1E-02 699 0.3426 0.2742 2.1E-01 226 1.6E-02 Fish intake - FFQ Eubacterium biforme 0.26% 0.24 Egg intake - DDR 0.3406 0.1496 2.3E-02 699 0.3622 0.2753 1.9E-01 226 1.1E-02 Fish intake - FFQ Eubacterium biforme 0.26% 0.24 Egg intake - FFQ 0.3551 0.1501 1.8E-02 699 0.3777 0.2763 1.7E-01 226 1.2E-02 Fish intake - FFQ Eubacterium biforme 0.26% 0.24 Eubacterium hallii 0.3224 0.1483 3.0E-02 699 0.3448 0.2732 2.1E-01 226 1.5E-02 Fish intake - FFQ Eubacterium biforme 0.26% 0.24 Fish intake - DDR 0.3370 0.1544 2.9E-02 699 0.2401 0.3016 4.3E-01 226 1.4E-02 Fish intake - FFQ Eubacterium biforme 0.26% 0.24 Plasma choline 0.3487 0.1493 2.0E-02 699 0.3707 0.2846 1.9E-01 226 5.6E-03 Fish intake - FFQ Eubacterium biforme 0.26% 0.24 Plasma L-carnitine 0.3384 0.1497 2.4E-02 699 0.4635 0.2764 9.5E-02 226 8.7E-03 Fish intake - FFQ Eubacterium biforme 0.26% 0.24 Red meat intake - DDR 0.3561 0.1504 1.8E-02 699 0.3152 0.2740 2.5E-01 226 1.4E-02 Fish intake - FFQ Eubacterium biforme 0.26% 0.24 Red meat intake - FFQ 0.3664 0.1501 1.5E-02 699 0.3702 0.2745 1.8E-01 226 1.1E-02 Fish intake - FFQ Eubacterium biforme 0.26% 0.24 Alistipes shahii 0.3347 0.1499 2.6E-02 699 0.3945 0.2716 1.5E-01 226 8.8E-03 26

Supplementary Data 2a Absence (species)/ Non- Presence (species)/ Stratified by Dietary Exposure Additionally conditioned on producer (mixed score) TMAO-producer (mixed P-interaction Taxa Abundance Prevalence Effect Se P n Effect Se P n Fish intake - FFQ Eubacterium biforme 0.26% 0.24 Clostridiales bacterium 1 7 47FAA 0.3394 0.1485 2.3E-02 699 0.3728 0.2781 1.8E-01 226 1.6E-02 Fish intake - FFQ Eubacterium biforme 0.26% 0.24 Clostridium citroniae 0.3230 0.1490 3.0E-02 699 0.3374 0.2726 2.2E-01 226 1.4E-02 Fish intake - FFQ Eubacterium biforme 0.26% 0.24 Clostridium clostridioforme 0.3374 0.1468 2.2E-02 699 0.3767 0.2717 1.7E-01 226 1.0E-02 Fish intake - FFQ Eubacterium biforme 0.26% 0.24 Clostridium nexile 0.3568 0.1486 1.7E-02 699 0.3445 0.2733 2.1E-01 226 1.1E-02 Fish intake - FFQ Eubacterium biforme 0.26% 0.24 Eggerthella (unclassified) 0.3449 0.1499 2.2E-02 699 0.4269 0.2697 1.2E-01 226 1.1E-02 Fish intake - FFQ Eubacterium biforme 0.26% 0.24 Erysipelotrichaceae bacterium 21 3 0.3398 0.1497 2.4E-02 699 0.3751 0.2722 1.7E-01 226 1.2E-02 Fish intake - FFQ Eubacterium biforme 0.26% 0.24 Roseburia hominis 0.3342 0.1487 2.5E-02 699 0.4939 0.2695 6.8E-02 226 5.3E-03 Fish intake - DDR Eubacterium biforme 0.26% 0.24 Fully adjusted 0.0284 0.0279 3.1E-01 699 0.0608 0.0479 2.1E-01 226 1.8E-01 Fish intake - DDR Eubacterium biforme 0.26% 0.24 Choline intake - DDR 0.0142 0.0287 6.2E-01 699 0.0348 0.0495 4.8E-01 226 2.0E-01 Fish intake - DDR Eubacterium biforme 0.26% 0.24 Choline intake - FFQ 0.0331 0.0286 2.5E-01 699 0.0652 0.0482 1.8E-01 226 1.8E-01 Fish intake - DDR Eubacterium biforme 0.26% 0.24 Dairy intake - DDR 0.0317 0.0279 2.6E-01 699 0.0617 0.0485 2.0E-01 226 1.7E-01 Fish intake - DDR Eubacterium biforme 0.26% 0.24 Dairy intake - FFQ 0.0307 0.0280 2.7E-01 699 0.0660 0.0475 1.7E-01 226 1.9E-01 Fish intake - DDR Eubacterium biforme 0.26% 0.24 Egg intake - DDR 0.0283 0.0279 3.1E-01 699 0.0636 0.0483 1.9E-01 226 1.8E-01 Fish intake - DDR Eubacterium biforme 0.26% 0.24 Egg intake - FFQ 0.0282 0.0280 3.1E-01 699 0.0661 0.0480 1.7E-01 226 1.7E-01 Fish intake - DDR Eubacterium biforme 0.26% 0.24 Eubacterium hallii 0.0235 0.0277 4.0E-01 699 0.0602 0.0477 2.1E-01 226 1.8E-01 Fish intake - DDR Eubacterium biforme 0.26% 0.24 Fish intake - FFQ 0.0179 0.0288 5.4E-01 699 0.0272 0.0519 6.0E-01 226 2.5E-01 Fish intake - DDR Eubacterium biforme 0.26% 0.24 Plasma choline 0.0323 0.0279 2.5E-01 699 0.0536 0.0489 2.7E-01 226 1.5E-01 Fish intake - DDR Eubacterium biforme 0.26% 0.24 Plasma L-carnitine 0.0265 0.0280 3.4E-01 699 0.0937 0.0499 6.1E-02 226 9.5E-02 Fish intake - DDR Eubacterium biforme 0.26% 0.24 Red meat intake - DDR 0.0314 0.0280 2.6E-01 699 0.0516 0.0483 2.9E-01 226 2.3E-01 Fish intake - DDR Eubacterium biforme 0.26% 0.24 Red meat intake - FFQ 0.0262 0.0281 3.5E-01 699 0.0640 0.0485 1.9E-01 226 1.7E-01 Fish intake - DDR Eubacterium biforme 0.26% 0.24 Alistipes shahii 0.0290 0.0280 3.0E-01 699 0.0742 0.0479 1.2E-01 226 1.8E-01 Fish intake - DDR Eubacterium biforme 0.26% 0.24 Clostridiales bacterium 1 7 47FAA 0.0285 0.0277 3.0E-01 699 0.0627 0.0485 2.0E-01 226 2.1E-01 Fish intake - DDR Eubacterium biforme 0.26% 0.24 Clostridium citroniae 0.0268 0.0278 3.3E-01 699 0.0536 0.0479 2.6E-01 226 2.4E-01 Fish intake - DDR Eubacterium biforme 0.26% 0.24 Clostridium clostridioforme 0.0303 0.0274 2.7E-01 699 0.0619 0.0475 1.9E-01 226 1.9E-01 Fish intake - DDR Eubacterium biforme 0.26% 0.24 Clostridium nexile 0.0302 0.0277 2.8E-01 699 0.0537 0.0480 2.6E-01 226 2.3E-01 Fish intake - DDR Eubacterium biforme 0.26% 0.24 Eggerthella (unclassified) 0.0285 0.0279 3.1E-01 699 0.0615 0.0473 2.0E-01 226 1.8E-01 Fish intake - DDR Eubacterium biforme 0.26% 0.24 Erysipelotrichaceae bacterium 21 3 0.0283 0.0279 3.1E-01 699 0.0686 0.0478 1.5E-01 226 1.8E-01 Fish intake - DDR Eubacterium biforme 0.26% 0.24 Roseburia hominis 0.0266 0.0278 3.4E-01 699 0.0786 0.0467 9.4E-02 226 1.2E-01 Red meat intake - FFQ Eubacterium hallii 0.69% 0.92 Fully adjusted -0.1785 0.3409 6.0E-01 65 0.0413 0.0679 5.4E-01 860 6.8E-01 Red meat intake - FFQ Eubacterium hallii 0.69% 0.92 Choline intake - DDR -0.1850 0.3536 6.0E-01 65 0.0283 0.0680 6.8E-01 860 5.9E-01 Red meat intake - FFQ Eubacterium hallii 0.69% 0.92 Choline intake - FFQ -0.3017 0.3585 4.0E-01 65 0.0448 0.0733 5.4E-01 860 6.0E-01 Red meat intake - FFQ Eubacterium hallii 0.69% 0.92 Dairy intake - DDR -0.2096 0.3349 5.3E-01 65 0.0495 0.0679 4.7E-01 860 7.0E-01 Red meat intake - FFQ Eubacterium hallii 0.69% 0.92 Dairy intake - FFQ -0.1971 0.3464 5.7E-01 65 0.0512 0.0677 4.5E-01 860 7.3E-01 Red meat intake - FFQ Eubacterium hallii 0.69% 0.92 Egg intake - DDR -0.1632 0.3456 6.4E-01 65 0.0383 0.0683 5.8E-01 860 6.8E-01 Red meat intake - FFQ Eubacterium hallii 0.69% 0.92 Egg intake - FFQ -0.1826 0.3428 6.0E-01 65 0.0234 0.0683 7.3E-01 860 7.3E-01 Red meat intake - FFQ Eubacterium hallii 0.69% 0.92 Eubacterium biforme -0.1581 0.3499 6.5E-01 65 0.0427 0.0680 5.3E-01 860 6.6E-01 Red meat intake - FFQ Eubacterium hallii 0.69% 0.92 Fish intake - DDR -0.2107 0.3392 5.4E-01 65 0.0438 0.0684 5.2E-01 860 6.0E-01 Red meat intake - FFQ Eubacterium hallii 0.69% 0.92 Fish intake - FFQ -0.1718 0.3374 6.1E-01 65 0.0417 0.0679 5.4E-01 860 6.7E-01 Red meat intake - FFQ Eubacterium hallii 0.69% 0.92 Plasma choline -0.1673 0.3420 6.3E-01 65 0.0423 0.0678 5.3E-01 860 7.0E-01 Red meat intake - FFQ Eubacterium hallii 0.69% 0.92 Plasma L-carnitine -0.1942 0.3432 5.7E-01 65 0.0337 0.0678 6.2E-01 860 7.2E-01 Red meat intake - FFQ Eubacterium hallii 0.69% 0.92 Red meat intake - DDR -0.3711 0.3791 3.3E-01 65 -0.0018 0.0743 9.8E-01 860 5.6E-01 Red meat intake - FFQ Eubacterium hallii 0.69% 0.92 Alistipes shahii -0.1792 0.3444 6.1E-01 65 0.0395 0.0681 5.6E-01 860 6.7E-01 Red meat intake - FFQ Eubacterium hallii 0.69% 0.92 Clostridiales bacterium 1 7 47FAA -0.0447 0.3171 8.9E-01 65 0.0322 0.0677 6.3E-01 860 7.7E-01 Red meat intake - FFQ Eubacterium hallii 0.69% 0.92 Clostridium citroniae 0.0279 0.3560 9.4E-01 65 0.0561 0.0675 4.1E-01 860 7.3E-01 Red meat intake - FFQ Eubacterium hallii 0.69% 0.92 Clostridium clostridioforme -0.1323 0.3446 7.0E-01 65 0.0355 0.0672 6.0E-01 860 9.2E-01 Red meat intake - FFQ Eubacterium hallii 0.69% 0.92 Clostridium nexile -0.1525 0.3437 6.6E-01 65 0.0446 0.0677 5.1E-01 860 5.9E-01 Red meat intake - FFQ Eubacterium hallii 0.69% 0.92 Eggerthella (unclassified) -0.2766 0.3374 4.2E-01 65 0.0481 0.0678 4.8E-01 860 7.1E-01 Red meat intake - FFQ Eubacterium hallii 0.69% 0.92 Erysipelotrichaceae bacterium 21 3 -0.1387 0.3397 6.8E-01 65 0.0407 0.0680 5.5E-01 860 6.8E-01 Red meat intake - FFQ Eubacterium hallii 0.69% 0.92 Roseburia hominis -0.1605 0.3408 6.4E-01 65 0.0441 0.0672 5.1E-01 860 6.5E-01 Red meat intake - DDR Eubacterium hallii 0.69% 0.92 Fully adjusted 0.0825 0.0756 2.8E-01 65 0.0339 0.0188 7.3E-02 860 4.7E-01 Red meat intake - DDR Eubacterium hallii 0.69% 0.92 Choline intake - DDR 0.0892 0.0801 2.7E-01 65 0.0226 0.0201 2.6E-01 860 4.9E-01 Red meat intake - DDR Eubacterium hallii 0.69% 0.92 Choline intake - FFQ 0.0836 0.0766 2.8E-01 65 0.0312 0.0196 1.1E-01 860 4.5E-01 Red meat intake - DDR Eubacterium hallii 0.69% 0.92 Dairy intake - DDR 0.0781 0.0809 3.4E-01 65 0.0349 0.0188 6.4E-02 860 3.8E-01 Red meat intake - DDR Eubacterium hallii 0.69% 0.92 Dairy intake - FFQ 0.0821 0.0788 3.0E-01 65 0.0376 0.0189 4.6E-02 860 4.1E-01 Red meat intake - DDR Eubacterium hallii 0.69% 0.92 Egg intake - DDR 0.0806 0.0772 3.0E-01 65 0.0331 0.0190 8.1E-02 860 4.9E-01 Red meat intake - DDR Eubacterium hallii 0.69% 0.92 Egg intake - FFQ 0.0816 0.0776 3.0E-01 65 0.0334 0.0190 7.8E-02 860 5.0E-01 Red meat intake - DDR Eubacterium hallii 0.69% 0.92 Eubacterium biforme 0.0738 0.0762 3.4E-01 65 0.0344 0.0189 6.9E-02 860 4.7E-01 Red meat intake - DDR Eubacterium hallii 0.69% 0.92 Fish intake - DDR 0.0824 0.0764 2.9E-01 65 0.0338 0.0189 7.4E-02 860 4.7E-01 Red meat intake - DDR Eubacterium hallii 0.69% 0.92 Fish intake - FFQ 0.1029 0.0764 1.8E-01 65 0.0361 0.0189 5.6E-02 860 4.5E-01 Red meat intake - DDR Eubacterium hallii 0.69% 0.92 Plasma choline 0.0691 0.0777 3.8E-01 65 0.0333 0.0188 7.7E-02 860 4.0E-01 Red meat intake - DDR Eubacterium hallii 0.69% 0.92 Plasma L-carnitine 0.0771 0.0799 3.4E-01 65 0.0284 0.0190 1.4E-01 860 4.0E-01 Red meat intake - DDR Eubacterium hallii 0.69% 0.92 Red meat intake - FFQ 0.1145 0.0794 1.6E-01 65 0.0352 0.0204 8.5E-02 860 4.9E-01 Red meat intake - DDR Eubacterium hallii 0.69% 0.92 Alistipes shahii 0.0834 0.0766 2.8E-01 65 0.0340 0.0189 7.1E-02 860 4.8E-01 Red meat intake - DDR Eubacterium hallii 0.69% 0.92 Clostridiales bacterium 1 7 47FAA 0.1252 0.0665 6.6E-02 65 0.0305 0.0188 1.1E-01 860 3.3E-01 Red meat intake - DDR Eubacterium hallii 0.69% 0.92 Clostridium citroniae 0.1281 0.0763 1.0E-01 65 0.0317 0.0187 9.1E-02 860 3.9E-01 Red meat intake - DDR Eubacterium hallii 0.69% 0.92 Clostridium clostridioforme 0.0910 0.0738 2.2E-01 65 0.0355 0.0187 5.7E-02 860 4.0E-01 Red meat intake - DDR Eubacterium hallii 0.69% 0.92 Clostridium nexile 0.0810 0.0759 2.9E-01 65 0.0344 0.0188 6.8E-02 860 5.0E-01 Red meat intake - DDR Eubacterium hallii 0.69% 0.92 Eggerthella (unclassified) 0.0621 0.0803 4.4E-01 65 0.0375 0.0189 4.8E-02 860 4.5E-01 Red meat intake - DDR Eubacterium hallii 0.69% 0.92 Erysipelotrichaceae bacterium 21 3 0.0838 0.0750 2.7E-01 65 0.0339 0.0189 7.2E-02 860 4.8E-01 Red meat intake - DDR Eubacterium hallii 0.69% 0.92 Roseburia hominis 0.0871 0.0759 2.6E-01 65 0.0359 0.0187 5.5E-02 860 4.8E-01 Choline intake - FFQ Eubacterium hallii 0.69% 0.92 Fully adjusted 0.1881 0.2152 3.9E-01 65 0.0844 0.0563 1.3E-01 860 6.6E-01 Choline intake - FFQ Eubacterium hallii 0.69% 0.92 Choline intake - DDR 0.2261 0.2358 3.4E-01 65 0.0534 0.0609 3.8E-01 860 6.9E-01 Choline intake - FFQ Eubacterium hallii 0.69% 0.92 Dairy intake - DDR 0.1759 0.2117 4.1E-01 65 0.0672 0.0572 2.4E-01 860 6.2E-01 Choline intake - FFQ Eubacterium hallii 0.69% 0.92 Dairy intake - FFQ 0.2327 0.2269 3.1E-01 65 0.0498 0.0587 4.0E-01 860 7.4E-01 Choline intake - FFQ Eubacterium hallii 0.69% 0.92 Egg intake - DDR 0.1846 0.2565 4.7E-01 65 0.0894 0.0583 1.3E-01 860 6.6E-01 Choline intake - FFQ Eubacterium hallii 0.69% 0.92 Egg intake - FFQ 0.1694 0.3093 5.9E-01 65 0.0361 0.0645 5.8E-01 860 7.2E-01 Choline intake - FFQ Eubacterium hallii 0.69% 0.92 Eubacterium biforme 0.1886 0.2170 3.9E-01 65 0.0840 0.0563 1.4E-01 860 6.4E-01 Choline intake - FFQ Eubacterium hallii 0.69% 0.92 Fish intake - DDR 0.2113 0.2100 3.2E-01 65 0.1081 0.0557 5.2E-02 860 7.1E-01 Choline intake - FFQ Eubacterium hallii 0.69% 0.92 Fish intake - FFQ 0.1801 0.2107 4.0E-01 65 0.0841 0.0563 1.4E-01 860 6.5E-01 Choline intake - FFQ Eubacterium hallii 0.69% 0.92 Plasma choline 0.1544 0.2213 4.9E-01 65 0.0788 0.0564 1.6E-01 860 6.2E-01 27

Supplementary Data 2a Absence (species)/ Non- Presence (species)/ Stratified by Dietary Exposure Additionally conditioned on producer (mixed score) TMAO-producer (mixed P-interaction Taxa Abundance Prevalence Effect Se P n Effect Se P n Choline intake - FFQ Eubacterium hallii 0.69% 0.92 Plasma L-carnitine 0.1666 0.2204 4.5E-01 65 0.0666 0.0568 2.4E-01 860 6.0E-01 Choline intake - FFQ Eubacterium hallii 0.69% 0.92 Red meat intake - DDR 0.2298 0.2158 2.9E-01 65 0.0671 0.0574 2.4E-01 860 5.4E-01 Choline intake - FFQ Eubacterium hallii 0.69% 0.92 Red meat intake - FFQ 0.2483 0.2274 2.8E-01 65 0.0721 0.0587 2.2E-01 860 6.3E-01 Choline intake - FFQ Eubacterium hallii 0.69% 0.92 Alistipes shahii 0.1913 0.2185 3.9E-01 65 0.0872 0.0565 1.2E-01 860 7.1E-01 Choline intake - FFQ Eubacterium hallii 0.69% 0.92 Clostridiales bacterium 1 7 47FAA 0.1705 0.1980 3.9E-01 65 0.0888 0.0562 1.1E-01 860 6.7E-01 Choline intake - FFQ Eubacterium hallii 0.69% 0.92 Clostridium citroniae 0.1504 0.2125 4.8E-01 65 0.0866 0.0559 1.2E-01 860 8.6E-01 Choline intake - FFQ Eubacterium hallii 0.69% 0.92 Clostridium clostridioforme 0.2557 0.2203 2.5E-01 65 0.0793 0.0557 1.6E-01 860 2.1E-01 Choline intake - FFQ Eubacterium hallii 0.69% 0.92 Clostridium nexile 0.1878 0.2158 3.9E-01 65 0.0781 0.0562 1.7E-01 860 9.0E-01 Choline intake - FFQ Eubacterium hallii 0.69% 0.92 Eggerthella (unclassified) 0.1403 0.2139 5.1E-01 65 0.0807 0.0562 1.5E-01 860 6.2E-01 Choline intake - FFQ Eubacterium hallii 0.69% 0.92 Erysipelotrichaceae bacterium 21 3 0.0884 0.2323 7.1E-01 65 0.0844 0.0563 1.3E-01 860 8.5E-01 Choline intake - FFQ Eubacterium hallii 0.69% 0.92 Roseburia hominis 0.2107 0.2152 3.3E-01 65 0.0863 0.0557 1.2E-01 860 6.4E-01 Choline intake - DDR Eubacterium hallii 0.69% 0.92 Fully adjusted 0.0454 0.1897 8.1E-01 65 0.0877 0.0424 3.9E-02 860 7.6E-01 Choline intake - DDR Eubacterium hallii 0.69% 0.92 Choline intake - FFQ 0.0839 0.2124 6.9E-01 65 0.0604 0.0460 1.9E-01 860 7.9E-01 Choline intake - DDR Eubacterium hallii 0.69% 0.92 Dairy intake - DDR 0.0197 0.1908 9.2E-01 65 0.0798 0.0425 6.1E-02 860 8.3E-01 Choline intake - DDR Eubacterium hallii 0.69% 0.92 Dairy intake - FFQ 0.0732 0.1953 7.1E-01 65 0.0738 0.0430 8.7E-02 860 7.7E-01 Choline intake - DDR Eubacterium hallii 0.69% 0.92 Egg intake - DDR 0.0969 0.2862 7.4E-01 65 0.1341 0.0559 1.7E-02 860 7.8E-01 Choline intake - DDR Eubacterium hallii 0.69% 0.92 Egg intake - FFQ 0.0546 0.2088 7.9E-01 65 0.0732 0.0446 1.0E-01 860 7.7E-01 Choline intake - DDR Eubacterium hallii 0.69% 0.92 Eubacterium biforme 0.0446 0.1910 8.2E-01 65 0.0873 0.0425 4.0E-02 860 7.8E-01 Choline intake - DDR Eubacterium hallii 0.69% 0.92 Fish intake - DDR 0.0397 0.1908 8.4E-01 65 0.0952 0.0428 2.6E-02 860 7.2E-01 Choline intake - DDR Eubacterium hallii 0.69% 0.92 Fish intake - FFQ 0.0274 0.1907 8.9E-01 65 0.0865 0.0424 4.1E-02 860 7.4E-01 Choline intake - DDR Eubacterium hallii 0.69% 0.92 Plasma choline 0.0365 0.1905 8.5E-01 65 0.0844 0.0424 4.7E-02 860 8.2E-01 Choline intake - DDR Eubacterium hallii 0.69% 0.92 Plasma L-carnitine 0.0257 0.1934 8.9E-01 65 0.0791 0.0425 6.3E-02 860 8.7E-01 Choline intake - DDR Eubacterium hallii 0.69% 0.92 Red meat intake - DDR -0.0532 0.1953 7.9E-01 65 0.0729 0.0453 1.1E-01 860 5.2E-01 Choline intake - DDR Eubacterium hallii 0.69% 0.92 Red meat intake - FFQ 0.0702 0.1924 7.2E-01 65 0.0872 0.0430 4.3E-02 860 7.9E-01 Choline intake - DDR Eubacterium hallii 0.69% 0.92 Alistipes shahii 0.0453 0.1916 8.1E-01 65 0.0900 0.0425 3.5E-02 860 7.4E-01 Choline intake - DDR Eubacterium hallii 0.69% 0.92 Clostridiales bacterium 1 7 47FAA 0.0195 0.1711 9.1E-01 65 0.0846 0.0423 4.6E-02 860 8.0E-01 Choline intake - DDR Eubacterium hallii 0.69% 0.92 Clostridium citroniae 0.0722 0.1887 7.0E-01 65 0.0829 0.0422 5.0E-02 860 7.7E-01 Choline intake - DDR Eubacterium hallii 0.69% 0.92 Clostridium clostridioforme 0.0477 0.1863 8.0E-01 65 0.0829 0.0420 4.9E-02 860 9.8E-01 Choline intake - DDR Eubacterium hallii 0.69% 0.92 Clostridium nexile 0.0400 0.1902 8.3E-01 65 0.0895 0.0423 3.5E-02 860 5.6E-01 Choline intake - DDR Eubacterium hallii 0.69% 0.92 Eggerthella (unclassified) 0.0453 0.1890 8.1E-01 65 0.0883 0.0424 3.8E-02 860 7.8E-01 Choline intake - DDR Eubacterium hallii 0.69% 0.92 Erysipelotrichaceae bacterium 21 3 0.0202 0.1906 9.2E-01 65 0.0878 0.0425 3.9E-02 860 6.8E-01 Choline intake - DDR Eubacterium hallii 0.69% 0.92 Roseburia hominis 0.0450 0.1901 8.1E-01 65 0.0967 0.0421 2.2E-02 860 7.3E-01 Plasma choline Eubacterium hallii 0.69% 0.92 Fully adjusted -0.0958 0.1075 3.8E-01 65 0.0570 0.0358 1.1E-01 860 1.9E-01 Plasma choline Eubacterium hallii 0.69% 0.92 Choline intake - DDR -0.0966 0.1088 3.8E-01 65 0.0521 0.0358 1.5E-01 860 2.3E-01 Plasma choline Eubacterium hallii 0.69% 0.92 Choline intake - FFQ -0.0794 0.1105 4.8E-01 65 0.0556 0.0363 1.3E-01 860 2.5E-01 Plasma choline Eubacterium hallii 0.69% 0.92 Dairy intake - DDR -0.0909 0.1056 3.9E-01 65 0.0525 0.0358 1.4E-01 860 2.0E-01 Plasma choline Eubacterium hallii 0.69% 0.92 Dairy intake - FFQ -0.1033 0.1093 3.5E-01 65 0.0548 0.0357 1.2E-01 860 2.2E-01 Plasma choline Eubacterium hallii 0.69% 0.92 Egg intake - DDR -0.0883 0.1156 4.5E-01 65 0.0565 0.0360 1.2E-01 860 2.2E-01 Plasma choline Eubacterium hallii 0.69% 0.92 Egg intake - FFQ -0.0801 0.1153 4.9E-01 65 0.0511 0.0359 1.5E-01 860 2.9E-01 Plasma choline Eubacterium hallii 0.69% 0.92 Eubacterium biforme -0.0926 0.1179 4.4E-01 65 0.0566 0.0358 1.1E-01 860 1.8E-01 Plasma choline Eubacterium hallii 0.69% 0.92 Fish intake - DDR -0.0909 0.1083 4.1E-01 65 0.0538 0.0354 1.3E-01 860 2.3E-01 Plasma choline Eubacterium hallii 0.69% 0.92 Fish intake - FFQ -0.0896 0.1068 4.1E-01 65 0.0558 0.0358 1.2E-01 860 2.0E-01 Plasma choline Eubacterium hallii 0.69% 0.92 Plasma L-carnitine -0.0782 0.1253 5.4E-01 65 0.0402 0.0367 2.7E-01 860 2.0E-01 Plasma choline Eubacterium hallii 0.69% 0.92 Red meat intake - DDR -0.0960 0.1096 3.9E-01 65 0.0527 0.0358 1.4E-01 860 2.2E-01 Plasma choline Eubacterium hallii 0.69% 0.92 Red meat intake - FFQ -0.0937 0.1084 3.9E-01 65 0.0612 0.0359 8.9E-02 860 1.8E-01 Plasma choline Eubacterium hallii 0.69% 0.92 Alistipes shahii -0.0957 0.1087 3.8E-01 65 0.0582 0.0359 1.0E-01 860 1.8E-01 Plasma choline Eubacterium hallii 0.69% 0.92 Clostridiales bacterium 1 7 47FAA -0.1030 0.0985 3.0E-01 65 0.0562 0.0357 1.2E-01 860 2.0E-01 Plasma choline Eubacterium hallii 0.69% 0.92 Clostridium citroniae -0.0877 0.1054 4.1E-01 65 0.0498 0.0356 1.6E-01 860 2.3E-01 Plasma choline Eubacterium hallii 0.69% 0.92 Clostridium clostridioforme -0.0928 0.1075 3.9E-01 65 0.0655 0.0355 6.5E-02 860 2.4E-01 Plasma choline Eubacterium hallii 0.69% 0.92 Clostridium nexile -0.0854 0.1089 4.4E-01 65 0.0671 0.0359 6.2E-02 860 1.5E-01 Plasma choline Eubacterium hallii 0.69% 0.92 Eggerthella (unclassified) -0.0275 0.1156 8.1E-01 65 0.0574 0.0357 1.1E-01 860 1.7E-01 Plasma choline Eubacterium hallii 0.69% 0.92 Erysipelotrichaceae bacterium 21 3 -0.0988 0.1065 3.6E-01 65 0.0572 0.0358 1.1E-01 860 2.1E-01 Plasma choline Eubacterium hallii 0.69% 0.92 Roseburia hominis -0.0841 0.1080 4.4E-01 65 0.0665 0.0355 6.1E-02 860 1.9E-01 Plasma L-carnitine Eubacterium hallii 0.69% 0.92 Fully adjusted -0.1323 0.1921 4.9E-01 65 0.0752 0.0324 2.1E-02 860 3.9E-01 Plasma L-carnitine Eubacterium hallii 0.69% 0.92 Choline intake - DDR -0.1439 0.2008 4.8E-01 65 0.0686 0.0326 3.6E-02 860 4.7E-01 Plasma L-carnitine Eubacterium hallii 0.69% 0.92 Choline intake - FFQ -0.1054 0.1962 5.9E-01 65 0.0712 0.0333 3.3E-02 860 4.3E-01 Plasma L-carnitine Eubacterium hallii 0.69% 0.92 Dairy intake - DDR -0.0655 0.1940 7.4E-01 65 0.0680 0.0327 3.8E-02 860 3.9E-01 Plasma L-carnitine Eubacterium hallii 0.69% 0.92 Dairy intake - FFQ -0.1229 0.1987 5.4E-01 65 0.0702 0.0324 3.1E-02 860 3.4E-01 Plasma L-carnitine Eubacterium hallii 0.69% 0.92 Egg intake - DDR -0.1154 0.2018 5.7E-01 65 0.0748 0.0325 2.2E-02 860 4.1E-01 Plasma L-carnitine Eubacterium hallii 0.69% 0.92 Egg intake - FFQ -0.0985 0.2069 6.4E-01 65 0.0694 0.0326 3.4E-02 860 4.1E-01 Plasma L-carnitine Eubacterium hallii 0.69% 0.92 Eubacterium biforme -0.1205 0.1993 5.5E-01 65 0.0763 0.0325 1.9E-02 860 3.5E-01 Plasma L-carnitine Eubacterium hallii 0.69% 0.92 Fish intake - DDR -0.1383 0.1964 4.8E-01 65 0.0737 0.0322 2.2E-02 860 4.2E-01 Plasma L-carnitine Eubacterium hallii 0.69% 0.92 Fish intake - FFQ -0.1212 0.1889 5.2E-01 65 0.0748 0.0325 2.1E-02 860 3.6E-01 Plasma L-carnitine Eubacterium hallii 0.69% 0.92 Plasma choline -0.0624 0.2234 7.8E-01 65 0.0669 0.0333 4.5E-02 860 3.7E-01 Plasma L-carnitine Eubacterium hallii 0.69% 0.92 Red meat intake - DDR -0.0625 0.2060 7.6E-01 65 0.0669 0.0328 4.2E-02 860 6.0E-01 Plasma L-carnitine Eubacterium hallii 0.69% 0.92 Red meat intake - FFQ -0.1393 0.1938 4.8E-01 65 0.0745 0.0325 2.2E-02 860 4.0E-01 Plasma L-carnitine Eubacterium hallii 0.69% 0.92 Alistipes shahii -0.1339 0.1946 4.9E-01 65 0.0749 0.0325 2.1E-02 860 3.8E-01 Plasma L-carnitine Eubacterium hallii 0.69% 0.92 Clostridiales bacterium 1 7 47FAA -0.3196 0.1795 8.1E-02 65 0.0769 0.0323 1.8E-02 860 2.1E-01 Plasma L-carnitine Eubacterium hallii 0.69% 0.92 Clostridium citroniae -0.1622 0.1883 3.9E-01 65 0.0764 0.0322 1.8E-02 860 3.0E-01 Plasma L-carnitine Eubacterium hallii 0.69% 0.92 Clostridium clostridioforme -0.2348 0.2044 2.6E-01 65 0.0788 0.0321 1.4E-02 860 1.4E-01 Plasma L-carnitine Eubacterium hallii 0.69% 0.92 Clostridium nexile -0.1356 0.1927 4.8E-01 65 0.0806 0.0324 1.3E-02 860 7.2E-01 Plasma L-carnitine Eubacterium hallii 0.69% 0.92 Eggerthella (unclassified) 0.0648 0.2255 7.7E-01 65 0.0806 0.0325 1.3E-02 860 3.5E-01 Plasma L-carnitine Eubacterium hallii 0.69% 0.92 Erysipelotrichaceae bacterium 21 3 -0.0621 0.1996 7.6E-01 65 0.0756 0.0325 2.0E-02 860 3.7E-01 Plasma L-carnitine Eubacterium hallii 0.69% 0.92 Roseburia hominis -0.0737 0.2024 7.2E-01 65 0.0869 0.0322 7.1E-03 860 4.4E-01 Dairy intake - FFQ Eubacterium hallii 0.69% 0.92 Fully adjusted -0.0406 0.1118 7.2E-01 65 0.0696 0.0273 1.1E-02 860 5.5E-01 Dairy intake - FFQ Eubacterium hallii 0.69% 0.92 Choline intake - DDR -0.0406 0.1135 7.2E-01 65 0.0611 0.0278 2.8E-02 860 5.3E-01 Dairy intake - FFQ Eubacterium hallii 0.69% 0.92 Choline intake - FFQ -0.0767 0.1171 5.2E-01 65 0.0602 0.0294 4.1E-02 860 5.5E-01 Dairy intake - FFQ Eubacterium hallii 0.69% 0.92 Dairy intake - DDR 0.0786 0.1286 5.4E-01 65 0.0578 0.0330 8.0E-02 860 5.4E-01 Dairy intake - FFQ Eubacterium hallii 0.69% 0.92 Egg intake - DDR -0.0567 0.1159 6.3E-01 65 0.0696 0.0273 1.1E-02 860 5.2E-01 Dairy intake - FFQ Eubacterium hallii 0.69% 0.92 Egg intake - FFQ -0.0520 0.1134 6.5E-01 65 0.0666 0.0273 1.5E-02 860 5.3E-01 28

Supplementary Data 2a Absence (species)/ Non- Presence (species)/ Stratified by Dietary Exposure Additionally conditioned on producer (mixed score) TMAO-producer (mixed P-interaction Taxa Abundance Prevalence Effect Se P n Effect Se P n Dairy intake - FFQ Eubacterium hallii 0.69% 0.92 Eubacterium biforme -0.0554 0.1162 6.4E-01 65 0.0692 0.0274 1.2E-02 860 5.8E-01 Dairy intake - FFQ Eubacterium hallii 0.69% 0.92 Fish intake - DDR -0.0045 0.1060 9.7E-01 65 0.0625 0.0273 2.2E-02 860 6.3E-01 Dairy intake - FFQ Eubacterium hallii 0.69% 0.92 Fish intake - FFQ -0.0340 0.1071 7.5E-01 65 0.0709 0.0273 9.5E-03 860 5.6E-01 Dairy intake - FFQ Eubacterium hallii 0.69% 0.92 Plasma choline -0.0555 0.1130 6.3E-01 65 0.0686 0.0272 1.2E-02 860 5.9E-01 Dairy intake - FFQ Eubacterium hallii 0.69% 0.92 Plasma L-carnitine -0.0251 0.1152 8.3E-01 65 0.0658 0.0272 1.6E-02 860 5.6E-01 Dairy intake - FFQ Eubacterium hallii 0.69% 0.92 Red meat intake - DDR -0.0056 0.1146 9.6E-01 65 0.0688 0.0272 1.2E-02 860 6.7E-01 Dairy intake - FFQ Eubacterium hallii 0.69% 0.92 Red meat intake - FFQ -0.0487 0.1134 6.7E-01 65 0.0765 0.0275 5.5E-03 860 5.5E-01 Dairy intake - FFQ Eubacterium hallii 0.69% 0.92 Alistipes shahii -0.0406 0.1129 7.2E-01 65 0.0699 0.0273 1.1E-02 860 5.3E-01 Dairy intake - FFQ Eubacterium hallii 0.69% 0.92 Clostridiales bacterium 1 7 47FAA 0.0015 0.1038 9.9E-01 65 0.0706 0.0272 9.5E-03 860 5.8E-01 Dairy intake - FFQ Eubacterium hallii 0.69% 0.92 Clostridium citroniae -0.0103 0.1110 9.3E-01 65 0.0718 0.0270 8.1E-03 860 5.0E-01 Dairy intake - FFQ Eubacterium hallii 0.69% 0.92 Clostridium clostridioforme -0.0410 0.1117 7.2E-01 65 0.0608 0.0271 2.5E-02 860 6.7E-01 Dairy intake - FFQ Eubacterium hallii 0.69% 0.92 Clostridium nexile -0.0409 0.1121 7.2E-01 65 0.0681 0.0272 1.3E-02 860 2.5E-01 Dairy intake - FFQ Eubacterium hallii 0.69% 0.92 Eggerthella (unclassified) 0.0008 0.1125 9.9E-01 65 0.0669 0.0272 1.4E-02 860 5.4E-01 Dairy intake - FFQ Eubacterium hallii 0.69% 0.92 Erysipelotrichaceae bacterium 21 3 -0.0136 0.1128 9.0E-01 65 0.0696 0.0273 1.1E-02 860 5.5E-01 Dairy intake - FFQ Eubacterium hallii 0.69% 0.92 Roseburia hominis -0.0359 0.1117 7.5E-01 65 0.0745 0.0270 5.9E-03 860 5.3E-01 Dairy intake - DDR Eubacterium hallii 0.69% 0.92 Fully adjusted -0.0953 0.0851 2.7E-01 65 0.0624 0.0273 2.2E-02 860 4.8E-02 Dairy intake - DDR Eubacterium hallii 0.69% 0.92 Choline intake - DDR -0.0942 0.0866 2.8E-01 65 0.0579 0.0273 3.4E-02 860 6.4E-02 Dairy intake - DDR Eubacterium hallii 0.69% 0.92 Choline intake - FFQ -0.0961 0.0859 2.7E-01 65 0.0604 0.0280 3.1E-02 860 5.3E-02 Dairy intake - DDR Eubacterium hallii 0.69% 0.92 Dairy intake - FFQ -0.0928 0.0994 3.6E-01 65 0.0431 0.0317 1.7E-01 860 6.2E-02 Dairy intake - DDR Eubacterium hallii 0.69% 0.92 Egg intake - DDR -0.0976 0.0871 2.7E-01 65 0.0639 0.0274 2.0E-02 860 5.0E-02 Dairy intake - DDR Eubacterium hallii 0.69% 0.92 Egg intake - FFQ -0.0973 0.0868 2.7E-01 65 0.0638 0.0273 2.0E-02 860 6.0E-02 Dairy intake - DDR Eubacterium hallii 0.69% 0.92 Eubacterium biforme -0.1134 0.0879 2.0E-01 65 0.0621 0.0273 2.3E-02 860 5.1E-02 Dairy intake - DDR Eubacterium hallii 0.69% 0.92 Fish intake - DDR -0.0878 0.0869 3.2E-01 65 0.0594 0.0274 3.0E-02 860 5.0E-02 Dairy intake - DDR Eubacterium hallii 0.69% 0.92 Fish intake - FFQ -0.1111 0.0858 2.0E-01 65 0.0591 0.0273 3.1E-02 860 4.8E-02 Dairy intake - DDR Eubacterium hallii 0.69% 0.92 Plasma choline -0.0935 0.0854 2.8E-01 65 0.0615 0.0272 2.4E-02 860 5.2E-02 Dairy intake - DDR Eubacterium hallii 0.69% 0.92 Plasma L-carnitine -0.0880 0.0872 3.2E-01 65 0.0559 0.0274 4.1E-02 860 5.5E-02 Dairy intake - DDR Eubacterium hallii 0.69% 0.92 Red meat intake - DDR -0.0155 0.0955 8.7E-01 65 0.0628 0.0272 2.1E-02 860 1.1E-01 Dairy intake - DDR Eubacterium hallii 0.69% 0.92 Red meat intake - FFQ -0.1085 0.0861 2.1E-01 65 0.0665 0.0274 1.5E-02 860 4.6E-02 Dairy intake - DDR Eubacterium hallii 0.69% 0.92 Alistipes shahii -0.0953 0.0861 2.7E-01 65 0.0639 0.0273 1.9E-02 860 4.5E-02 Dairy intake - DDR Eubacterium hallii 0.69% 0.92 Clostridiales bacterium 1 7 47FAA -0.1006 0.0763 1.9E-01 65 0.0657 0.0272 1.6E-02 860 5.1E-02 Dairy intake - DDR Eubacterium hallii 0.69% 0.92 Clostridium citroniae -0.0844 0.0850 3.3E-01 65 0.0689 0.0271 1.1E-02 860 5.4E-02 Dairy intake - DDR Eubacterium hallii 0.69% 0.92 Clostridium clostridioforme -0.1537 0.0862 8.1E-02 65 0.0571 0.0270 3.5E-02 860 7.1E-03 Dairy intake - DDR Eubacterium hallii 0.69% 0.92 Clostridium nexile -0.0975 0.0853 2.6E-01 65 0.0614 0.0272 2.4E-02 860 9.9E-02 Dairy intake - DDR Eubacterium hallii 0.69% 0.92 Eggerthella (unclassified) -0.0607 0.0979 5.4E-01 65 0.0644 0.0272 1.8E-02 860 3.9E-02 Dairy intake - DDR Eubacterium hallii 0.69% 0.92 Erysipelotrichaceae bacterium 21 3 -0.0916 0.0850 2.9E-01 65 0.0624 0.0274 2.3E-02 860 4.9E-02 Dairy intake - DDR Eubacterium hallii 0.69% 0.92 Roseburia hominis -0.1004 0.0854 2.5E-01 65 0.0682 0.0270 1.2E-02 860 3.3E-02 Egg intake - FFQ Eubacterium hallii 0.69% 0.92 Fully adjusted 0.2120 0.3118 5.0E-01 65 0.1653 0.0858 5.5E-02 860 9.2E-01 Egg intake - FFQ Eubacterium hallii 0.69% 0.92 Choline intake - DDR 0.2449 0.3348 4.7E-01 65 0.1281 0.0890 1.5E-01 860 9.2E-01 Egg intake - FFQ Eubacterium hallii 0.69% 0.92 Choline intake - FFQ 0.0380 0.4467 9.3E-01 65 0.1555 0.1014 1.3E-01 860 9.9E-01 Egg intake - FFQ Eubacterium hallii 0.69% 0.92 Dairy intake - DDR 0.1546 0.3089 6.2E-01 65 0.1594 0.0858 6.3E-02 860 8.7E-01 Egg intake - FFQ Eubacterium hallii 0.69% 0.92 Dairy intake - FFQ 0.2320 0.3173 4.7E-01 65 0.1523 0.0858 7.6E-02 860 9.9E-01 Egg intake - FFQ Eubacterium hallii 0.69% 0.92 Egg intake - DDR 0.1817 0.3609 6.2E-01 65 0.1916 0.0967 4.8E-02 860 9.3E-01 Egg intake - FFQ Eubacterium hallii 0.69% 0.92 Eubacterium biforme 0.1987 0.3173 5.3E-01 65 0.1642 0.0860 5.7E-02 860 9.1E-01 Egg intake - FFQ Eubacterium hallii 0.69% 0.92 Fish intake - DDR 0.1348 0.3158 6.7E-01 65 0.1419 0.0860 9.9E-02 860 9.6E-01 Egg intake - FFQ Eubacterium hallii 0.69% 0.92 Fish intake - FFQ 0.2612 0.3121 4.1E-01 65 0.1663 0.0859 5.3E-02 860 9.0E-01 Egg intake - FFQ Eubacterium hallii 0.69% 0.92 Plasma choline 0.1330 0.3334 6.9E-01 65 0.1541 0.0862 7.4E-02 860 8.0E-01 Egg intake - FFQ Eubacterium hallii 0.69% 0.92 Plasma L-carnitine 0.1558 0.3357 6.4E-01 65 0.1459 0.0862 9.1E-02 860 8.6E-01 Egg intake - FFQ Eubacterium hallii 0.69% 0.92 Red meat intake - DDR 0.2306 0.3141 4.7E-01 65 0.1509 0.0862 8.1E-02 860 8.4E-01 Egg intake - FFQ Eubacterium hallii 0.69% 0.92 Red meat intake - FFQ 0.2149 0.3141 5.0E-01 65 0.1733 0.0869 4.7E-02 860 9.3E-01 Egg intake - FFQ Eubacterium hallii 0.69% 0.92 Alistipes shahii 0.2133 0.3152 5.0E-01 65 0.1645 0.0859 5.6E-02 860 9.5E-01 Egg intake - FFQ Eubacterium hallii 0.69% 0.92 Clostridiales bacterium 1 7 47FAA 0.2017 0.2867 4.8E-01 65 0.1645 0.0856 5.5E-02 860 9.3E-01 Egg intake - FFQ Eubacterium hallii 0.69% 0.92 Clostridium citroniae 0.0831 0.3162 7.9E-01 65 0.1552 0.0853 6.9E-02 860 8.4E-01 Egg intake - FFQ Eubacterium hallii 0.69% 0.92 Clostridium clostridioforme 0.2664 0.3145 4.0E-01 65 0.1653 0.0850 5.2E-02 860 6.4E-01 Egg intake - FFQ Eubacterium hallii 0.69% 0.92 Clostridium nexile 0.1988 0.3133 5.3E-01 65 0.1602 0.0857 6.2E-02 860 8.7E-01 Egg intake - FFQ Eubacterium hallii 0.69% 0.92 Eggerthella (unclassified) 0.1338 0.3104 6.7E-01 65 0.1589 0.0858 6.4E-02 860 8.8E-01 Egg intake - FFQ Eubacterium hallii 0.69% 0.92 Erysipelotrichaceae bacterium 21 3 0.0214 0.3493 9.5E-01 65 0.1663 0.0860 5.3E-02 860 6.6E-01 Egg intake - FFQ Eubacterium hallii 0.69% 0.92 Roseburia hominis 0.1991 0.3116 5.3E-01 65 0.1681 0.0850 4.8E-02 860 9.2E-01 Egg intake - DDR Eubacterium hallii 0.69% 0.92 Fully adjusted 0.0045 0.3101 9.9E-01 65 0.0273 0.0645 6.7E-01 860 6.4E-01 Egg intake - DDR Eubacterium hallii 0.69% 0.92 Choline intake - DDR -0.1132 0.4678 8.1E-01 65 -0.1018 0.0839 2.3E-01 860 7.3E-01 Egg intake - DDR Eubacterium hallii 0.69% 0.92 Choline intake - FFQ 0.0684 0.3686 8.5E-01 65 -0.0264 0.0687 7.0E-01 860 6.7E-01 Egg intake - DDR Eubacterium hallii 0.69% 0.92 Dairy intake - DDR -0.0515 0.3134 8.7E-01 65 0.0397 0.0646 5.4E-01 860 6.0E-01 Egg intake - DDR Eubacterium hallii 0.69% 0.92 Dairy intake - FFQ 0.0705 0.3290 8.3E-01 65 0.0207 0.0645 7.5E-01 860 7.7E-01 Egg intake - DDR Eubacterium hallii 0.69% 0.92 Egg intake - FFQ 0.0068 0.3484 9.8E-01 65 -0.0360 0.0730 6.2E-01 860 6.6E-01 Egg intake - DDR Eubacterium hallii 0.69% 0.92 Eubacterium biforme -0.0418 0.3226 9.0E-01 65 0.0265 0.0646 6.8E-01 860 6.3E-01 Egg intake - DDR Eubacterium hallii 0.69% 0.92 Fish intake - DDR 0.0123 0.3119 9.7E-01 65 0.0325 0.0648 6.2E-01 860 6.6E-01 Egg intake - DDR Eubacterium hallii 0.69% 0.92 Fish intake - FFQ -0.0344 0.3126 9.1E-01 65 0.0167 0.0645 8.0E-01 860 6.5E-01 Egg intake - DDR Eubacterium hallii 0.69% 0.92 Plasma choline -0.0947 0.3292 7.7E-01 65 0.0199 0.0646 7.6E-01 860 5.2E-01 Egg intake - DDR Eubacterium hallii 0.69% 0.92 Plasma L-carnitine -0.0444 0.3203 8.9E-01 65 0.0213 0.0644 7.4E-01 860 5.9E-01 Egg intake - DDR Eubacterium hallii 0.69% 0.92 Red meat intake - DDR 0.0524 0.3105 8.7E-01 65 0.0269 0.0653 6.8E-01 860 5.9E-01 Egg intake - DDR Eubacterium hallii 0.69% 0.92 Red meat intake - FFQ -0.0011 0.3113 1.0E+00 65 0.0207 0.0654 7.5E-01 860 6.3E-01 Egg intake - DDR Eubacterium hallii 0.69% 0.92 Alistipes shahii 0.0039 0.3134 9.9E-01 65 0.0285 0.0646 6.6E-01 860 6.6E-01 Egg intake - DDR Eubacterium hallii 0.69% 0.92 Clostridiales bacterium 1 7 47FAA -0.0173 0.2794 9.5E-01 65 0.0293 0.0643 6.5E-01 860 6.6E-01 Egg intake - DDR Eubacterium hallii 0.69% 0.92 Clostridium citroniae -0.0266 0.3081 9.3E-01 65 0.0323 0.0641 6.1E-01 860 7.8E-01 Egg intake - DDR Eubacterium hallii 0.69% 0.92 Clostridium clostridioforme 0.0195 0.3047 9.5E-01 65 0.0238 0.0639 7.1E-01 860 4.0E-01 Egg intake - DDR Eubacterium hallii 0.69% 0.92 Clostridium nexile 0.0072 0.3109 9.8E-01 65 0.0290 0.0644 6.5E-01 860 7.4E-01 Egg intake - DDR Eubacterium hallii 0.69% 0.92 Eggerthella (unclassified) -0.0489 0.3122 8.8E-01 65 0.0290 0.0645 6.5E-01 860 6.1E-01 Egg intake - DDR Eubacterium hallii 0.69% 0.92 Erysipelotrichaceae bacterium 21 3 -0.0210 0.3101 9.5E-01 65 0.0276 0.0646 6.7E-01 860 7.6E-01 Egg intake - DDR Eubacterium hallii 0.69% 0.92 Roseburia hominis 0.0202 0.3114 9.5E-01 65 0.0374 0.0640 5.6E-01 860 6.6E-01 Fish intake - FFQ Eubacterium hallii 0.69% 0.92 Fully adjusted 0.8665 0.6446 1.8E-01 65 0.4449 0.1341 9.5E-04 860 9.9E-01 Fish intake - FFQ Eubacterium hallii 0.69% 0.92 Choline intake - DDR 0.8900 0.6690 1.9E-01 65 0.4496 0.1339 8.2E-04 860 9.8E-01 29

Supplementary Data 2a Absence (species)/ Non- Presence (species)/ Stratified by Dietary Exposure Additionally conditioned on producer (mixed score) TMAO-producer (mixed P-interaction Taxa Abundance Prevalence Effect Se P n Effect Se P n Fish intake - FFQ Eubacterium hallii 0.69% 0.92 Choline intake - FFQ 0.7585 0.6585 2.5E-01 65 0.4488 0.1424 1.7E-03 860 9.5E-01 Fish intake - FFQ Eubacterium hallii 0.69% 0.92 Dairy intake - DDR 1.0719 0.6444 1.0E-01 65 0.4490 0.1339 8.3E-04 860 9.8E-01 Fish intake - FFQ Eubacterium hallii 0.69% 0.92 Dairy intake - FFQ 0.9118 0.6657 1.8E-01 65 0.4780 0.1342 3.9E-04 860 8.9E-01 Fish intake - FFQ Eubacterium hallii 0.69% 0.92 Egg intake - DDR 0.8234 0.6590 2.2E-01 65 0.4444 0.1343 9.7E-04 860 9.9E-01 Fish intake - FFQ Eubacterium hallii 0.69% 0.92 Egg intake - FFQ 0.9742 0.6591 1.5E-01 65 0.4645 0.1343 5.7E-04 860 9.3E-01 Fish intake - FFQ Eubacterium hallii 0.69% 0.92 Eubacterium biforme 0.7882 0.6785 2.5E-01 65 0.4480 0.1343 8.9E-04 860 9.6E-01 Fish intake - FFQ Eubacterium hallii 0.69% 0.92 Fish intake - DDR 0.7883 0.6769 2.5E-01 65 0.4061 0.1406 4.0E-03 860 1.0E+00 Fish intake - FFQ Eubacterium hallii 0.69% 0.92 Plasma choline 0.8350 0.6475 2.0E-01 65 0.4712 0.1350 5.1E-04 860 9.5E-01 Fish intake - FFQ Eubacterium hallii 0.69% 0.92 Plasma L-carnitine 0.7729 0.6645 2.5E-01 65 0.4559 0.1338 6.9E-04 860 9.8E-01 Fish intake - FFQ Eubacterium hallii 0.69% 0.92 Red meat intake - DDR 0.8510 0.6483 2.0E-01 65 0.4479 0.1342 8.9E-04 860 9.4E-01 Fish intake - FFQ Eubacterium hallii 0.69% 0.92 Red meat intake - FFQ 0.8326 0.6526 2.1E-01 65 0.4598 0.1345 6.6E-04 860 9.9E-01 Fish intake - FFQ Eubacterium hallii 0.69% 0.92 Alistipes shahii 0.8684 0.6535 1.9E-01 65 0.4426 0.1342 1.0E-03 860 9.9E-01 Fish intake - FFQ Eubacterium hallii 0.69% 0.92 Clostridiales bacterium 1 7 47FAA 0.2257 0.6347 7.2E-01 65 0.4512 0.1337 7.7E-04 860 7.9E-01 Fish intake - FFQ Eubacterium hallii 0.69% 0.92 Clostridium citroniae 0.5434 0.6670 4.2E-01 65 0.4360 0.1331 1.1E-03 860 8.5E-01 Fish intake - FFQ Eubacterium hallii 0.69% 0.92 Clostridium clostridioforme 0.8564 0.6440 1.9E-01 65 0.4367 0.1327 1.0E-03 860 7.1E-01 Fish intake - FFQ Eubacterium hallii 0.69% 0.92 Clostridium nexile 0.8979 0.6470 1.7E-01 65 0.4534 0.1338 7.4E-04 860 9.0E-01 Fish intake - FFQ Eubacterium hallii 0.69% 0.92 Eggerthella (unclassified) 1.0005 0.6368 1.2E-01 65 0.4659 0.1342 5.4E-04 860 1.0E+00 Fish intake - FFQ Eubacterium hallii 0.69% 0.92 Erysipelotrichaceae bacterium 21 3 1.1192 0.6577 9.5E-02 65 0.4453 0.1342 9.5E-04 860 7.7E-01 Fish intake - FFQ Eubacterium hallii 0.69% 0.92 Roseburia hominis 0.8773 0.6418 1.8E-01 65 0.4595 0.1328 5.7E-04 860 9.5E-01 Fish intake - DDR Eubacterium hallii 0.69% 0.92 Fully adjusted 0.1100 0.1069 3.1E-01 65 0.0526 0.0249 3.5E-02 860 6.1E-01 Fish intake - DDR Eubacterium hallii 0.69% 0.92 Choline intake - DDR 0.0992 0.1242 4.3E-01 65 0.0387 0.0256 1.3E-01 860 5.7E-01 Fish intake - DDR Eubacterium hallii 0.69% 0.92 Choline intake - FFQ 0.1123 0.1083 3.0E-01 65 0.0598 0.0255 1.9E-02 860 5.9E-01 Fish intake - DDR Eubacterium hallii 0.69% 0.92 Dairy intake - DDR 0.1072 0.1068 3.2E-01 65 0.0575 0.0250 2.1E-02 860 6.1E-01 Fish intake - DDR Eubacterium hallii 0.69% 0.92 Dairy intake - FFQ 0.1112 0.1076 3.1E-01 65 0.0561 0.0250 2.5E-02 860 5.9E-01 Fish intake - DDR Eubacterium hallii 0.69% 0.92 Egg intake - DDR 0.1104 0.1135 3.4E-01 65 0.0528 0.0250 3.5E-02 860 5.9E-01 Fish intake - DDR Eubacterium hallii 0.69% 0.92 Egg intake - FFQ 0.1095 0.1104 3.3E-01 65 0.0542 0.0250 3.0E-02 860 5.4E-01 Fish intake - DDR Eubacterium hallii 0.69% 0.92 Eubacterium biforme 0.0903 0.1136 4.3E-01 65 0.0528 0.0249 3.5E-02 860 6.4E-01 Fish intake - DDR Eubacterium hallii 0.69% 0.92 Fish intake - FFQ 0.0834 0.1105 4.5E-01 65 0.0318 0.0260 2.2E-01 860 6.2E-01 Fish intake - DDR Eubacterium hallii 0.69% 0.92 Plasma choline 0.1020 0.1076 3.5E-01 65 0.0569 0.0251 2.3E-02 860 6.1E-01 Fish intake - DDR Eubacterium hallii 0.69% 0.92 Plasma L-carnitine 0.0889 0.1126 4.3E-01 65 0.0526 0.0249 3.5E-02 860 6.7E-01 Fish intake - DDR Eubacterium hallii 0.69% 0.92 Red meat intake - DDR 0.0482 0.1115 6.7E-01 65 0.0551 0.0249 2.8E-02 860 3.5E-01 Fish intake - DDR Eubacterium hallii 0.69% 0.92 Red meat intake - FFQ 0.1019 0.1077 3.5E-01 65 0.0523 0.0251 3.8E-02 860 6.3E-01 Fish intake - DDR Eubacterium hallii 0.69% 0.92 Alistipes shahii 0.1098 0.1080 3.1E-01 65 0.0539 0.0250 3.1E-02 860 6.0E-01 Fish intake - DDR Eubacterium hallii 0.69% 0.92 Clostridiales bacterium 1 7 47FAA 0.1102 0.0963 2.6E-01 65 0.0525 0.0248 3.5E-02 860 5.8E-01 Fish intake - DDR Eubacterium hallii 0.69% 0.92 Clostridium citroniae 0.0852 0.1074 4.3E-01 65 0.0496 0.0248 4.6E-02 860 5.4E-01 Fish intake - DDR Eubacterium hallii 0.69% 0.92 Clostridium clostridioforme 0.1460 0.1070 1.8E-01 65 0.0519 0.0247 3.6E-02 860 9.1E-01 Fish intake - DDR Eubacterium hallii 0.69% 0.92 Clostridium nexile 0.1146 0.1072 2.9E-01 65 0.0551 0.0249 2.7E-02 860 7.2E-01 Fish intake - DDR Eubacterium hallii 0.69% 0.92 Eggerthella (unclassified) 0.0875 0.1083 4.2E-01 65 0.0527 0.0249 3.4E-02 860 6.3E-01 Fish intake - DDR Eubacterium hallii 0.69% 0.92 Erysipelotrichaceae bacterium 21 3 0.0929 0.1077 3.9E-01 65 0.0528 0.0250 3.5E-02 860 5.1E-01 Fish intake - DDR Eubacterium hallii 0.69% 0.92 Roseburia hominis 0.1129 0.1072 3.0E-01 65 0.0532 0.0247 3.2E-02 860 6.7E-01 Red meat intake - FFQ Roseburia hominis 0.58% 0.87 Fully adjusted -0.0410 0.2578 8.7E-01 103 0.0373 0.0678 5.8E-01 822 7.5E-01 Red meat intake - FFQ Roseburia hominis 0.58% 0.87 Choline intake - DDR -0.0130 0.2657 9.6E-01 103 0.0218 0.0677 7.5E-01 822 7.9E-01 Red meat intake - FFQ Roseburia hominis 0.58% 0.87 Choline intake - FFQ 0.0685 0.2598 7.9E-01 103 0.0050 0.0728 9.5E-01 822 7.2E-01 Red meat intake - FFQ Roseburia hominis 0.58% 0.87 Dairy intake - DDR -0.0313 0.2596 9.0E-01 103 0.0459 0.0679 5.0E-01 822 8.0E-01 Red meat intake - FFQ Roseburia hominis 0.58% 0.87 Dairy intake - FFQ -0.0047 0.2625 9.9E-01 103 0.0461 0.0677 5.0E-01 822 7.9E-01 Red meat intake - FFQ Roseburia hominis 0.58% 0.87 Egg intake - DDR -0.0351 0.2644 8.9E-01 103 0.0342 0.0681 6.2E-01 822 7.5E-01 Red meat intake - FFQ Roseburia hominis 0.58% 0.87 Egg intake - FFQ -0.0429 0.2645 8.7E-01 103 0.0200 0.0680 7.7E-01 822 7.3E-01 Red meat intake - FFQ Roseburia hominis 0.58% 0.87 Eubacterium biforme -0.0384 0.2602 8.8E-01 103 0.0383 0.0679 5.7E-01 822 7.4E-01 Red meat intake - FFQ Roseburia hominis 0.58% 0.87 Eubacterium hallii 0.0456 0.2555 8.6E-01 103 0.0351 0.0674 6.0E-01 822 6.0E-01 Red meat intake - FFQ Roseburia hominis 0.58% 0.87 Fish intake - DDR -0.0626 0.2545 8.1E-01 103 0.0380 0.0687 5.8E-01 822 7.9E-01 Red meat intake - FFQ Roseburia hominis 0.58% 0.87 Fish intake - FFQ -0.0333 0.2587 9.0E-01 103 0.0387 0.0679 5.7E-01 822 7.5E-01 Red meat intake - FFQ Roseburia hominis 0.58% 0.87 Plasma choline -0.0438 0.2606 8.7E-01 103 0.0365 0.0677 5.9E-01 822 6.7E-01 Red meat intake - FFQ Roseburia hominis 0.58% 0.87 Plasma L-carnitine 0.0729 0.2544 7.8E-01 103 0.0298 0.0675 6.6E-01 822 7.5E-01 Red meat intake - FFQ Roseburia hominis 0.58% 0.87 Red meat intake - DDR -0.0348 0.2882 9.0E-01 103 -0.0248 0.0742 7.4E-01 822 9.1E-01 Red meat intake - FFQ Roseburia hominis 0.58% 0.87 Alistipes shahii -0.0411 0.2589 8.7E-01 103 0.0346 0.0680 6.1E-01 822 7.5E-01 Red meat intake - FFQ Roseburia hominis 0.58% 0.87 Clostridiales bacterium 1 7 47FAA 0.0597 0.2610 8.2E-01 103 0.0236 0.0674 7.3E-01 822 5.6E-01 Red meat intake - FFQ Roseburia hominis 0.58% 0.87 Clostridium citroniae 0.0127 0.2640 9.6E-01 103 0.0549 0.0673 4.2E-01 822 6.9E-01 Red meat intake - FFQ Roseburia hominis 0.58% 0.87 Clostridium clostridioforme -0.0242 0.2623 9.3E-01 103 0.0268 0.0671 6.9E-01 822 4.7E-01 Red meat intake - FFQ Roseburia hominis 0.58% 0.87 Clostridium nexile -0.0417 0.2593 8.7E-01 103 0.0439 0.0675 5.2E-01 822 8.6E-01 Red meat intake - FFQ Roseburia hominis 0.58% 0.87 Eggerthella (unclassified) 0.1538 0.2637 5.6E-01 103 0.0383 0.0678 5.7E-01 822 5.1E-01 Red meat intake - FFQ Roseburia hominis 0.58% 0.87 Erysipelotrichaceae bacterium 21 3 -0.1457 0.2667 5.9E-01 103 0.0334 0.0677 6.2E-01 822 7.1E-01 Red meat intake - DDR Roseburia hominis 0.58% 0.87 Fully adjusted -0.0033 0.0587 9.6E-01 103 0.0423 0.0191 2.7E-02 822 6.7E-01 Red meat intake - DDR Roseburia hominis 0.58% 0.87 Choline intake - DDR 0.0246 0.0639 7.0E-01 103 0.0263 0.0202 1.9E-01 822 7.0E-01 Red meat intake - DDR Roseburia hominis 0.58% 0.87 Choline intake - FFQ -0.0017 0.0549 9.8E-01 103 0.0388 0.0196 4.8E-02 822 6.7E-01 Red meat intake - DDR Roseburia hominis 0.58% 0.87 Dairy intake - DDR -0.0031 0.0598 9.6E-01 103 0.0436 0.0190 2.2E-02 822 7.2E-01 Red meat intake - DDR Roseburia hominis 0.58% 0.87 Dairy intake - FFQ -0.0075 0.0607 9.0E-01 103 0.0459 0.0191 1.6E-02 822 7.6E-01 Red meat intake - DDR Roseburia hominis 0.58% 0.87 Egg intake - DDR -0.0069 0.0603 9.1E-01 103 0.0414 0.0191 3.1E-02 822 6.6E-01 Red meat intake - DDR Roseburia hominis 0.58% 0.87 Egg intake - FFQ 0.0042 0.0613 9.5E-01 103 0.0421 0.0191 2.8E-02 822 6.2E-01 Red meat intake - DDR Roseburia hominis 0.58% 0.87 Eubacterium biforme -0.0063 0.0593 9.2E-01 103 0.0432 0.0191 2.4E-02 822 6.6E-01 Red meat intake - DDR Roseburia hominis 0.58% 0.87 Eubacterium hallii 0.0052 0.0574 9.3E-01 103 0.0414 0.0190 2.9E-02 822 7.1E-01 Red meat intake - DDR Roseburia hominis 0.58% 0.87 Fish intake - DDR -0.0036 0.0588 9.5E-01 103 0.0427 0.0191 2.6E-02 822 6.6E-01 Red meat intake - DDR Roseburia hominis 0.58% 0.87 Fish intake - FFQ -0.0016 0.0589 9.8E-01 103 0.0458 0.0190 1.6E-02 822 6.5E-01 Red meat intake - DDR Roseburia hominis 0.58% 0.87 Plasma choline -0.0049 0.0597 9.3E-01 103 0.0418 0.0190 2.8E-02 822 7.3E-01 Red meat intake - DDR Roseburia hominis 0.58% 0.87 Plasma L-carnitine -0.0212 0.0575 7.1E-01 103 0.0350 0.0192 6.9E-02 822 8.0E-01 Red meat intake - DDR Roseburia hominis 0.58% 0.87 Red meat intake - FFQ 0.0169 0.0638 7.9E-01 103 0.0452 0.0206 2.9E-02 822 6.2E-01 Red meat intake - DDR Roseburia hominis 0.58% 0.87 Alistipes shahii -0.0056 0.0588 9.2E-01 103 0.0424 0.0191 2.6E-02 822 6.6E-01 Red meat intake - DDR Roseburia hominis 0.58% 0.87 Clostridiales bacterium 1 7 47FAA 0.0091 0.0581 8.8E-01 103 0.0388 0.0190 4.1E-02 822 7.5E-01 Red meat intake - DDR Roseburia hominis 0.58% 0.87 Clostridium citroniae -0.0161 0.0596 7.9E-01 103 0.0432 0.0189 2.2E-02 822 4.5E-01 Red meat intake - DDR Roseburia hominis 0.58% 0.87 Clostridium clostridioforme 0.0017 0.0594 9.8E-01 103 0.0424 0.0189 2.5E-02 822 9.4E-01 Red meat intake - DDR Roseburia hominis 0.58% 0.87 Clostridium nexile -0.0038 0.0591 9.5E-01 103 0.0434 0.0190 2.2E-02 822 5.9E-01 30

Supplementary Data 2a Absence (species)/ Non- Presence (species)/ Stratified by Dietary Exposure Additionally conditioned on producer (mixed score) TMAO-producer (mixed P-interaction Taxa Abundance Prevalence Effect Se P n Effect Se P n Red meat intake - DDR Roseburia hominis 0.58% 0.87 Eggerthella (unclassified) 0.0248 0.0583 6.7E-01 103 0.0439 0.0191 2.2E-02 822 8.1E-01 Red meat intake - DDR Roseburia hominis 0.58% 0.87 Erysipelotrichaceae bacterium 21 3 -0.0118 0.0584 8.4E-01 103 0.0430 0.0190 2.4E-02 822 6.6E-01 Choline intake - FFQ Roseburia hominis 0.58% 0.87 Fully adjusted -0.6098 0.2129 5.3E-03 103 0.1782 0.0553 1.3E-03 822 2.1E-03 Choline intake - FFQ Roseburia hominis 0.58% 0.87 Choline intake - DDR -0.6167 0.2203 6.4E-03 103 0.1445 0.0602 1.7E-02 822 2.3E-03 Choline intake - FFQ Roseburia hominis 0.58% 0.87 Dairy intake - DDR -0.6173 0.2138 5.0E-03 103 0.1671 0.0565 3.2E-03 822 3.0E-03 Choline intake - FFQ Roseburia hominis 0.58% 0.87 Dairy intake - FFQ -0.6168 0.2133 4.9E-03 103 0.1583 0.0587 7.1E-03 822 2.4E-03 Choline intake - FFQ Roseburia hominis 0.58% 0.87 Egg intake - DDR -0.6602 0.2246 4.3E-03 103 0.1896 0.0577 1.1E-03 822 2.1E-03 Choline intake - FFQ Roseburia hominis 0.58% 0.87 Egg intake - FFQ -0.7255 0.2326 2.5E-03 103 0.1448 0.0652 2.7E-02 822 3.0E-03 Choline intake - FFQ Roseburia hominis 0.58% 0.87 Eubacterium biforme -0.6097 0.2144 5.6E-03 103 0.1778 0.0554 1.4E-03 822 2.1E-03 Choline intake - FFQ Roseburia hominis 0.58% 0.87 Eubacterium hallii -0.6919 0.2060 1.2E-03 103 0.1716 0.0550 1.9E-03 822 1.6E-03 Choline intake - FFQ Roseburia hominis 0.58% 0.87 Fish intake - DDR -0.6480 0.1962 1.4E-03 103 0.1999 0.0551 3.1E-04 822 4.6E-03 Choline intake - FFQ Roseburia hominis 0.58% 0.87 Fish intake - FFQ -0.6449 0.2070 2.5E-03 103 0.1783 0.0554 1.4E-03 822 2.0E-03 Choline intake - FFQ Roseburia hominis 0.58% 0.87 Plasma choline -0.6132 0.2145 5.4E-03 103 0.1734 0.0553 1.8E-03 822 2.4E-03 Choline intake - FFQ Roseburia hominis 0.58% 0.87 Plasma L-carnitine -0.5098 0.2145 2.0E-02 103 0.1590 0.0556 4.4E-03 822 1.7E-03 Choline intake - FFQ Roseburia hominis 0.58% 0.87 Red meat intake - DDR -0.5897 0.2150 7.5E-03 103 0.1576 0.0565 5.4E-03 822 3.6E-03 Choline intake - FFQ Roseburia hominis 0.58% 0.87 Red meat intake - FFQ -0.6192 0.2171 5.5E-03 103 0.1747 0.0579 2.6E-03 822 2.6E-03 Choline intake - FFQ Roseburia hominis 0.58% 0.87 Alistipes shahii -0.6061 0.2144 5.9E-03 103 0.1811 0.0554 1.1E-03 822 1.8E-03 Choline intake - FFQ Roseburia hominis 0.58% 0.87 Clostridiales bacterium 1 7 47FAA -0.5749 0.2124 8.2E-03 103 0.1803 0.0550 1.1E-03 822 3.1E-03 Choline intake - FFQ Roseburia hominis 0.58% 0.87 Clostridium citroniae -0.6207 0.2127 4.5E-03 103 0.1751 0.0548 1.5E-03 822 1.6E-03 Choline intake - FFQ Roseburia hominis 0.58% 0.87 Clostridium clostridioforme -0.6152 0.2187 6.1E-03 103 0.1736 0.0547 1.6E-03 822 5.2E-03 Choline intake - FFQ Roseburia hominis 0.58% 0.87 Clostridium nexile -0.6112 0.2143 5.5E-03 103 0.1715 0.0552 2.0E-03 822 3.6E-04 Choline intake - FFQ Roseburia hominis 0.58% 0.87 Eggerthella (unclassified) -0.5092 0.2107 1.8E-02 103 0.1766 0.0554 1.5E-03 822 2.4E-03 Choline intake - FFQ Roseburia hominis 0.58% 0.87 Erysipelotrichaceae bacterium 21 3 -0.5799 0.2154 8.6E-03 103 0.1719 0.0554 2.0E-03 822 1.8E-03 Choline intake - DDR Roseburia hominis 0.58% 0.87 Fully adjusted -0.1261 0.1463 3.9E-01 103 0.1216 0.0424 4.3E-03 822 5.0E-02 Choline intake - DDR Roseburia hominis 0.58% 0.87 Choline intake - FFQ -0.0235 0.1379 8.7E-01 103 0.0800 0.0458 8.1E-02 822 4.9E-02 Choline intake - DDR Roseburia hominis 0.58% 0.87 Dairy intake - DDR -0.1252 0.1470 4.0E-01 103 0.1156 0.0425 6.7E-03 822 5.9E-02 Choline intake - DDR Roseburia hominis 0.58% 0.87 Dairy intake - FFQ -0.1228 0.1471 4.1E-01 103 0.1107 0.0432 1.0E-02 822 6.1E-02 Choline intake - DDR Roseburia hominis 0.58% 0.87 Egg intake - DDR -0.3265 0.2164 1.3E-01 103 0.1852 0.0558 9.5E-04 822 4.9E-02 Choline intake - DDR Roseburia hominis 0.58% 0.87 Egg intake - FFQ -0.1110 0.1597 4.9E-01 103 0.1064 0.0445 1.7E-02 822 5.2E-02 Choline intake - DDR Roseburia hominis 0.58% 0.87 Eubacterium biforme -0.1307 0.1474 3.8E-01 103 0.1211 0.0425 4.5E-03 822 5.1E-02 Choline intake - DDR Roseburia hominis 0.58% 0.87 Eubacterium hallii -0.1448 0.1427 3.1E-01 103 0.1178 0.0422 5.4E-03 822 4.3E-02 Choline intake - DDR Roseburia hominis 0.58% 0.87 Fish intake - DDR -0.1535 0.1463 3.0E-01 103 0.1308 0.0428 2.3E-03 822 4.3E-02 Choline intake - DDR Roseburia hominis 0.58% 0.87 Fish intake - FFQ -0.1248 0.1464 4.0E-01 103 0.1228 0.0423 3.8E-03 822 3.2E-02 Choline intake - DDR Roseburia hominis 0.58% 0.87 Plasma choline -0.1264 0.1471 3.9E-01 103 0.1191 0.0424 5.1E-03 822 5.4E-02 Choline intake - DDR Roseburia hominis 0.58% 0.87 Plasma L-carnitine -0.1007 0.1424 4.8E-01 103 0.1121 0.0424 8.4E-03 822 5.1E-02 Choline intake - DDR Roseburia hominis 0.58% 0.87 Red meat intake - DDR -0.1758 0.1596 2.7E-01 103 0.1048 0.0452 2.1E-02 822 2.1E-02 Choline intake - DDR Roseburia hominis 0.58% 0.87 Red meat intake - FFQ -0.1146 0.1476 4.4E-01 103 0.1221 0.0430 4.6E-03 822 5.4E-02 Choline intake - DDR Roseburia hominis 0.58% 0.87 Alistipes shahii -0.1286 0.1462 3.8E-01 103 0.1242 0.0425 3.6E-03 822 4.7E-02 Choline intake - DDR Roseburia hominis 0.58% 0.87 Clostridiales bacterium 1 7 47FAA -0.1148 0.1449 4.3E-01 103 0.1179 0.0422 5.3E-03 822 4.3E-02 Choline intake - DDR Roseburia hominis 0.58% 0.87 Clostridium citroniae -0.1427 0.1469 3.3E-01 103 0.1169 0.0421 5.6E-03 822 3.9E-02 Choline intake - DDR Roseburia hominis 0.58% 0.87 Clostridium clostridioforme -0.1180 0.1477 4.3E-01 103 0.1187 0.0420 4.9E-03 822 6.0E-02 Choline intake - DDR Roseburia hominis 0.58% 0.87 Clostridium nexile -0.1283 0.1472 3.9E-01 103 0.1243 0.0423 3.4E-03 822 2.5E-02 Choline intake - DDR Roseburia hominis 0.58% 0.87 Eggerthella (unclassified) -0.0831 0.1440 5.7E-01 103 0.1216 0.0424 4.3E-03 822 5.0E-02 Choline intake - DDR Roseburia hominis 0.58% 0.87 Erysipelotrichaceae bacterium 21 3 -0.1127 0.1449 4.4E-01 103 0.1209 0.0424 4.4E-03 822 4.8E-02 Plasma choline Roseburia hominis 0.58% 0.87 Fully adjusted -0.0113 0.1312 9.3E-01 103 0.0614 0.0343 7.4E-02 822 5.1E-01 Plasma choline Roseburia hominis 0.58% 0.87 Choline intake - DDR -0.0157 0.1320 9.1E-01 103 0.0559 0.0342 1.0E-01 822 5.6E-01 Plasma choline Roseburia hominis 0.58% 0.87 Choline intake - FFQ -0.0327 0.1285 8.0E-01 103 0.0589 0.0345 8.8E-02 822 5.8E-01 Plasma choline Roseburia hominis 0.58% 0.87 Dairy intake - DDR -0.0183 0.1324 8.9E-01 103 0.0575 0.0344 9.5E-02 822 5.7E-01 Plasma choline Roseburia hominis 0.58% 0.87 Dairy intake - FFQ -0.0024 0.1319 9.9E-01 103 0.0602 0.0342 7.9E-02 822 5.3E-01 Plasma choline Roseburia hominis 0.58% 0.87 Egg intake - DDR -0.0117 0.1319 9.3E-01 103 0.0609 0.0344 7.7E-02 822 5.1E-01 Plasma choline Roseburia hominis 0.58% 0.87 Egg intake - FFQ -0.0114 0.1322 9.3E-01 103 0.0579 0.0342 9.1E-02 822 4.9E-01 Plasma choline Roseburia hominis 0.58% 0.87 Eubacterium biforme -0.0125 0.1322 9.3E-01 103 0.0607 0.0344 7.7E-02 822 5.1E-01 Plasma choline Roseburia hominis 0.58% 0.87 Eubacterium hallii -0.0147 0.1284 9.1E-01 103 0.0589 0.0341 8.4E-02 822 5.5E-01 Plasma choline Roseburia hominis 0.58% 0.87 Fish intake - DDR 0.0347 0.1306 7.9E-01 103 0.0566 0.0341 9.7E-02 822 5.4E-01 Plasma choline Roseburia hominis 0.58% 0.87 Fish intake - FFQ -0.0036 0.1330 9.8E-01 103 0.0593 0.0343 8.4E-02 822 5.6E-01 Plasma choline Roseburia hominis 0.58% 0.87 Plasma L-carnitine 0.0215 0.1281 8.7E-01 103 0.0392 0.0352 2.7E-01 822 5.6E-01 Plasma choline Roseburia hominis 0.58% 0.87 Red meat intake - DDR -0.0143 0.1325 9.1E-01 103 0.0567 0.0343 9.9E-02 822 6.0E-01 Plasma choline Roseburia hominis 0.58% 0.87 Red meat intake - FFQ -0.0136 0.1326 9.2E-01 103 0.0650 0.0344 5.9E-02 822 5.0E-01 Plasma choline Roseburia hominis 0.58% 0.87 Alistipes shahii -0.0318 0.1375 8.2E-01 103 0.0623 0.0343 7.0E-02 822 5.3E-01 Plasma choline Roseburia hominis 0.58% 0.87 Clostridiales bacterium 1 7 47FAA -0.0309 0.1301 8.1E-01 103 0.0641 0.0340 6.0E-02 822 4.0E-01 Plasma choline Roseburia hominis 0.58% 0.87 Clostridium citroniae -0.0078 0.1313 9.5E-01 103 0.0548 0.0340 1.1E-01 822 5.6E-01 Plasma choline Roseburia hominis 0.58% 0.87 Clostridium clostridioforme -0.0018 0.1338 9.9E-01 103 0.0681 0.0340 4.5E-02 822 7.3E-01 Plasma choline Roseburia hominis 0.58% 0.87 Clostridium nexile -0.0135 0.1331 9.2E-01 103 0.0726 0.0343 3.5E-02 822 3.8E-01 Plasma choline Roseburia hominis 0.58% 0.87 Eggerthella (unclassified) 0.0051 0.1281 9.7E-01 103 0.0601 0.0343 8.0E-02 822 5.6E-01 Plasma choline Roseburia hominis 0.58% 0.87 Erysipelotrichaceae bacterium 21 3 -0.0278 0.1312 8.3E-01 103 0.0664 0.0343 5.3E-02 822 5.0E-01 Plasma L-carnitine Roseburia hominis 0.58% 0.87 Fully adjusted -0.3591 0.1431 1.4E-02 103 0.0950 0.0322 3.3E-03 822 1.0E-02 Plasma L-carnitine Roseburia hominis 0.58% 0.87 Choline intake - DDR -0.3558 0.1441 1.6E-02 103 0.0865 0.0323 7.5E-03 822 1.4E-02 Plasma L-carnitine Roseburia hominis 0.58% 0.87 Choline intake - FFQ -0.3062 0.1489 4.3E-02 103 0.0860 0.0327 8.7E-03 822 8.5E-03 Plasma L-carnitine Roseburia hominis 0.58% 0.87 Dairy intake - DDR -0.3549 0.1445 1.6E-02 103 0.0891 0.0325 6.3E-03 822 1.1E-02 Plasma L-carnitine Roseburia hominis 0.58% 0.87 Dairy intake - FFQ -0.3576 0.1434 1.5E-02 103 0.0898 0.0322 5.5E-03 822 1.1E-02 Plasma L-carnitine Roseburia hominis 0.58% 0.87 Egg intake - DDR -0.3733 0.1476 1.3E-02 103 0.0946 0.0322 3.4E-03 822 8.7E-03 Plasma L-carnitine Roseburia hominis 0.58% 0.87 Egg intake - FFQ -0.3738 0.1466 1.3E-02 103 0.0898 0.0322 5.4E-03 822 7.7E-03 Plasma L-carnitine Roseburia hominis 0.58% 0.87 Eubacterium biforme -0.3588 0.1440 1.5E-02 103 0.0959 0.0322 3.0E-03 822 1.0E-02 Plasma L-carnitine Roseburia hominis 0.58% 0.87 Eubacterium hallii -0.2848 0.1510 6.3E-02 103 0.0926 0.0320 3.9E-03 822 2.7E-02 Plasma L-carnitine Roseburia hominis 0.58% 0.87 Fish intake - DDR -0.3480 0.1407 1.5E-02 103 0.0909 0.0320 4.6E-03 822 2.4E-02 Plasma L-carnitine Roseburia hominis 0.58% 0.87 Fish intake - FFQ -0.3705 0.1426 1.1E-02 103 0.0940 0.0322 3.6E-03 822 9.4E-03 Plasma L-carnitine Roseburia hominis 0.58% 0.87 Plasma choline -0.3616 0.1447 1.4E-02 103 0.0860 0.0332 9.7E-03 822 1.2E-02 Plasma L-carnitine Roseburia hominis 0.58% 0.87 Red meat intake - DDR -0.3592 0.1446 1.5E-02 103 0.0838 0.0326 1.0E-02 822 2.3E-02 Plasma L-carnitine Roseburia hominis 0.58% 0.87 Red meat intake - FFQ -0.3665 0.1462 1.4E-02 103 0.0944 0.0322 3.5E-03 822 1.1E-02 Plasma L-carnitine Roseburia hominis 0.58% 0.87 Alistipes shahii -0.3613 0.1437 1.4E-02 103 0.0945 0.0322 3.5E-03 822 1.1E-02 31

Supplementary Data 2a Absence (species)/ Non- Presence (species)/ Stratified by Dietary Exposure Additionally conditioned on producer (mixed score) TMAO-producer (mixed P-interaction Taxa Abundance Prevalence Effect Se P n Effect Se P n Plasma L-carnitine Roseburia hominis 0.58% 0.87 Clostridiales bacterium 1 7 47FAA -0.3275 0.1439 2.5E-02 103 0.0921 0.0320 4.1E-03 822 1.9E-02 Plasma L-carnitine Roseburia hominis 0.58% 0.87 Clostridium citroniae -0.3452 0.1491 2.3E-02 103 0.0913 0.0319 4.4E-03 822 2.6E-02 Plasma L-carnitine Roseburia hominis 0.58% 0.87 Clostridium clostridioforme -0.3565 0.1449 1.6E-02 103 0.0898 0.0319 5.0E-03 822 1.3E-02 Plasma L-carnitine Roseburia hominis 0.58% 0.87 Clostridium nexile -0.3636 0.1445 1.4E-02 103 0.1003 0.0321 1.8E-03 822 4.1E-02 Plasma L-carnitine Roseburia hominis 0.58% 0.87 Eggerthella (unclassified) -0.2602 0.1591 1.1E-01 103 0.0958 0.0322 3.0E-03 822 2.1E-02 Plasma L-carnitine Roseburia hominis 0.58% 0.87 Erysipelotrichaceae bacterium 21 3 -0.3784 0.1424 9.4E-03 103 0.0981 0.0322 2.4E-03 822 1.1E-02 Dairy intake - FFQ Roseburia hominis 0.58% 0.87 Fully adjusted 0.0703 0.0879 4.3E-01 103 0.0598 0.0274 2.9E-02 822 7.8E-01 Dairy intake - FFQ Roseburia hominis 0.58% 0.87 Choline intake - DDR 0.0754 0.0887 4.0E-01 103 0.0459 0.0279 1.0E-01 822 7.2E-01 Dairy intake - FFQ Roseburia hominis 0.58% 0.87 Choline intake - FFQ 0.0785 0.0875 3.7E-01 103 0.0302 0.0297 3.1E-01 822 5.5E-01 Dairy intake - FFQ Roseburia hominis 0.58% 0.87 Dairy intake - DDR 0.1368 0.1049 2.0E-01 103 0.0499 0.0330 1.3E-01 822 7.8E-01 Dairy intake - FFQ Roseburia hominis 0.58% 0.87 Egg intake - DDR 0.0704 0.0884 4.3E-01 103 0.0598 0.0274 2.9E-02 822 7.7E-01 Dairy intake - FFQ Roseburia hominis 0.58% 0.87 Egg intake - FFQ 0.0704 0.0885 4.3E-01 103 0.0549 0.0274 4.5E-02 822 7.1E-01 Dairy intake - FFQ Roseburia hominis 0.58% 0.87 Eubacterium biforme 0.0699 0.0892 4.4E-01 103 0.0593 0.0274 3.1E-02 822 7.8E-01 Dairy intake - FFQ Roseburia hominis 0.58% 0.87 Eubacterium hallii 0.0733 0.0861 4.0E-01 103 0.0601 0.0272 2.7E-02 822 7.6E-01 Dairy intake - FFQ Roseburia hominis 0.58% 0.87 Fish intake - DDR 0.0760 0.0861 3.8E-01 103 0.0526 0.0275 5.6E-02 822 7.6E-01 Dairy intake - FFQ Roseburia hominis 0.58% 0.87 Fish intake - FFQ 0.0794 0.0891 3.8E-01 103 0.0617 0.0274 2.5E-02 822 7.7E-01 Dairy intake - FFQ Roseburia hominis 0.58% 0.87 Plasma choline 0.0702 0.0888 4.3E-01 103 0.0591 0.0273 3.1E-02 822 7.5E-01 Dairy intake - FFQ Roseburia hominis 0.58% 0.87 Plasma L-carnitine 0.0675 0.0854 4.3E-01 103 0.0536 0.0273 5.0E-02 822 7.1E-01 Dairy intake - FFQ Roseburia hominis 0.58% 0.87 Red meat intake - DDR 0.0736 0.0903 4.2E-01 103 0.0581 0.0273 3.3E-02 822 6.4E-01 Dairy intake - FFQ Roseburia hominis 0.58% 0.87 Red meat intake - FFQ 0.0700 0.0899 4.4E-01 103 0.0662 0.0276 1.7E-02 822 7.9E-01 Dairy intake - FFQ Roseburia hominis 0.58% 0.87 Alistipes shahii 0.0649 0.0899 4.7E-01 103 0.0600 0.0274 2.9E-02 822 7.8E-01 Dairy intake - FFQ Roseburia hominis 0.58% 0.87 Clostridiales bacterium 1 7 47FAA 0.0786 0.0869 3.7E-01 103 0.0611 0.0271 2.5E-02 822 7.5E-01 Dairy intake - FFQ Roseburia hominis 0.58% 0.87 Clostridium citroniae 0.1047 0.0917 2.6E-01 103 0.0599 0.0271 2.7E-02 822 6.7E-01 Dairy intake - FFQ Roseburia hominis 0.58% 0.87 Clostridium clostridioforme 0.0649 0.0913 4.8E-01 103 0.0593 0.0271 2.9E-02 822 9.3E-01 Dairy intake - FFQ Roseburia hominis 0.58% 0.87 Clostridium nexile 0.0701 0.0885 4.3E-01 103 0.0579 0.0272 3.4E-02 822 9.9E-01 Dairy intake - FFQ Roseburia hominis 0.58% 0.87 Eggerthella (unclassified) 0.0294 0.0880 7.4E-01 103 0.0592 0.0274 3.1E-02 822 8.4E-01 Dairy intake - FFQ Roseburia hominis 0.58% 0.87 Erysipelotrichaceae bacterium 21 3 0.1193 0.0918 2.0E-01 103 0.0583 0.0273 3.3E-02 822 8.4E-01 Dairy intake - DDR Roseburia hominis 0.58% 0.87 Fully adjusted -0.0368 0.0848 6.7E-01 103 0.0539 0.0272 4.8E-02 822 3.0E-01 Dairy intake - DDR Roseburia hominis 0.58% 0.87 Choline intake - DDR -0.0358 0.0849 6.7E-01 103 0.0479 0.0271 7.8E-02 822 3.8E-01 Dairy intake - DDR Roseburia hominis 0.58% 0.87 Choline intake - FFQ -0.0505 0.0779 5.2E-01 103 0.0490 0.0276 7.7E-02 822 3.7E-01 Dairy intake - DDR Roseburia hominis 0.58% 0.87 Dairy intake - FFQ -0.0210 0.0982 8.3E-01 103 0.0373 0.0314 2.3E-01 822 3.2E-01 Dairy intake - DDR Roseburia hominis 0.58% 0.87 Egg intake - DDR -0.0355 0.0857 6.8E-01 103 0.0558 0.0273 4.1E-02 822 3.2E-01 Dairy intake - DDR Roseburia hominis 0.58% 0.87 Egg intake - FFQ -0.0367 0.0851 6.7E-01 103 0.0555 0.0271 4.1E-02 822 3.3E-01 Dairy intake - DDR Roseburia hominis 0.58% 0.87 Eubacterium biforme -0.0350 0.0854 6.8E-01 103 0.0535 0.0272 5.0E-02 822 3.1E-01 Dairy intake - DDR Roseburia hominis 0.58% 0.87 Eubacterium hallii -0.0139 0.0835 8.7E-01 103 0.0529 0.0270 5.1E-02 822 3.8E-01 Dairy intake - DDR Roseburia hominis 0.58% 0.87 Fish intake - DDR -0.0277 0.0847 7.4E-01 103 0.0505 0.0273 6.5E-02 822 3.2E-01 Dairy intake - DDR Roseburia hominis 0.58% 0.87 Fish intake - FFQ -0.0409 0.0849 6.3E-01 103 0.0482 0.0272 7.7E-02 822 3.9E-01 Dairy intake - DDR Roseburia hominis 0.58% 0.87 Plasma choline -0.0384 0.0856 6.5E-01 103 0.0528 0.0271 5.2E-02 822 3.4E-01 Dairy intake - DDR Roseburia hominis 0.58% 0.87 Plasma L-carnitine -0.0188 0.0826 8.2E-01 103 0.0451 0.0273 9.8E-02 822 3.4E-01 Dairy intake - DDR Roseburia hominis 0.58% 0.87 Red meat intake - DDR 0.0014 0.0904 9.9E-01 103 0.0550 0.0271 4.3E-02 822 4.7E-01 Dairy intake - DDR Roseburia hominis 0.58% 0.87 Red meat intake - FFQ -0.0358 0.0850 6.7E-01 103 0.0585 0.0273 3.3E-02 822 2.9E-01 Dairy intake - DDR Roseburia hominis 0.58% 0.87 Alistipes shahii -0.0510 0.0856 5.5E-01 103 0.0555 0.0272 4.2E-02 822 3.0E-01 Dairy intake - DDR Roseburia hominis 0.58% 0.87 Clostridiales bacterium 1 7 47FAA -0.0313 0.0839 7.1E-01 103 0.0591 0.0270 2.9E-02 822 2.8E-01 Dairy intake - DDR Roseburia hominis 0.58% 0.87 Clostridium citroniae -0.0168 0.0876 8.5E-01 103 0.0596 0.0270 2.7E-02 822 3.6E-01 Dairy intake - DDR Roseburia hominis 0.58% 0.87 Clostridium clostridioforme -0.0637 0.0911 4.9E-01 103 0.0526 0.0269 5.1E-02 822 8.4E-02 Dairy intake - DDR Roseburia hominis 0.58% 0.87 Clostridium nexile -0.0368 0.0853 6.7E-01 103 0.0528 0.0271 5.2E-02 822 4.6E-01 Dairy intake - DDR Roseburia hominis 0.58% 0.87 Eggerthella (unclassified) -0.0430 0.0826 6.0E-01 103 0.0541 0.0272 4.7E-02 822 3.1E-01 Dairy intake - DDR Roseburia hominis 0.58% 0.87 Erysipelotrichaceae bacterium 21 3 -0.0120 0.0852 8.9E-01 103 0.0510 0.0272 6.1E-02 822 2.9E-01 Egg intake - FFQ Roseburia hominis 0.58% 0.87 Fully adjusted 0.0011 0.3183 1.0E+00 103 0.1942 0.0838 2.1E-02 822 9.5E-01 Egg intake - FFQ Roseburia hominis 0.58% 0.87 Choline intake - DDR 0.0669 0.3427 8.5E-01 103 0.1435 0.0865 9.7E-02 822 9.7E-01 Egg intake - FFQ Roseburia hominis 0.58% 0.87 Choline intake - FFQ 0.4523 0.3713 2.3E-01 103 0.0971 0.1003 3.3E-01 822 9.3E-01 Egg intake - FFQ Roseburia hominis 0.58% 0.87 Dairy intake - DDR 0.0019 0.3197 1.0E+00 103 0.1897 0.0837 2.4E-02 822 9.3E-01 Egg intake - FFQ Roseburia hominis 0.58% 0.87 Dairy intake - FFQ -0.0068 0.3192 9.8E-01 103 0.1802 0.0839 3.2E-02 822 9.9E-01 Egg intake - FFQ Roseburia hominis 0.58% 0.87 Egg intake - DDR 0.0414 0.3921 9.2E-01 103 0.2166 0.0932 2.0E-02 822 9.5E-01 Egg intake - FFQ Roseburia hominis 0.58% 0.87 Eubacterium biforme 0.0060 0.3221 9.9E-01 103 0.1928 0.0839 2.2E-02 822 9.5E-01 Egg intake - FFQ Roseburia hominis 0.58% 0.87 Eubacterium hallii -0.1067 0.3153 7.4E-01 103 0.2048 0.0833 1.4E-02 822 7.8E-01 Egg intake - FFQ Roseburia hominis 0.58% 0.87 Fish intake - DDR -0.0081 0.3136 9.8E-01 103 0.1638 0.0841 5.2E-02 822 8.7E-01 Egg intake - FFQ Roseburia hominis 0.58% 0.87 Fish intake - FFQ 0.0175 0.3202 9.6E-01 103 0.1959 0.0839 2.0E-02 822 9.7E-01 Egg intake - FFQ Roseburia hominis 0.58% 0.87 Plasma choline 0.0028 0.3208 9.9E-01 103 0.1878 0.0837 2.5E-02 822 9.5E-01 Egg intake - FFQ Roseburia hominis 0.58% 0.87 Plasma L-carnitine 0.1601 0.3150 6.1E-01 103 0.1766 0.0836 3.5E-02 822 9.3E-01 Egg intake - FFQ Roseburia hominis 0.58% 0.87 Red meat intake - DDR 0.0490 0.3309 8.8E-01 103 0.1774 0.0839 3.5E-02 822 9.4E-01 Egg intake - FFQ Roseburia hominis 0.58% 0.87 Red meat intake - FFQ 0.0116 0.3266 9.7E-01 103 0.2030 0.0846 1.7E-02 822 9.7E-01 Egg intake - FFQ Roseburia hominis 0.58% 0.87 Alistipes shahii 0.0003 0.3198 1.0E+00 103 0.1926 0.0839 2.2E-02 822 9.5E-01 Egg intake - FFQ Roseburia hominis 0.58% 0.87 Clostridiales bacterium 1 7 47FAA 0.1054 0.3197 7.4E-01 103 0.1860 0.0832 2.6E-02 822 7.4E-01 Egg intake - FFQ Roseburia hominis 0.58% 0.87 Clostridium citroniae -0.0053 0.3185 9.9E-01 103 0.1719 0.0832 3.9E-02 822 9.1E-01 Egg intake - FFQ Roseburia hominis 0.58% 0.87 Clostridium clostridioforme -0.0043 0.3201 9.9E-01 103 0.2019 0.0829 1.5E-02 822 9.4E-01 Egg intake - FFQ Roseburia hominis 0.58% 0.87 Clostridium nexile -0.0009 0.3207 1.0E+00 103 0.1869 0.0835 2.5E-02 822 8.5E-01 Egg intake - FFQ Roseburia hominis 0.58% 0.87 Eggerthella (unclassified) 0.0028 0.3105 9.9E-01 103 0.1916 0.0838 2.3E-02 822 9.9E-01 Egg intake - FFQ Roseburia hominis 0.58% 0.87 Erysipelotrichaceae bacterium 21 3 -0.0360 0.3182 9.1E-01 103 0.1812 0.0840 3.1E-02 822 9.2E-01 Egg intake - DDR Roseburia hominis 0.58% 0.87 Fully adjusted 0.0449 0.2205 8.4E-01 103 0.0384 0.0652 5.6E-01 822 6.6E-01 Egg intake - DDR Roseburia hominis 0.58% 0.87 Choline intake - DDR 0.4072 0.3249 2.1E-01 103 -0.1412 0.0845 9.5E-02 822 7.1E-01 Egg intake - DDR Roseburia hominis 0.58% 0.87 Choline intake - FFQ 0.1269 0.1985 5.2E-01 103 -0.0430 0.0695 5.4E-01 822 5.6E-01 Egg intake - DDR Roseburia hominis 0.58% 0.87 Dairy intake - DDR 0.0362 0.2226 8.7E-01 103 0.0500 0.0654 4.4E-01 822 6.4E-01 Egg intake - DDR Roseburia hominis 0.58% 0.87 Dairy intake - FFQ 0.0439 0.2215 8.4E-01 103 0.0311 0.0652 6.3E-01 822 6.8E-01 Egg intake - DDR Roseburia hominis 0.58% 0.87 Egg intake - FFQ 0.1648 0.2662 5.4E-01 103 -0.0314 0.0729 6.7E-01 822 6.7E-01 Egg intake - DDR Roseburia hominis 0.58% 0.87 Eubacterium biforme 0.0371 0.2229 8.7E-01 103 0.0373 0.0653 5.7E-01 822 6.5E-01 Egg intake - DDR Roseburia hominis 0.58% 0.87 Eubacterium hallii -0.0100 0.2166 9.6E-01 103 0.0481 0.0649 4.6E-01 822 8.5E-01 Egg intake - DDR Roseburia hominis 0.58% 0.87 Fish intake - DDR 0.0469 0.2194 8.3E-01 103 0.0441 0.0655 5.0E-01 822 6.7E-01 Egg intake - DDR Roseburia hominis 0.58% 0.87 Fish intake - FFQ 0.0030 0.2253 9.9E-01 103 0.0250 0.0651 7.0E-01 822 6.5E-01 Egg intake - DDR Roseburia hominis 0.58% 0.87 Plasma choline 0.0444 0.2218 8.4E-01 103 0.0339 0.0652 6.0E-01 822 6.4E-01 32

Supplementary Data 2b Supplementary Data 2b. Associations of intakes of choline and red meat, or other TMAO precursors with TMAO levels, stratified by TMAO-producer phenotype, additionally adjusted for other TMAO precursors. Full model was adjusted for age, BMI, physical activity, energy intake, smoking, cumulative dietary quality, antibiotics use, probiotics use, the Bristol Stool Chart, and/or fish intake (for non-fish dietary variables). Absence (species)/ Non- Presence (species)/ Dietary Exposure Additionally conditioned on producer (mixed score) TMAO-producer (mixed P-interaction Effect Se P n Effect Se P n Red meat intake - FFQ Fully adjusted -0.1770 0.1025 8.5E-02 472 0.1928 0.0846 2.3E-02 453 2.7E-03 Red meat intake - FFQ Choline intake - DDR -0.1875 0.1040 7.2E-02 472 0.1828 0.0842 3.0E-02 453 1.5E-03 Red meat intake - FFQ Choline intake - FFQ -0.1715 0.1090 1.2E-01 472 0.1957 0.0931 3.6E-02 453 1.6E-03 Red meat intake - FFQ Dairy intake - DDR -0.1729 0.1023 9.2E-02 472 0.1882 0.0851 2.8E-02 453 2.2E-03 Red meat intake - FFQ Dairy intake - FFQ -0.1518 0.1024 1.4E-01 472 0.1947 0.0847 2.2E-02 453 2.8E-03 Red meat intake - FFQ Egg intake - DDR -0.1866 0.1036 7.2E-02 472 0.1897 0.0849 2.6E-02 453 2.3E-03 Red meat intake - FFQ Egg intake - FFQ -0.1728 0.1023 9.2E-02 472 0.1856 0.0877 3.5E-02 453 5.5E-03 Red meat intake - FFQ Fish intake - DDR -0.1663 0.1028 1.1E-01 472 0.1865 0.0858 3.0E-02 453 2.9E-03 Red meat intake - FFQ Fish intake - FFQ -0.1803 0.1025 7.9E-02 472 0.1982 0.0846 2.0E-02 453 2.2E-03 Red meat intake - FFQ Plasma choline -0.1781 0.1027 8.3E-02 472 0.1912 0.0840 2.3E-02 453 3.3E-03 Red meat intake - FFQ Plasma L-carnitine -0.1799 0.1026 8.0E-02 472 0.1848 0.0844 2.9E-02 453 2.8E-03 Red meat intake - FFQ Red meat intake - DDR -0.2135 0.1128 5.9E-02 472 0.1111 0.0927 2.3E-01 453 2.0E-03 Red meat intake - DDR Fully adjusted 0.0161 0.0267 5.5E-01 472 0.0620 0.0253 1.5E-02 453 1.0E-01 Red meat intake - DDR Choline intake - DDR 0.0089 0.0283 7.5E-01 472 0.0465 0.0274 9.0E-02 453 1.3E-01 Red meat intake - DDR Choline intake - FFQ 0.0210 0.0279 4.5E-01 472 0.0547 0.0260 3.6E-02 453 1.5E-01 Red meat intake - DDR Dairy intake - DDR 0.0160 0.0266 5.5E-01 472 0.0605 0.0255 1.8E-02 453 7.9E-02 Red meat intake - DDR Dairy intake - FFQ 0.0232 0.0268 3.9E-01 472 0.0621 0.0253 1.5E-02 453 1.1E-01 Red meat intake - DDR Egg intake - DDR 0.0153 0.0269 5.7E-01 472 0.0617 0.0257 1.7E-02 453 1.1E-01 Red meat intake - DDR Egg intake - FFQ 0.0182 0.0269 5.0E-01 472 0.0613 0.0256 1.7E-02 453 1.4E-01 Red meat intake - DDR Fish intake - DDR 0.0173 0.0268 5.2E-01 472 0.0636 0.0253 1.2E-02 453 9.1E-02 Red meat intake - DDR Fish intake - FFQ 0.0152 0.0271 5.7E-01 472 0.0736 0.0253 3.8E-03 453 5.4E-02 Red meat intake - DDR Plasma choline 0.0161 0.0268 5.5E-01 472 0.0590 0.0252 2.0E-02 453 1.1E-01 Red meat intake - DDR Plasma L-carnitine 0.0151 0.0268 5.7E-01 472 0.0550 0.0260 3.5E-02 453 1.5E-01 Red meat intake - DDR Red meat intake - FFQ 0.0395 0.0287 1.7E-01 472 0.0493 0.0276 7.5E-02 453 1.1E-01 Choline intake - FFQ Fully adjusted 0.0179 0.0769 8.2E-01 472 0.1870 0.0755 1.4E-02 453 3.0E-02 Choline intake - FFQ Choline intake - DDR 0.0146 0.0841 8.6E-01 472 0.1390 0.0805 8.5E-02 453 2.3E-02 Choline intake - FFQ Dairy intake - DDR -0.0189 0.0790 8.1E-01 472 0.1913 0.0757 1.2E-02 453 2.7E-02 Choline intake - FFQ Dairy intake - FFQ -0.0437 0.0799 5.8E-01 472 0.1946 0.0784 1.4E-02 453 2.9E-02 Choline intake - FFQ Egg intake - DDR 0.0139 0.0799 8.6E-01 472 0.1940 0.0796 1.5E-02 453 3.0E-02 Choline intake - FFQ Egg intake - FFQ -0.0708 0.0889 4.3E-01 472 0.2023 0.0897 2.5E-02 453 2.8E-02 Choline intake - FFQ Fish intake - DDR 0.0542 0.0748 4.7E-01 472 0.1990 0.0759 9.1E-03 453 3.3E-02 Choline intake - FFQ Fish intake - FFQ 0.0213 0.0763 7.8E-01 472 0.1807 0.0757 1.7E-02 453 3.4E-02 Choline intake - FFQ Plasma choline 0.0182 0.0770 8.1E-01 472 0.1704 0.0756 2.5E-02 453 4.1E-02 Choline intake - FFQ Plasma L-carnitine 0.0125 0.0773 8.7E-01 472 0.1671 0.0763 2.9E-02 453 2.7E-02 Choline intake - FFQ Red meat intake - DDR 0.0194 0.0778 8.0E-01 472 0.1425 0.0775 6.6E-02 453 3.8E-02 Choline intake - FFQ Red meat intake - FFQ 0.0429 0.0784 5.8E-01 472 0.1196 0.0810 1.4E-01 453 4.7E-02 Choline intake - DDR Fully adjusted 0.0536 0.0605 3.8E-01 472 0.1255 0.0549 2.3E-02 453 2.1E-01 Choline intake - DDR Choline intake - FFQ 0.0432 0.0670 5.2E-01 472 0.1037 0.0583 7.6E-02 453 1.8E-01 Choline intake - DDR Dairy intake - DDR 0.0391 0.0605 5.2E-01 472 0.1261 0.0549 2.2E-02 453 2.1E-01 Choline intake - DDR Dairy intake - FFQ 0.0312 0.0611 6.1E-01 472 0.1287 0.0556 2.1E-02 453 2.0E-01 Choline intake - DDR Egg intake - DDR 0.0728 0.0832 3.8E-01 472 0.1826 0.0709 1.0E-02 453 2.4E-01 Choline intake - DDR Egg intake - FFQ 0.0297 0.0651 6.5E-01 472 0.1256 0.0566 2.7E-02 453 1.5E-01 Choline intake - DDR Fish intake - DDR 0.0580 0.0607 3.4E-01 472 0.1352 0.0553 1.5E-02 453 1.5E-01 Choline intake - DDR Fish intake - FFQ 0.0457 0.0609 4.5E-01 472 0.1400 0.0548 1.1E-02 453 1.1E-01 Choline intake - DDR Plasma choline 0.0537 0.0605 3.8E-01 472 0.1139 0.0550 3.9E-02 453 2.4E-01 Choline intake - DDR Plasma L-carnitine 0.0518 0.0605 3.9E-01 472 0.1143 0.0554 4.0E-02 453 2.6E-01 Choline intake - DDR Red meat intake - DDR 0.0495 0.0644 4.4E-01 472 0.0862 0.0595 1.5E-01 453 2.1E-01 Choline intake - DDR Red meat intake - FFQ 0.0683 0.0609 2.6E-01 472 0.1119 0.0558 4.5E-02 453 1.9E-01 Plasma choline Fully adjusted -0.0162 0.0495 7.4E-01 472 0.1098 0.0463 1.8E-02 453 4.2E-02 Plasma choline Choline intake - DDR -0.0168 0.0496 7.4E-01 472 0.0972 0.0464 3.7E-02 453 5.7E-02 Plasma choline Choline intake - FFQ -0.0150 0.0500 7.7E-01 472 0.1015 0.0468 3.1E-02 453 6.7E-02 Plasma choline Dairy intake - DDR -0.0267 0.0496 5.9E-01 472 0.1094 0.0463 1.9E-02 453 3.7E-02 34

Supplementary Data 2b Absence (species)/ Non- Presence (species)/ Dietary Exposure Additionally conditioned on producer (mixed score) TMAO-producer (mixed P-interaction Effect Se P n Effect Se P n Plasma choline Dairy intake - FFQ -0.0258 0.0493 6.0E-01 472 0.1105 0.0464 1.8E-02 453 2.9E-02 Plasma choline Egg intake - DDR -0.0156 0.0496 7.5E-01 472 0.1084 0.0468 2.1E-02 453 4.8E-02 Plasma choline Egg intake - FFQ -0.0160 0.0494 7.5E-01 472 0.1073 0.0466 2.2E-02 453 5.6E-02 Plasma choline Fish intake - DDR -0.0157 0.0485 7.5E-01 472 0.1016 0.0465 3.0E-02 453 6.8E-02 Plasma choline Fish intake - FFQ -0.0112 0.0498 8.2E-01 472 0.1019 0.0462 2.8E-02 453 6.2E-02 Plasma choline Plasma L-carnitine -0.0298 0.0517 5.6E-01 472 0.0960 0.0469 4.1E-02 453 3.5E-02 Plasma choline Red meat intake - DDR -0.0182 0.0497 7.1E-01 472 0.1011 0.0460 2.9E-02 453 4.9E-02 Plasma choline Red meat intake - FFQ -0.0186 0.0494 7.1E-01 472 0.1198 0.0464 1.0E-02 453 3.2E-02 Plasma L-carnitine Fully adjusted 0.0378 0.0485 4.4E-01 472 0.0859 0.0422 4.2E-02 453 4.1E-01 Plasma L-carnitine Choline intake - DDR 0.0378 0.0485 4.4E-01 472 0.0691 0.0427 1.1E-01 453 5.3E-01 Plasma L-carnitine Choline intake - FFQ 0.0368 0.0496 4.6E-01 472 0.0728 0.0431 9.2E-02 453 5.0E-01 Plasma L-carnitine Dairy intake - DDR 0.0218 0.0491 6.6E-01 472 0.0902 0.0424 3.4E-02 453 3.9E-01 Plasma L-carnitine Dairy intake - FFQ 0.0282 0.0483 5.6E-01 472 0.0857 0.0423 4.4E-02 453 3.9E-01 Plasma L-carnitine Egg intake - DDR 0.0375 0.0486 4.4E-01 472 0.0847 0.0423 4.6E-02 453 4.2E-01 Plasma L-carnitine Egg intake - FFQ 0.0284 0.0487 5.6E-01 472 0.0842 0.0423 4.7E-02 453 3.8E-01 Plasma L-carnitine Fish intake - DDR 0.0458 0.0476 3.4E-01 472 0.0742 0.0423 8.0E-02 453 6.4E-01 Plasma L-carnitine Fish intake - FFQ 0.0390 0.0484 4.2E-01 472 0.0849 0.0421 4.5E-02 453 4.2E-01 Plasma L-carnitine Plasma choline 0.0463 0.0507 3.6E-01 472 0.0703 0.0427 1.0E-01 453 3.8E-01 Plasma L-carnitine Red meat intake - DDR 0.0374 0.0487 4.4E-01 472 0.0609 0.0431 1.6E-01 453 4.9E-01 Plasma L-carnitine Red meat intake - FFQ 0.0407 0.0484 4.0E-01 472 0.0804 0.0420 5.6E-02 453 4.2E-01 Dairy intake - FFQ Fully adjusted 0.1030 0.0379 6.9E-03 472 0.0077 0.0355 8.3E-01 453 3.7E-01 Dairy intake - FFQ Choline intake - DDR 0.1038 0.0385 7.3E-03 472 -0.0108 0.0361 7.6E-01 453 3.6E-01 Dairy intake - FFQ Choline intake - FFQ 0.1064 0.0409 9.6E-03 472 -0.0138 0.0379 7.2E-01 453 4.9E-01 Dairy intake - FFQ Dairy intake - DDR 0.0939 0.0488 5.5E-02 472 0.0281 0.0404 4.9E-01 453 3.5E-01 Dairy intake - FFQ Egg intake - DDR 0.1024 0.0381 7.4E-03 472 0.0089 0.0356 8.0E-01 453 4.0E-01 Dairy intake - FFQ Egg intake - FFQ 0.0969 0.0381 1.1E-02 472 0.0072 0.0356 8.4E-01 453 4.2E-01 Dairy intake - FFQ Fish intake - DDR 0.1060 0.0382 5.7E-03 472 -0.0062 0.0356 8.6E-01 453 2.6E-01 Dairy intake - FFQ Fish intake - FFQ 0.1021 0.0379 7.3E-03 472 0.0124 0.0357 7.3E-01 453 4.2E-01 Dairy intake - FFQ Plasma choline 0.1045 0.0381 6.3E-03 472 0.0114 0.0354 7.5E-01 453 3.8E-01 Dairy intake - FFQ Plasma L-carnitine 0.1014 0.0381 8.0E-03 472 0.0024 0.0355 9.5E-01 453 3.7E-01 Dairy intake - FFQ Red meat intake - DDR 0.1032 0.0380 6.9E-03 472 0.0128 0.0353 7.2E-01 453 3.7E-01 Dairy intake - FFQ Red meat intake - FFQ 0.0976 0.0381 1.1E-02 472 0.0203 0.0360 5.7E-01 453 4.2E-01 Dairy intake - DDR Fully adjusted 0.0874 0.0369 1.8E-02 472 -0.0284 0.0360 4.3E-01 453 1.5E-01 Dairy intake - DDR Choline intake - DDR 0.0849 0.0371 2.3E-02 472 -0.0294 0.0358 4.1E-01 453 1.7E-01 Dairy intake - DDR Choline intake - FFQ 0.0930 0.0383 1.6E-02 472 -0.0273 0.0368 4.6E-01 453 1.9E-01 Dairy intake - DDR Dairy intake - FFQ 0.0542 0.0463 2.4E-01 472 -0.0330 0.0390 4.0E-01 453 1.9E-01 Dairy intake - DDR Egg intake - DDR 0.0883 0.0370 1.7E-02 472 -0.0268 0.0362 4.6E-01 453 1.6E-01 Dairy intake - DDR Egg intake - FFQ 0.0857 0.0371 2.1E-02 472 -0.0266 0.0362 4.6E-01 453 2.0E-01 Dairy intake - DDR Fish intake - DDR 0.0869 0.0369 1.9E-02 472 -0.0326 0.0361 3.7E-01 453 1.2E-01 Dairy intake - DDR Fish intake - FFQ 0.0884 0.0369 1.7E-02 472 -0.0439 0.0361 2.2E-01 453 1.2E-01 Dairy intake - DDR Plasma choline 0.0877 0.0370 1.8E-02 472 -0.0231 0.0359 5.2E-01 453 1.7E-01 Dairy intake - DDR Plasma L-carnitine 0.0832 0.0375 2.7E-02 472 -0.0323 0.0359 3.7E-01 453 1.7E-01 Dairy intake - DDR Red meat intake - DDR 0.0920 0.0371 1.3E-02 472 -0.0182 0.0360 6.1E-01 453 1.7E-01 Dairy intake - DDR Red meat intake - FFQ 0.0866 0.0370 2.0E-02 472 -0.0197 0.0361 5.9E-01 453 1.7E-01 Egg intake - FFQ Fully adjusted 0.2162 0.1204 7.3E-02 472 0.0811 0.1100 4.6E-01 453 9.4E-01 Egg intake - FFQ Choline intake - DDR 0.2309 0.1290 7.4E-02 472 0.0342 0.1111 7.6E-01 453 9.1E-01 Egg intake - FFQ Choline intake - FFQ 0.2842 0.1446 5.0E-02 472 -0.0418 0.1320 7.5E-01 453 8.8E-01 Egg intake - FFQ Dairy intake - DDR 0.1940 0.1208 1.1E-01 472 0.0751 0.1103 5.0E-01 453 9.8E-01 Egg intake - FFQ Dairy intake - FFQ 0.1839 0.1204 1.3E-01 472 0.0806 0.1102 4.6E-01 453 9.7E-01 Egg intake - FFQ Egg intake - DDR 0.2594 0.1413 6.7E-02 472 0.0676 0.1196 5.7E-01 453 9.3E-01 Egg intake - FFQ Fish intake - DDR 0.1881 0.1208 1.2E-01 472 0.0530 0.1106 6.3E-01 453 9.3E-01 Egg intake - FFQ Fish intake - FFQ 0.2147 0.1203 7.5E-02 472 0.0896 0.1101 4.2E-01 453 9.8E-01 Egg intake - FFQ Plasma choline 0.2161 0.1206 7.4E-02 472 0.0520 0.1102 6.4E-01 453 8.7E-01 Egg intake - FFQ Plasma L-carnitine 0.2083 0.1213 8.7E-02 472 0.0669 0.1099 5.4E-01 453 9.9E-01 Egg intake - FFQ Red meat intake - DDR 0.2198 0.1212 7.0E-02 472 0.0388 0.1101 7.2E-01 453 8.9E-01 Egg intake - FFQ Red meat intake - FFQ 0.2115 0.1202 7.9E-02 472 0.0361 0.1140 7.5E-01 453 9.7E-01 Egg intake - DDR Fully adjusted 0.0364 0.0944 7.0E-01 472 0.0385 0.0824 6.4E-01 453 5.7E-01 35

Supplementary Data 2b Absence (species)/ Non- Presence (species)/ Dietary Exposure Additionally conditioned on producer (mixed score) TMAO-producer (mixed P-interaction Effect Se P n Effect Se P n Egg intake - DDR Choline intake - DDR -0.0381 0.1271 7.6E-01 472 -0.1343 0.1059 2.1E-01 453 5.1E-01 Egg intake - DDR Choline intake - FFQ 0.0083 0.1014 9.3E-01 472 -0.0123 0.0872 8.9E-01 453 4.6E-01 Egg intake - DDR Dairy intake - DDR 0.0475 0.0940 6.1E-01 472 0.0314 0.0830 7.1E-01 453 5.6E-01 Egg intake - DDR Dairy intake - FFQ 0.0127 0.0942 8.9E-01 472 0.0384 0.0825 6.4E-01 453 4.6E-01 Egg intake - DDR Egg intake - FFQ -0.0515 0.1111 6.4E-01 472 0.0246 0.0898 7.8E-01 453 4.3E-01 Egg intake - DDR Fish intake - DDR 0.0345 0.0945 7.1E-01 472 0.0444 0.0829 5.9E-01 453 5.3E-01 Egg intake - DDR Fish intake - FFQ 0.0267 0.0944 7.8E-01 472 0.0320 0.0821 7.0E-01 453 5.0E-01 Egg intake - DDR Plasma choline 0.0365 0.0945 7.0E-01 472 0.0142 0.0828 8.6E-01 453 6.5E-01 Egg intake - DDR Plasma L-carnitine 0.0342 0.0944 7.2E-01 472 0.0310 0.0823 7.1E-01 453 5.8E-01 Egg intake - DDR Red meat intake - DDR 0.0553 0.0965 5.7E-01 472 0.0052 0.0831 9.5E-01 453 7.5E-01 Egg intake - DDR Red meat intake - FFQ 0.0530 0.0954 5.8E-01 472 0.0265 0.0828 7.5E-01 453 5.0E-01 Fish intake - FFQ Fully adjusted 0.4960 0.2091 1.8E-02 472 0.4603 0.1643 5.3E-03 453 5.5E-01 Fish intake - FFQ Choline intake - DDR 0.4891 0.2107 2.1E-02 472 0.5127 0.1646 2.0E-03 453 7.6E-01 Fish intake - FFQ Choline intake - FFQ 0.4996 0.2234 2.6E-02 472 0.4982 0.1718 3.9E-03 453 7.9E-01 Fish intake - FFQ Dairy intake - DDR 0.5149 0.2087 1.4E-02 472 0.4685 0.1645 4.6E-03 453 5.1E-01 Fish intake - FFQ Dairy intake - FFQ 0.4966 0.2077 1.7E-02 472 0.4685 0.1661 5.0E-03 453 6.4E-01 Fish intake - FFQ Egg intake - DDR 0.4951 0.2096 1.9E-02 472 0.4601 0.1644 5.4E-03 453 5.6E-01 Fish intake - FFQ Egg intake - FFQ 0.5195 0.2091 1.3E-02 472 0.4742 0.1652 4.3E-03 453 6.2E-01 Fish intake - FFQ Fish intake - DDR 0.4600 0.2241 4.1E-02 472 0.4489 0.1691 8.2E-03 453 6.6E-01 Fish intake - FFQ Plasma choline 0.4867 0.2134 2.3E-02 472 0.4718 0.1636 4.1E-03 453 4.7E-01 Fish intake - FFQ Plasma L-carnitine 0.5003 0.2093 1.7E-02 472 0.4897 0.1643 3.0E-03 453 6.4E-01 Fish intake - FFQ Red meat intake - DDR 0.4795 0.2115 2.4E-02 472 0.5504 0.1655 9.6E-04 453 7.3E-01 Fish intake - FFQ Red meat intake - FFQ 0.5168 0.2090 1.4E-02 472 0.5198 0.1648 1.7E-03 453 5.8E-01 Fish intake - DDR Fully adjusted 0.0483 0.0349 1.7E-01 472 0.0392 0.0333 2.4E-01 453 8.9E-01 Fish intake - DDR Choline intake - DDR 0.0379 0.0366 3.0E-01 472 0.0208 0.0339 5.4E-01 453 9.8E-01 Fish intake - DDR Choline intake - FFQ 0.0522 0.0358 1.5E-01 472 0.0476 0.0342 1.7E-01 453 9.3E-01 Fish intake - DDR Dairy intake - DDR 0.0588 0.0350 9.3E-02 472 0.0379 0.0333 2.6E-01 453 8.4E-01 Fish intake - DDR Dairy intake - FFQ 0.0528 0.0348 1.3E-01 472 0.0391 0.0334 2.4E-01 453 8.9E-01 Fish intake - DDR Egg intake - DDR 0.0479 0.0350 1.7E-01 472 0.0401 0.0333 2.3E-01 453 9.2E-01 Fish intake - DDR Egg intake - FFQ 0.0441 0.0350 2.1E-01 472 0.0413 0.0335 2.2E-01 453 9.5E-01 Fish intake - DDR Fish intake - FFQ 0.0244 0.0374 5.1E-01 472 0.0210 0.0340 5.4E-01 453 9.6E-01 Fish intake - DDR Plasma choline 0.0482 0.0351 1.7E-01 472 0.0454 0.0333 1.7E-01 453 8.7E-01 Fish intake - DDR Plasma L-carnitine 0.0506 0.0349 1.5E-01 472 0.0377 0.0332 2.6E-01 453 8.3E-01 Fish intake - DDR Red meat intake - DDR 0.0424 0.0352 2.3E-01 472 0.0487 0.0333 1.4E-01 453 9.5E-01 Fish intake - DDR Red meat intake - FFQ 0.0463 0.0349 1.9E-01 472 0.0489 0.0338 1.5E-01 453 9.0E-01

Supplementary Data 2c Supplementary Data 2c. Associations of intakes of choline and red meat, or other TMAO precursors with TMAO levels, stratified by TMAO- producer phenotype, in 6 different sensitivity analysis models. Basic model included basic necessary variables including age, antibiotics use, probiotics use, the Bristol Stool Chart, and/or fish intake (for non-fish dietary variables). Full model (MV) was based on basic model and further adjusted for BMI, physical activity, energy intake, smoking, cumulative dietary quality. DM, diabetes mellitus. TMAO Non-producer TMAO-producer (mixed P- Dietary Exposure Sensitivity analysis model (mixed score) score) interaction Effect Se P n Effect Se P n Red meat intake - FFQ MV + renal function indicator -0.1599 0.1039 1.2E-01 472 0.1936 0.0839 2.1E-02 453 4.2E-03 Red meat intake - FFQ MV & Exclude DM patients -0.1917 0.1039 6.6E-02 458 0.1936 0.0884 2.9E-02 425 1.6E-03 Red meat intake - FFQ MV + pre-DM and DM status -0.1862 0.1023 6.9E-02 472 0.1959 0.0849 2.2E-02 453 3.1E-03 Red meat intake - FFQ MV + HBA1c -0.1957 0.1014 5.4E-02 472 0.1834 0.0845 3.1E-02 453 3.3E-03 Red meat intake - FFQ MV + FFQ phosphorus intake -0.1680 0.1069 1.2E-01 472 0.2328 0.0859 7.0E-03 453 2.1E-03 Red meat intake - FFQ Basic Model -0.1917 0.0845 2.4E-02 472 0.1146 0.0665 8.5E-02 453 5.9E-03 Red meat intake - DDR (default-5d avg) MV + renal function indicator 0.0248 0.0271 3.6E-01 472 0.0658 0.0250 8.7E-03 453 1.3E-01 Red meat intake - DDR (default-5d avg) MV & Exclude DM patients 0.0194 0.0270 4.7E-01 458 0.0724 0.0264 6.3E-03 425 7.6E-02 Red meat intake - DDR (default-5d avg) MV + pre-DM and DM status 0.0121 0.0266 6.5E-01 472 0.0620 0.0254 1.5E-02 453 1.1E-01 Red meat intake - DDR (default-5d avg) MV + HBA1c 0.0111 0.0265 6.8E-01 472 0.0592 0.0254 2.0E-02 453 1.4E-01 Red meat intake - DDR (default-5d avg) MV + DDR (5d avg) phosphorus intake 0.0069 0.0269 8.0E-01 472 0.0607 0.0254 1.7E-02 453 1.0E-01 Red meat intake - DDR (default-5d avg) Basic Model -0.0014 0.0248 9.5E-01 472 0.0622 0.0237 9.1E-03 453 1.1E-01 Red meat intake - DDR (sensitivity -2d avg) MV + renal function indicator 0.0315 0.0220 1.5E-01 472 0.0580 0.0200 3.8E-03 453 1.8E-01 Red meat intake - DDR (sensitivity -2d avg) MV & Exclude DM patients 0.0255 0.0222 2.5E-01 458 0.0606 0.0210 4.2E-03 425 1.4E-01 Red meat intake - DDR (sensitivity -2d avg) MV + pre-DM and DM status 0.0264 0.0218 2.3E-01 472 0.0516 0.0202 1.1E-02 453 2.5E-01 Red meat intake - DDR (sensitivity -2d avg) MV + HBA1c 0.0258 0.0217 2.4E-01 472 0.0502 0.0202 1.3E-02 453 2.8E-01 Red meat intake - DDR (sensitivity -2d avg) MV + DDR (2d avg) phosphorus intake 0.0250 0.0219 2.5E-01 472 0.0487 0.0204 1.8E-02 453 3.1E-01 Red meat intake - DDR (sensitivity -2d avg) Basic Model 0.0021 0.0205 9.2E-01 472 0.0498 0.0193 1.0E-02 453 1.5E-01 Choline intake - FFQ MV + renal function indicator 0.0402 0.0776 6.0E-01 472 0.1785 0.0749 1.8E-02 453 5.5E-02 Choline intake - FFQ MV & Exclude DM patients 0.0360 0.0764 6.4E-01 458 0.2200 0.0795 5.9E-03 425 2.1E-02 Choline intake - FFQ MV + pre-DM and DM status 0.0231 0.0765 7.6E-01 472 0.2080 0.0767 7.0E-03 453 2.6E-02 Choline intake - FFQ MV + HBA1c 0.0183 0.0759 8.1E-01 472 0.1963 0.0753 9.4E-03 453 3.0E-02 Choline intake - FFQ MV + FFQ phosphorus intake -0.0500 0.0964 6.0E-01 472 0.1072 0.0923 2.5E-01 453 3.9E-02 Choline intake - FFQ Basic Model -0.0227 0.0502 6.5E-01 472 0.0686 0.0428 1.1E-01 453 1.5E-01 Choline intake - DDR (default-5d avg) MV + renal function indicator 0.0735 0.0611 2.3E-01 472 0.1266 0.0542 2.0E-02 453 2.6E-01 Choline intake - DDR (default-5d avg) MV & Exclude DM patients 0.0802 0.0606 1.9E-01 458 0.1442 0.0567 1.1E-02 425 3.1E-01 Choline intake - DDR (default-5d avg) MV + pre-DM and DM status 0.0574 0.0603 3.4E-01 472 0.1251 0.0550 2.4E-02 453 2.2E-01 Choline intake - DDR (default-5d avg) MV + HBA1c 0.0587 0.0598 3.3E-01 472 0.1258 0.0548 2.2E-02 453 2.7E-01 Choline intake - DDR (default-5d avg) MV + DDR (5d avg) phosphorus intake -0.0083 0.0682 9.0E-01 472 0.1233 0.0592 3.8E-02 453 2.5E-01 Choline intake - DDR (default-5d avg) Basic Model 0.0281 0.0481 5.6E-01 472 0.0985 0.0431 2.3E-02 453 2.6E-01 Choline intake - DDR (sensitivity -2d avg) MV + renal function indicator 0.0358 0.0629 5.7E-01 472 0.1382 0.0491 5.1E-03 453 8.2E-02 Choline intake - DDR (sensitivity -2d avg) MV & Exclude DM patients 0.0334 0.0625 5.9E-01 458 0.1599 0.0526 2.5E-03 425 6.9E-02 Choline intake - DDR (sensitivity -2d avg) MV + pre-DM and DM status 0.0302 0.0623 6.3E-01 472 0.1353 0.0500 7.0E-03 453 6.4E-02 Choline intake - DDR (sensitivity -2d avg) MV + HBA1c 0.0305 0.0619 6.2E-01 472 0.1390 0.0497 5.4E-03 453 8.4E-02 Choline intake - DDR (sensitivity -2d avg) MV + DDR (2d avg) phosphorus intake -0.0409 0.0679 5.5E-01 472 0.1320 0.0531 1.3E-02 453 4.7E-02 Choline intake - DDR (sensitivity -2d avg) Basic Model -0.0077 0.0502 8.8E-01 472 0.1040 0.0414 1.2E-02 453 1.2E-01 Plasma choline MV + renal function indicator -0.0287 0.0502 5.7E-01 472 0.0889 0.0463 5.5E-02 453 3.8E-02 Plasma choline MV & Exclude DM patients -0.0212 0.0497 6.7E-01 458 0.1135 0.0478 1.8E-02 425 2.9E-02 Plasma choline MV + pre-DM and DM status -0.0095 0.0495 8.5E-01 472 0.1079 0.0464 2.0E-02 453 5.1E-02 Plasma choline MV + HBA1c -0.0116 0.0489 8.1E-01 472 0.1072 0.0461 2.1E-02 453 5.5E-02 Plasma choline MV + FFQ phosphorus intake -0.0172 0.0500 7.3E-01 472 0.1123 0.0464 1.6E-02 453 4.9E-02 Plasma choline Basic Model -0.0174 0.0490 7.2E-01 472 0.1022 0.0456 2.5E-02 453 3.6E-02 Plasma L-carnitine MV + renal function indicator 0.0408 0.0486 4.0E-01 472 0.0891 0.0417 3.3E-02 453 3.9E-01 Plasma L-carnitine MV & Exclude DM patients 0.0466 0.0490 3.4E-01 458 0.1226 0.0450 6.7E-03 425 1.8E-01 Plasma L-carnitine MV + pre-DM and DM status 0.0424 0.0483 3.8E-01 472 0.0974 0.0429 2.4E-02 453 3.5E-01 Plasma L-carnitine MV + HBA1c 0.0326 0.0479 5.0E-01 472 0.0912 0.0421 3.1E-02 453 2.9E-01 Plasma L-carnitine MV + FFQ phosphorus intake 0.0382 0.0494 4.4E-01 472 0.0744 0.0426 8.2E-02 453 5.5E-01 Plasma L-carnitine Basic Model 0.0542 0.0476 2.6E-01 472 0.0810 0.0411 5.0E-02 453 5.3E-01 Egg intake - FFQ MV + renal function indicator 0.2227 0.1206 6.6E-02 472 0.0860 0.1092 4.3E-01 453 9.7E-01 Egg intake - FFQ MV & Exclude DM patients 0.2533 0.1196 3.5E-02 458 0.1011 0.1135 3.7E-01 425 9.2E-01 Egg intake - FFQ MV + pre-DM and DM status 0.2133 0.1200 7.6E-02 472 0.0919 0.1105 4.1E-01 453 9.7E-01 Egg intake - FFQ MV + HBA1c 0.2110 0.1190 7.7E-02 472 0.0934 0.1098 4.0E-01 453 9.9E-01 Egg intake - FFQ MV + FFQ phosphorus intake 0.2097 0.1262 9.7E-02 472 0.1166 0.1106 2.9E-01 453 8.2E-01 Egg intake - FFQ Basic Model 0.1574 0.1133 1.7E-01 472 0.0694 0.1032 5.0E-01 453 6.6E-01 Egg intake - DDR (default-5d avg) MV + renal function indicator 0.0486 0.0958 6.1E-01 472 0.0093 0.0819 9.1E-01 453 7.1E-01 Egg intake - DDR (default-5d avg) MV & Exclude DM patients 0.0587 0.0947 5.4E-01 458 0.0599 0.0863 4.9E-01 425 6.0E-01 Egg intake - DDR (default-5d avg) MV + pre-DM and DM status 0.0422 0.0948 6.6E-01 472 0.0332 0.0827 6.9E-01 453 6.4E-01 Egg intake - DDR (default-5d avg) MV + HBA1c 0.0478 0.0933 6.1E-01 472 0.0358 0.0823 6.6E-01 453 7.0E-01 Egg intake - DDR (default-5d avg) MV + DDR (5d avg) phosphorus intake 0.0258 0.0948 7.9E-01 472 0.0427 0.0825 6.1E-01 453 5.2E-01 Egg intake - DDR (default-5d avg) Basic Model 0.0614 0.0937 5.1E-01 472 0.0576 0.0813 4.8E-01 453 8.0E-01 Egg intake - DDR (sensitivity -2d avg) MV + renal function indicator -0.0097 0.0757 9.0E-01 472 0.1427 0.0653 3.0E-02 453 6.9E-02 Egg intake - DDR (sensitivity -2d avg) MV & Exclude DM patients -0.0088 0.0752 9.1E-01 458 0.1960 0.0698 5.2E-03 425 3.2E-02 Egg intake - DDR (sensitivity -2d avg) MV + pre-DM and DM status -0.0050 0.0753 9.5E-01 472 0.1650 0.0661 1.3E-02 453 4.9E-02 Egg intake - DDR (sensitivity -2d avg) MV + HBA1c 0.0002 0.0747 1.0E+00 472 0.1697 0.0653 9.7E-03 453 6.3E-02 37

Supplementary Data 2c TMAO Non-producer TMAO-producer (mixed P- Dietary Exposure Sensitivity analysis model (mixed score) score) interaction Effect Se P n Effect Se P n Egg intake - DDR (sensitivity -2d avg) MV + DDR (2d avg) phosphorus intake -0.0081 0.0752 9.1E-01 472 0.1762 0.0654 7.3E-03 453 3.4E-02 Egg intake - DDR (sensitivity -2d avg) Basic Model 0.0037 0.0768 9.6E-01 472 0.1547 0.0647 1.7E-02 453 1.2E-01 Dairy intake - FFQ MV + renal function indicator 0.1094 0.0383 4.5E-03 472 0.0197 0.0353 5.8E-01 453 3.5E-01 Dairy intake - FFQ MV & Exclude DM patients 0.0839 0.0383 2.9E-02 458 0.0154 0.0371 6.8E-01 425 7.8E-01 Dairy intake - FFQ MV + pre-DM and DM status 0.0972 0.0379 1.1E-02 472 0.0156 0.0363 6.7E-01 453 4.1E-01 Dairy intake - FFQ MV + HBA1c 0.0881 0.0379 2.0E-02 472 0.0131 0.0355 7.1E-01 453 4.8E-01 Dairy intake - FFQ MV + FFQ phosphorus intake 0.1216 0.0502 1.6E-02 472 -0.0746 0.0456 1.0E-01 453 4.4E-01 Dairy intake - FFQ Basic Model 0.0556 0.0357 1.2E-01 472 -0.0010 0.0315 9.7E-01 453 2.0E-01 Dairy intake - DDR (default-5d avg) MV + renal function indicator 0.0959 0.0374 1.1E-02 472 -0.0182 0.0356 6.1E-01 453 1.7E-01 Dairy intake - DDR (default-5d avg) MV & Exclude DM patients 0.0702 0.0376 6.2E-02 458 -0.0223 0.0380 5.6E-01 425 3.6E-01 Dairy intake - DDR (default-5d avg) MV + pre-DM and DM status 0.0812 0.0369 2.8E-02 472 -0.0230 0.0368 5.3E-01 453 2.1E-01 Dairy intake - DDR (default-5d avg) MV + HBA1c 0.0731 0.0368 4.7E-02 472 -0.0213 0.0363 5.6E-01 453 2.6E-01 Dairy intake - DDR (default-5d avg) MV + DDR (5d avg) phosphorus intake 0.0515 0.0441 2.4E-01 472 -0.0473 0.0387 2.2E-01 453 2.0E-01 Dairy intake - DDR (default-5d avg) Basic Model 0.0327 0.0352 3.5E-01 472 -0.0233 0.0331 4.8E-01 453 2.2E-01 Dairy intake - DDR (sensitivity -2d avg) MV + renal function indicator 0.0727 0.0331 2.9E-02 472 -0.0015 0.0309 9.6E-01 453 3.1E-01 Dairy intake - DDR (sensitivity -2d avg) MV & Exclude DM patients 0.0714 0.0332 3.2E-02 458 -0.0016 0.0325 9.6E-01 425 3.7E-01 Dairy intake - DDR (sensitivity -2d avg) MV + pre-DM and DM status 0.0656 0.0328 4.6E-02 472 -0.0017 0.0317 9.6E-01 453 3.3E-01 Dairy intake - DDR (sensitivity -2d avg) MV + HBA1c 0.0631 0.0326 5.4E-02 472 -0.0016 0.0314 9.6E-01 453 3.7E-01 Dairy intake - DDR (sensitivity -2d avg) MV + DDR (2d avg) phosphorus intake 0.0342 0.0395 3.9E-01 472 -0.0205 0.0328 5.3E-01 453 4.3E-01 Dairy intake - DDR (sensitivity -2d avg) Basic Model 0.0293 0.0318 3.6E-01 472 -0.0072 0.0292 8.1E-01 453 2.8E-01 Fish intake - FFQ MV + renal function indicator 0.5746 0.2130 7.2E-03 472 0.4586 0.1624 5.0E-03 453 3.6E-01 Fish intake - FFQ MV & Exclude DM patients 0.5624 0.2108 7.9E-03 458 0.4724 0.1679 5.1E-03 425 4.9E-01 Fish intake - FFQ MV + pre-DM and DM status 0.5046 0.2083 1.6E-02 472 0.4797 0.1673 4.4E-03 453 7.9E-01 Fish intake - FFQ MV + HBA1c 0.5320 0.2070 1.0E-02 472 0.5149 0.1663 2.1E-03 453 8.1E-01 Fish intake - FFQ MV + FFQ phosphorus intake 0.4615 0.2229 3.9E-02 472 0.5457 0.1697 1.4E-03 453 9.6E-01 Fish intake - FFQ Basic Model 0.3915 0.1866 3.6E-02 472 0.3690 0.1540 1.7E-02 453 7.8E-01 Fish intake - DDR (default-5d avg) MV + renal function indicator 0.0584 0.0354 1.0E-01 472 0.0464 0.0329 1.6E-01 453 8.1E-01 Fish intake - DDR (default-5d avg) MV & Exclude DM patients 0.0595 0.0359 9.8E-02 458 0.0421 0.0342 2.2E-01 425 7.8E-01 Fish intake - DDR (default-5d avg) MV + pre-DM and DM status 0.0451 0.0347 1.9E-01 472 0.0408 0.0334 2.2E-01 453 9.7E-01 Fish intake - DDR (default-5d avg) MV + HBA1c 0.0483 0.0345 1.6E-01 472 0.0407 0.0333 2.2E-01 453 9.6E-01 Fish intake - DDR (default-5d avg) MV + DDR (5d avg) phosphorus intake 0.0295 0.0360 4.1E-01 472 0.0317 0.0342 3.5E-01 453 8.7E-01 Fish intake - DDR (default-5d avg) Basic Model 0.0461 0.0347 1.8E-01 472 0.0375 0.0330 2.6E-01 453 9.0E-01 Fish intake - DDR (sensitivity -2d avg) MV + renal function indicator 0.0383 0.0262 1.5E-01 472 0.0284 0.0253 2.6E-01 453 9.6E-01 Fish intake - DDR (sensitivity -2d avg) MV & Exclude DM patients 0.0337 0.0259 1.9E-01 458 0.0299 0.0262 2.5E-01 425 8.4E-01 Fish intake - DDR (sensitivity -2d avg) MV + pre-DM and DM status 0.0263 0.0258 3.1E-01 472 0.0302 0.0257 2.4E-01 453 6.4E-01 Fish intake - DDR (sensitivity -2d avg) MV + HBA1c 0.0275 0.0256 2.8E-01 472 0.0310 0.0256 2.3E-01 453 6.6E-01 Fish intake - DDR (sensitivity -2d avg) MV + DDR (2d avg) phosphorus intake 0.0116 0.0270 6.7E-01 472 0.0211 0.0266 4.3E-01 453 7.0E-01 Fish intake - DDR (sensitivity -2d avg) Basic Model 0.0338 0.0258 1.9E-01 472 0.0295 0.0255 2.5E-01 453 9.5E-01

Supplementary Data 2d Supplementary Data 2d. Associations of intakes of red meat with HDLC and HBA1c levels, stratified by TMAO-producer phenotype or TMAO-associated abundant species. Models were adjusted for age, BMI, physical activity, energy intake, refined carbohydrates intake, fiber intake, smoking, cumulative dietary quality, antibiotics use, probiotics use, the Bristol Stool Chart, and fish intake. Absence (species)/ Non- Presence (species)/ P- Stratified by Exposure Variable Outcome producer (mixed score) TMAO-producer (mixed interactio Taxa Stata Effect Se P n Effect Se P n n Red meat intake - FFQ Alistipes shahii Presence/Absence Plasma HDLC 0.2070 0.1976 3.0E-01 199 -0.0581 0.0783 4.6E-01 726 5.1E-03 Red meat intake - FFQ Alistipes shahii Presence/Absence Plasma HbA1c -0.2494 0.1931 2.0E-01 199 0.2934 0.0861 6.9E-04 726 1.2E-02 Red meat intake - FFQ Eubacterium biforme Presence/Absence Plasma HDLC -0.0743 0.0812 3.6E-01 699 0.1795 0.1509 2.4E-01 226 7.1E-02 Red meat intake - FFQ Eubacterium biforme Presence/Absence Plasma HbA1c 0.2072 0.0908 2.3E-02 699 0.1850 0.1502 2.2E-01 226 6.7E-01 Red meat intake - FFQ Eubacterium hallii Presence/Absence Plasma HDLC -0.2068 0.3282 5.3E-01 65 -0.0050 0.0750 9.5E-01 860 7.7E-01 Red meat intake - FFQ Eubacterium hallii Presence/Absence Plasma HbA1c 0.4156 0.3988 3.0E-01 65 0.2032 0.0811 1.2E-02 860 8.3E-01 Red meat intake - FFQ Roseburia hominis Presence/Absence Plasma HDLC -0.2856 0.2340 2.3E-01 103 0.0106 0.0768 8.9E-01 822 3.1E-01 Red meat intake - FFQ Roseburia hominis Presence/Absence Plasma HbA1c 0.6340 0.2710 2.2E-02 103 0.1670 0.0813 4.0E-02 822 1.3E-04 Red meat intake - FFQ TMAO-producer status Yes/No Plasma HDLC 0.0350 0.1106 7.5E-01 472 -0.0449 0.0957 6.4E-01 453 4.1E-01 Red meat intake - FFQ TMAO-producer status Yes/No Plasma HbA1c 0.1925 0.1155 9.6E-02 472 0.1651 0.1084 1.3E-01 453 6.5E-01

Supplementary Data 3a Supplementary Data 3a. Association of DNA gene clusters within TMAO-associated species with plasma TMAO levels, and intakes of choline and red meat. Full model was adjusted for age, BMI, physical activity, energy intake, smoking, cumulative dietary quality (since 1986), antibiotics use, probiotics use, the Bristol Stool Chart, and/or fish intake (for non-fish dietary variables). Red meat Red meat Choline intake- Choline UniRef90 Family Detection Plasma TMAO Species Cluster Name intake-FFQ intake-7DDR FFQ intake-7DDR member ID Rate Effect P FDR Effect P Effect P Effect P Effect P Alistipes_shahii UniRef90_D4IMG2 Cluster: Peptidase S24-like 0.64 0.00015 4.7E-04 2.0E-02 0.00001 9.2E-01 -0.00004 4.0E-01 0.00002 8.3E-01 0.00000 9.3E-01 Alistipes_shahii UniRef90_D4IKQ2 Cluster: Single-stranded DNA-binding protein 0.48 0.00011 3.6E-03 4.5E-02 -0.00012 6.4E-02 -0.00002 5.2E-01 -0.00013 6.1E-02 0.00000 9.3E-01 Alistipes_shahii UniRef90_D4IML2 Cluster: 50S ribosomal protein L36 0.58 0.00022 6.7E-03 5.4E-02 -0.00005 6.8E-01 -0.00013 1.1E-01 -0.00008 5.8E-01 -0.00003 7.7E-01 Alistipes_shahii UniRef90_I3YHV0 Cluster: 50S ribosomal protein L27 0.67 0.00012 6.6E-03 5.4E-02 -0.00002 7.9E-01 -0.00005 2.6E-01 -0.00008 3.1E-01 0.00001 9.1E-01 Alistipes_shahii UniRef90_I3YHU9 Cluster: 50S ribosomal protein L21 0.71 0.00012 6.5E-03 5.5E-02 0.00000 9.8E-01 -0.00004 4.2E-01 0.00000 9.8E-01 0.00001 9.1E-01 Alistipes_shahii UniRef90_D4IND3 Cluster: 50S ribosomal protein L33 0.64 0.00013 1.1E-02 7.6E-02 0.00004 5.9E-01 -0.00005 3.6E-01 0.00007 4.6E-01 0.00002 8.0E-01 Alistipes_shahii UniRef90_E4MCU7 Cluster: Transposase DDE domain 0.58 0.00021 2.3E-02 1.3E-01 -0.00040 1.5E-02 0.00004 6.9E-01 0.00027 1.4E-01 0.00009 4.1E-01 Alistipes_shahii UniRef90_D4ILS3 Cluster: 50S ribosomal protein L35 0.68 0.00011 2.6E-02 1.4E-01 0.00001 9.4E-01 -0.00004 3.6E-01 0.00001 9.2E-01 0.00002 7.6E-01 Alistipes_shahii UniRef90_D4IKQ0 Cluster: LPD11 domain-containing protein 0.45 0.00008 3.2E-02 1.6E-01 -0.00010 1.3E-01 -0.00001 7.7E-01 -0.00011 1.5E-01 -0.00005 3.0E-01 Alistipes_shahii UniRef90_D4IMJ9 Cluster: 50S ribosomal protein L29 0.66 0.00009 5.1E-02 2.1E-01 -0.00002 7.8E-01 -0.00006 2.3E-01 -0.00006 4.7E-01 -0.00004 5.2E-01 Alistipes_shahii UniRef90_D4IJV6 Cluster: Transposase DDE domain 0.57 0.00019 5.6E-02 2.2E-01 -0.00033 5.4E-02 0.00007 4.6E-01 0.00026 1.8E-01 0.00008 4.9E-01 Alistipes_shahii UniRef90_R7JL07 Cluster: 50S ribosomal protein L34 0.37 0.00012 6.6E-02 2.3E-01 -0.00001 9.1E-01 -0.00008 2.8E-01 -0.00015 1.9E-01 -0.00002 7.8E-01 Alistipes_shahii UniRef90_I3YR23 Cluster: Reverse transcriptase (RNA-dependent DNA polymerase) 0.76 0.00007 8.7E-02 2.8E-01 0.00001 8.7E-01 -0.00002 5.3E-01 0.00001 9.4E-01 0.00000 9.7E-01 Alistipes_shahii UniRef90_G5SRE3 Cluster: DUF4948 domain-containing protein 0.72 0.00004 1.7E-01 4.2E-01 -0.00002 7.3E-01 0.00002 4.7E-01 -0.00005 4.3E-01 0.00000 9.6E-01 Alistipes_shahii UniRef90_D4IL81 Cluster: YWFCY domain-containing protein 0.46 0.00008 1.9E-01 4.5E-01 0.00003 7.4E-01 0.00009 1.6E-01 -0.00011 3.0E-01 -0.00012 9.9E-02 Alistipes_shahii UniRef90_I3YM18 Cluster: 50S ribosomal protein L23 0.74 0.00005 2.2E-01 5.0E-01 -0.00001 9.3E-01 -0.00002 7.1E-01 -0.00008 3.2E-01 -0.00003 5.8E-01 Alistipes_shahii UniRef90_D4IKP8 Cluster: Resolvase, N terminal domain 0.49 0.00004 2.9E-01 5.9E-01 -0.00013 2.5E-02 -0.00002 5.4E-01 -0.00014 3.2E-02 -0.00004 3.6E-01 Alistipes_shahii UniRef90_I3YJW5 Cluster: Site-specific recombinase XerD 0.60 0.00007 3.9E-01 7.2E-01 0.00001 9.2E-01 -0.00001 8.6E-01 -0.00012 4.0E-01 -0.00019 4.0E-02 Alistipes_shahii UniRef90_I3YJF5 Cluster: Site-specific recombinase XerD 0.61 0.00005 4.1E-01 7.3E-01 -0.00014 1.1E-01 0.00000 9.7E-01 -0.00018 8.1E-02 -0.00010 1.4E-01 Alistipes_shahii UniRef90_G5SRG1 Cluster: Conjugative transposon protein TraI family protein 0.74 0.00002 5.2E-01 8.2E-01 -0.00012 3.1E-02 0.00004 2.1E-01 -0.00005 4.0E-01 -0.00004 3.1E-01 Alistipes_shahii UniRef90_A0A015U8H2 Cluster: Lce1l protein 0.69 0.00003 5.2E-01 8.2E-01 -0.00009 1.8E-01 -0.00001 7.2E-01 -0.00006 4.5E-01 0.00002 7.3E-01 Alistipes_shahii UniRef90_D4IN71 Cluster: Conjugative transposon TraJ protein 0.76 0.00002 5.3E-01 8.2E-01 -0.00013 1.3E-02 0.00002 5.2E-01 -0.00004 4.8E-01 -0.00003 3.5E-01 Alistipes_shahii UniRef90_G5SRF2 Cluster: DUF3408 domain-containing protein 0.73 0.00002 5.4E-01 8.3E-01 -0.00013 4.5E-02 -0.00001 8.3E-01 -0.00003 7.2E-01 -0.00001 8.9E-01 Alistipes_shahii UniRef90_D4IN34 Cluster: RteC protein 0.75 0.00002 5.5E-01 8.3E-01 -0.00014 1.8E-02 0.00001 7.2E-01 -0.00010 1.2E-01 -0.00005 2.5E-01 Alistipes_shahii UniRef90_G5SRE5 Cluster: Putative transmembrane protein 0.73 0.00002 6.0E-01 8.6E-01 -0.00009 1.5E-01 0.00001 8.4E-01 -0.00008 2.7E-01 0.00000 9.4E-01 Alistipes_shahii UniRef90_R9HZH5 Cluster: Conjugative transposon protein TraQ 0.75 0.00002 5.9E-01 8.6E-01 -0.00015 2.5E-02 0.00000 9.1E-01 -0.00008 2.7E-01 0.00000 9.6E-01 Alistipes_shahii UniRef90_A0A015U1S5 Cluster: MerR HTH regulatory family protein 0.73 -0.00001 7.3E-01 8.8E-01 -0.00016 2.4E-02 0.00002 6.9E-01 -0.00015 6.7E-02 -0.00001 8.4E-01 Alistipes_shahii UniRef90_A0A015U8I8 Cluster: DNA-binding protein 0.72 -0.00001 7.5E-01 8.9E-01 -0.00012 1.1E-01 -0.00002 6.9E-01 -0.00011 2.0E-01 -0.00007 1.9E-01 Alistipes_shahii UniRef90_D4IN63 Cluster: CbiA domain-containing protein 0.75 -0.00001 8.1E-01 9.2E-01 -0.00016 9.2E-03 0.00002 5.3E-01 -0.00004 5.8E-01 -0.00002 7.1E-01 Alistipes_shahii UniRef90_F9Z5Q9 Cluster: HTH luxR-type domain-containing protein 0.77 0.00001 8.1E-01 9.2E-01 -0.00002 8.4E-01 -0.00003 5.4E-01 -0.00006 4.8E-01 -0.00003 5.7E-01 Alistipes_shahii UniRef90_A0A015U1R7 Cluster: DNA-binding protein 0.72 0.00001 8.8E-01 9.6E-01 -0.00014 5.0E-02 0.00004 3.3E-01 -0.00006 4.5E-01 0.00001 9.2E-01 Alistipes_shahii UniRef90_F3PNI3 Cluster: Non-receptor tyrosine-protein kinase TNK1 0.73 0.00001 8.8E-01 9.6E-01 -0.00014 2.4E-02 0.00003 4.4E-01 -0.00015 3.1E-02 0.00003 5.0E-01 Alistipes_shahii unknown Unknown gene identity 0.78 0.00086 2.0E-03 3.9E-02 -0.00041 3.8E-01 -0.00017 5.4E-01 -0.00023 6.7E-01 -0.00002 9.4E-01 Alistipes_shahii UniRef90_R5W307 Uncharacterized protein 0.60 0.00015 2.7E-03 4.3E-02 -0.00003 6.8E-01 -0.00011 3.1E-02 0.00004 6.8E-01 -0.00005 3.8E-01 Alistipes_shahii UniRef90_D4IKP7 Cluster: Uncharacterized protein 0.49 0.00012 3.3E-03 4.5E-02 -0.00015 2.7E-02 -0.00002 6.1E-01 -0.00014 6.6E-02 -0.00002 7.0E-01 Alistipes_shahii UniRef90_D4IKQ5 Cluster: Uncharacterized protein 0.46 0.00011 3.9E-03 4.6E-02 -0.00006 3.8E-01 -0.00001 8.7E-01 -0.00010 1.6E-01 -0.00005 3.1E-01 Alistipes_shahii UniRef90_D4IIQ1 Cluster: Uncharacterized protein 0.30 0.00020 8.8E-03 6.6E-02 0.00013 1.8E-01 -0.00009 2.3E-01 0.00000 9.9E-01 -0.00003 7.0E-01 Alistipes_shahii UniRef90_D4IKQ4 Cluster: Uncharacterized protein 0.47 0.00009 9.2E-03 6.7E-02 -0.00013 2.4E-02 -0.00006 9.8E-02 -0.00009 1.7E-01 -0.00003 5.2E-01 Alistipes_shahii UniRef90_D4IKQ3 Cluster: Uncharacterized protein 0.44 0.00009 1.3E-02 8.3E-02 -0.00008 2.2E-01 -0.00006 1.3E-01 -0.00013 7.0E-02 -0.00007 1.3E-01 Alistipes_shahii UniRef90_D4IKQ6 Cluster: Uncharacterized protein 0.52 0.00012 2.4E-02 1.3E-01 -0.00001 9.5E-01 -0.00006 2.5E-01 -0.00003 7.5E-01 -0.00004 5.3E-01 Alistipes_shahii UniRef90_R5WAB6 Unknown - Obsolete ID 0.53 0.00012 2.9E-02 1.5E-01 0.00003 7.2E-01 0.00002 7.4E-01 0.00004 7.0E-01 0.00000 9.7E-01 Alistipes_shahii UniRef90_D4IIL0 Cluster: Uncharacterized protein 0.51 0.00012 4.0E-02 1.7E-01 -0.00007 3.9E-01 -0.00009 1.5E-01 -0.00002 8.2E-01 -0.00003 6.6E-01 Alistipes_shahii UniRef90_I9GMI8 Cluster: Uncharacterized protein 0.46 -0.00007 6.7E-02 2.3E-01 0.00008 2.2E-01 -0.00004 3.6E-01 0.00008 3.1E-01 0.00001 8.5E-01 Alistipes_shahii UniRef90_R5VXP6 Unknown - Obsolete ID 0.58 0.00009 9.8E-02 2.9E-01 0.00007 3.8E-01 0.00005 3.1E-01 0.00007 4.5E-01 -0.00005 4.1E-01 Alistipes_shahii UniRef90_D4INM5 Cluster: Uncharacterized protein 0.33 0.00006 1.3E-01 3.6E-01 -0.00008 2.2E-01 0.00000 9.1E-01 0.00003 6.7E-01 -0.00001 8.9E-01 Alistipes_shahii UniRef90_D4IKQ1 Cluster: Uncharacterized protein 0.47 0.00005 1.4E-01 3.8E-01 -0.00015 1.5E-02 -0.00004 2.3E-01 -0.00012 8.1E-02 -0.00007 1.1E-01 Alistipes_shahii UniRef90_A6L9Y5 Cluster: Uncharacterized protein 0.77 0.00004 1.6E-01 4.2E-01 -0.00002 7.5E-01 0.00002 5.7E-01 -0.00003 5.7E-01 -0.00001 8.8E-01 Alistipes_shahii UniRef90_R5W3D8 Unknown - Obsolete ID 0.30 0.00006 2.8E-01 5.9E-01 -0.00001 8.4E-01 0.00002 7.6E-01 -0.00015 1.1E-01 -0.00004 5.9E-01 Alistipes_shahii UniRef90_R5WBC9 Unknown - Obsolete ID 0.47 0.00006 3.2E-01 6.2E-01 -0.00004 6.3E-01 -0.00008 2.0E-01 0.00005 6.1E-01 0.00002 8.2E-01 Alistipes_shahii UniRef90_F7LPC9 Cluster: Uncharacterized protein 0.74 0.00004 4.1E-01 7.3E-01 -0.00001 8.9E-01 0.00005 2.9E-01 -0.00004 6.5E-01 -0.00001 8.3E-01 Alistipes_shahii UniRef90_I3YQU8 Cluster: Uncharacterized protein 0.74 0.00003 4.8E-01 8.0E-01 -0.00006 3.9E-01 0.00000 9.7E-01 0.00001 9.3E-01 -0.00005 3.2E-01 Alistipes_shahii UniRef90_A6L9Y6 Cluster: Uncharacterized protein 0.73 0.00003 5.0E-01 8.2E-01 0.00003 7.1E-01 0.00000 9.7E-01 0.00005 5.0E-01 0.00002 7.1E-01 Alistipes_shahii UniRef90_G5SRG4 Cluster: Uncharacterized protein 0.69 0.00003 5.2E-01 8.2E-01 -0.00007 2.7E-01 0.00002 6.0E-01 -0.00005 5.1E-01 -0.00009 4.5E-02 Alistipes_shahii UniRef90_A0A015V734 Cluster: Uncharacterized protein 0.71 0.00003 5.3E-01 8.2E-01 -0.00014 7.0E-02 -0.00001 8.2E-01 -0.00008 3.7E-01 0.00002 7.8E-01 Alistipes_shahii UniRef90_C9KRJ6 Cluster: Uncharacterized protein 0.68 -0.00002 5.8E-01 8.6E-01 -0.00013 5.2E-02 0.00000 9.5E-01 -0.00007 3.8E-01 -0.00003 5.0E-01 Alistipes_shahii UniRef90_A0A015VYS0 Cluster: Uncharacterized protein 0.76 -0.00002 6.0E-01 8.6E-01 -0.00012 2.6E-02 0.00001 6.7E-01 -0.00009 1.6E-01 -0.00001 7.3E-01 Alistipes_shahii UniRef90_Q5LEK6 Cluster: Uncharacterized protein 0.68 -0.00002 6.8E-01 8.6E-01 -0.00016 1.9E-02 -0.00005 1.9E-01 -0.00002 8.1E-01 -0.00002 6.7E-01 Alistipes_shahii UniRef90_D4IQI9 Cluster: Uncharacterized protein 0.75 0.00002 6.8E-01 8.7E-01 0.00001 8.9E-01 0.00005 2.6E-01 0.00007 3.8E-01 -0.00004 3.5E-01 Alistipes_shahii UniRef90_A0A015VYR6 Cluster: Uncharacterized protein 0.69 0.00002 7.0E-01 8.7E-01 -0.00023 2.2E-02 0.00006 3.5E-01 -0.00002 8.7E-01 -0.00001 9.3E-01 Alistipes_shahii UniRef90_I3YQU4 Cluster: Uncharacterized protein 0.77 0.00001 6.7E-01 8.7E-01 -0.00005 4.4E-01 0.00000 9.2E-01 -0.00003 6.7E-01 -0.00003 4.8E-01 Alistipes_shahii UniRef90_E5X4D0 Cluster: Uncharacterized protein 0.73 -0.00002 7.1E-01 8.7E-01 -0.00009 1.9E-01 0.00004 3.3E-01 -0.00007 3.8E-01 -0.00004 4.3E-01 40

Supplementary Data 3a Red meat Red meat Choline intake- Choline UniRef90 Family Detection Plasma TMAO Species Cluster Name intake-FFQ intake-7DDR FFQ intake-7DDR member ID Rate Effect P FDR Effect P Effect P Effect P Effect P Alistipes_shahii UniRef90_G5SRF4 Cluster: Uncharacterized protein 0.75 0.00002 6.4E-01 8.8E-01 -0.00013 1.9E-02 0.00000 9.0E-01 -0.00009 1.4E-01 -0.00004 3.0E-01 Alistipes_shahii UniRef90_G5SRI0 Cluster: Uncharacterized protein 0.69 0.00002 6.7E-01 8.8E-01 -0.00018 7.6E-03 -0.00002 6.0E-01 -0.00012 1.0E-01 -0.00003 5.2E-01 Alistipes_shahii UniRef90_D4IN61 Cluster: Uncharacterized protein 0.76 -0.00001 7.7E-01 9.0E-01 -0.00010 7.4E-02 0.00002 4.6E-01 -0.00006 3.8E-01 -0.00003 4.5E-01 Alistipes_shahii UniRef90_G5SRH1 Cluster: Uncharacterized protein 0.73 0.00001 8.7E-01 9.5E-01 -0.00015 2.0E-02 0.00001 7.7E-01 -0.00006 4.0E-01 -0.00002 6.9E-01 Alistipes_shahii UniRef90_G5SRF6 Cluster: Uncharacterized protein 0.70 -0.00001 8.8E-01 9.6E-01 -0.00013 2.8E-02 0.00002 6.2E-01 -0.00001 9.3E-01 -0.00004 3.5E-01 Alistipes_shahii UniRef90_G5SRE9 Cluster: Uncharacterized protein 0.73 0.00000 9.7E-01 9.9E-01 -0.00016 1.6E-02 0.00000 9.4E-01 -0.00008 2.9E-01 -0.00003 5.4E-01 Alistipes_shahii UniRef90_B3CC48 Cluster: Uncharacterized protein 0.71 0.00000 9.9E-01 1.0E+00 -0.00014 3.4E-02 0.00001 8.9E-01 -0.00008 3.0E-01 -0.00004 3.9E-01 Clostridiales_bacterium_1_7_47FAA unknown Unknown gene identity 0.19 0.00032 4.4E-03 4.5E-02 0.00008 6.1E-01 0.00010 3.7E-01 -0.00009 6.2E-01 0.00007 5.8E-01 Clostridiales_bacterium_1_7_47FAA UniRef90_C5EWS2 Cluster: Uncharacterized protein 0.19 0.00030 4.6E-03 4.7E-02 0.00001 9.3E-01 0.00002 8.3E-01 -0.00009 6.1E-01 0.00013 3.0E-01 Clostridiales_bacterium_1_7_47FAA UniRef90_UPI0001A5D2EF Unknown - Obsolete ID 0.19 0.00019 6.9E-03 5.4E-02 0.00002 8.5E-01 0.00003 6.3E-01 -0.00002 8.9E-01 0.00006 4.5E-01 Clostridiales_bacterium_1_7_47FAA UniRef90_C5ER98 Cluster: Uncharacterized protein 0.19 0.00015 2.4E-02 1.3E-01 0.00003 7.6E-01 0.00000 9.8E-01 -0.00010 3.9E-01 0.00007 3.6E-01 Clostridiales_bacterium_1_7_47FAA UniRef90_C5ER70 Cluster: Uncharacterized protein 0.19 0.00019 3.8E-02 1.7E-01 -0.00001 9.2E-01 0.00003 7.6E-01 -0.00019 2.1E-01 0.00003 7.7E-01 Clostridium_citroniae unknown Unknown gene identity 0.16 0.00022 7.2E-02 2.5E-01 -0.00031 6.8E-02 -0.00014 2.5E-01 -0.00003 8.8E-01 -0.00009 5.1E-01 Clostridium_clostridioforme unknown Unknown gene identity 0.11 0.00072 2.0E-04 2.5E-02 0.00032 3.2E-01 -0.00002 9.2E-01 0.00004 9.2E-01 0.00000 9.9E-01 Clostridium_nexile unknown Unknown gene identity 0.14 -0.00061 9.6E-03 6.9E-02 0.00029 4.4E-01 -0.00013 5.8E-01 0.00012 7.8E-01 -0.00011 6.8E-01 Clostridium_nexile UniRef90_C0WA78 Cluster: Uncharacterized protein 0.14 -0.00016 1.4E-02 8.4E-02 0.00001 9.0E-01 -0.00007 3.2E-01 -0.00002 8.8E-01 -0.00007 3.6E-01 Clostridium_nexile UniRef90_B6FQE5 Unknown - Obsolete ID 0.14 -0.00012 4.0E-02 1.8E-01 0.00004 6.6E-01 -0.00006 2.7E-01 0.00001 9.5E-01 -0.00004 5.6E-01 Clostridium_nexile UniRef90_B6FNZ3 Unknown - Obsolete ID 0.14 -0.00013 5.2E-02 2.1E-01 -0.00006 5.2E-01 -0.00009 1.7E-01 -0.00002 8.7E-01 -0.00011 1.5E-01 Clostridium_nexile UniRef90_B6FT19 Unknown - Obsolete ID 0.14 -0.00022 6.1E-02 2.3E-01 0.00004 8.0E-01 -0.00014 2.3E-01 0.00011 6.0E-01 -0.00003 8.0E-01 Clostridium_nexile UniRef90_B6FNJ3 Unknown - Obsolete ID 0.14 -0.00013 6.5E-02 2.3E-01 0.00006 5.9E-01 -0.00008 3.0E-01 0.00004 7.6E-01 -0.00009 3.0E-01 Clostridium_nexile UniRef90_T4GR84 Unknown - Obsolete ID 0.14 -0.00016 6.3E-02 2.3E-01 0.00006 6.4E-01 -0.00010 2.5E-01 0.00013 4.1E-01 -0.00001 9.0E-01 Clostridium_nexile UniRef90_B6FNP9 Unknown - Obsolete ID 0.14 -0.00009 8.5E-02 2.7E-01 0.00003 6.9E-01 -0.00008 1.6E-01 0.00004 6.5E-01 -0.00005 4.1E-01 Clostridium_nexile UniRef90_E5XIJ6 Cluster: Uncharacterized protein 0.14 -0.00014 1.4E-01 3.7E-01 0.00012 4.1E-01 -0.00011 2.3E-01 0.00019 2.6E-01 -0.00011 3.0E-01 Clostridium_nexile UniRef90_A0A023WJZ7 Unknown - Obsolete ID 0.14 -0.00011 2.2E-01 5.0E-01 0.00002 8.8E-01 -0.00005 5.6E-01 -0.00001 9.5E-01 -0.00010 3.4E-01 Clostridium_nexile UniRef90_E9RX65 Cluster: Uncharacterized protein 0.14 -0.00010 2.9E-01 5.9E-01 -0.00003 8.4E-01 -0.00007 4.6E-01 -0.00002 9.1E-01 -0.00015 1.9E-01 Erysipelotrichaceae_bacterium_21_3 unknown Unknown gene identity 0.12 0.00016 6.5E-02 2.3E-01 0.00004 7.4E-01 -0.00015 7.8E-02 -0.00002 8.8E-01 -0.00002 8.1E-01 Eubacterium_biforme UniRef90_W1I5J3 Cluster: Addiction module toxin, RelE/StbE family 0.17 -0.00021 4.9E-05 9.2E-03 -0.00018 3.3E-02 0.00007 1.7E-01 -0.00007 4.9E-01 -0.00007 2.4E-01 Eubacterium_biforme UniRef90_W1I4A6 Cluster: Uncultured bacterium extrachromosomal DNA RGI00018 0.17 -0.00020 3.1E-05 1.2E-02 -0.00022 7.8E-03 0.00006 1.9E-01 -0.00014 1.4E-01 -0.00009 1.2E-01 Eubacterium_biforme UniRef90_B7CE06 Cluster: Putative transposase DNA-binding domain protein (Fragment) 0.22 -0.00018 2.8E-03 4.3E-02 -0.00001 9.5E-01 0.00013 3.0E-02 -0.00001 9.4E-01 -0.00003 7.1E-01 Eubacterium_biforme UniRef90_B7CEA5 Cluster: Transposase 0.24 -0.00010 3.5E-02 1.7E-01 -0.00005 5.6E-01 0.00016 1.2E-03 -0.00003 7.7E-01 0.00000 9.7E-01 Eubacterium_biforme UniRef90_B7CBS9 Cluster: Zn_Tnp_IS91 domain-containing protein 0.23 -0.00012 3.7E-02 1.7E-01 -0.00009 4.0E-01 0.00010 1.1E-01 -0.00001 9.5E-01 -0.00001 9.0E-01 Eubacterium_biforme UniRef90_B7CEC8 Cluster: Transposase, IS4 family 0.21 -0.00009 5.2E-02 2.1E-01 -0.00004 5.9E-01 0.00008 1.1E-01 0.00003 7.6E-01 0.00001 9.2E-01 Eubacterium_biforme UniRef90_B7C9C6 Cluster: RNA-directed DNA polymerase 0.24 -0.00006 1.5E-01 3.9E-01 -0.00015 4.0E-02 0.00006 1.8E-01 0.00001 9.0E-01 -0.00008 1.3E-01 Eubacterium_biforme UniRef90_B7CEA2 Cluster: Transposase 0.20 -0.00008 1.6E-01 4.1E-01 -0.00005 5.9E-01 0.00009 1.0E-01 0.00011 3.0E-01 0.00002 8.0E-01 Eubacterium_biforme UniRef90_D4K8M7 Cluster: Group II intron reverse transcriptase/maturase 0.24 -0.00006 1.7E-01 4.2E-01 -0.00018 1.4E-02 0.00003 4.5E-01 0.00002 7.6E-01 -0.00008 1.0E-01 Eubacterium_biforme UniRef90_D4JA99 Cluster: HTH_17 domain-containing protein 0.23 -0.00004 3.1E-01 6.0E-01 -0.00001 8.5E-01 0.00006 1.5E-01 0.00000 9.9E-01 0.00001 8.5E-01 Eubacterium_biforme UniRef90_B7C756 Cluster: Uncharacterized protein (Fragment) 0.23 -0.00022 3.9E-04 2.1E-02 -0.00011 2.9E-01 0.00018 2.6E-03 -0.00004 7.2E-01 -0.00009 2.1E-01 Eubacterium_biforme unknown Unknown gene identity 0.24 -0.00047 5.5E-03 4.9E-02 -0.00032 2.7E-01 0.00036 3.1E-02 -0.00003 9.2E-01 -0.00013 5.1E-01 Eubacterium_biforme UniRef90_B7CED1 Cluster: Uncharacterized protein 0.21 -0.00015 1.1E-02 7.6E-02 -0.00006 5.6E-01 0.00007 2.3E-01 0.00007 5.6E-01 0.00002 8.0E-01 Eubacterium_biforme UniRef90_W1I1K8 Cluster: Uncharacterized protein 0.22 -0.00023 1.3E-02 8.2E-02 -0.00012 4.4E-01 0.00019 3.3E-02 0.00003 8.8E-01 -0.00001 8.9E-01 Eubacterium_biforme UniRef90_B7CDK1 Cluster: Uncharacterized protein 0.17 -0.00010 6.3E-02 2.3E-01 -0.00009 2.8E-01 0.00018 1.3E-03 -0.00006 5.5E-01 0.00002 7.9E-01 Eubacterium_biforme UniRef90_B7CEA1 Cluster: Uncharacterized protein 0.20 -0.00009 8.7E-02 2.7E-01 -0.00004 6.4E-01 0.00010 6.7E-02 0.00009 3.9E-01 -0.00003 6.6E-01 Eubacterium_biforme UniRef90_A7AZQ0 Cluster: Uncharacterized protein 0.24 -0.00011 1.2E-01 3.5E-01 -0.00032 9.8E-03 0.00002 8.1E-01 0.00008 5.5E-01 -0.00009 2.8E-01 Eubacterium_biforme UniRef90_B7C978 Cluster: Uncharacterized protein 0.24 0.00001 8.9E-01 9.6E-01 -0.00004 6.2E-01 0.00010 2.2E-02 0.00005 5.6E-01 -0.00001 8.5E-01 Eubacterium_hallii UniRef90_C0EV01 Cluster: OrfB_Zn_ribbon domain-containing protein (Fragment) 0.56 0.00029 4.6E-04 2.1E-02 -0.00004 7.0E-01 0.00005 5.5E-01 0.00022 1.0E-01 0.00008 4.4E-01 Eubacterium_hallii UniRef90_C0EU54 Cluster: Transposase, IS605 family (Fragment) 0.90 0.00019 8.6E-04 2.3E-02 0.00008 3.5E-01 0.00001 8.9E-01 0.00009 3.9E-01 0.00004 6.0E-01 Eubacterium_hallii UniRef90_C0ETH6 Cluster: Transposase (Fragment) 0.91 0.00015 7.4E-04 2.3E-02 0.00004 5.3E-01 -0.00001 7.6E-01 0.00009 2.2E-01 0.00004 4.3E-01 Eubacterium_hallii UniRef90_C0F091 Cluster: HTH_OrfB_IS605 domain-containing protein (Fragment) 0.80 0.00019 7.2E-04 2.5E-02 0.00001 8.5E-01 -0.00004 4.4E-01 0.00009 3.7E-01 0.00007 2.6E-01 Eubacterium_hallii UniRef90_C0F0E1 Cluster: HTH_OrfB_IS605 domain-containing protein (Fragment) 0.84 0.00023 3.7E-04 2.8E-02 0.00004 6.9E-01 -0.00001 9.1E-01 0.00017 1.2E-01 0.00008 3.0E-01 Eubacterium_hallii UniRef90_R6G4R8 Cluster: Putative transposase DNA-binding domain protein 0.81 0.00015 1.8E-03 4.0E-02 0.00002 7.5E-01 -0.00002 6.8E-01 0.00011 1.8E-01 -0.00001 7.9E-01 Eubacterium_hallii UniRef90_C0F0P0 Cluster: IS3 family transposase 0.82 0.00031 3.6E-03 4.6E-02 0.00004 8.2E-01 -0.00010 3.7E-01 0.00008 6.7E-01 0.00002 8.5E-01 Eubacterium_hallii UniRef90_C0EZW2 Cluster: Y1_Tnp domain-containing protein 0.77 0.00015 5.5E-03 5.0E-02 0.00009 2.0E-01 0.00000 9.7E-01 0.00012 1.8E-01 0.00007 2.6E-01 Eubacterium_hallii UniRef90_C0EVW9 Cluster: HTH_OrfB_IS605 domain-containing protein (Fragment) 0.38 0.00019 1.2E-02 7.7E-02 0.00015 1.1E-01 0.00000 9.9E-01 0.00004 7.2E-01 -0.00004 6.7E-01 Eubacterium_hallii UniRef90_R6GY12 Cluster: Transposase and inactivated derivatives 0.81 0.00017 3.2E-02 1.6E-01 0.00003 8.2E-01 -0.00009 2.6E-01 0.00009 5.1E-01 0.00003 7.6E-01 Eubacterium_hallii UniRef90_C0EWA5 Cluster: IS200/IS605 family transposase 0.87 0.00007 8.3E-02 2.7E-01 0.00008 2.0E-01 0.00000 9.6E-01 -0.00004 6.4E-01 0.00000 9.9E-01 Eubacterium_hallii UniRef90_C6JCB6 Cluster: Thioredoxin 0.90 0.00007 1.7E-01 4.2E-01 0.00005 4.8E-01 0.00002 7.3E-01 0.00003 7.1E-01 0.00007 2.0E-01 Eubacterium_hallii UniRef90_C0EVN8 Cluster: HTH cro/C1-type domain-containing protein 0.77 0.00007 1.7E-01 4.2E-01 0.00007 3.1E-01 -0.00001 8.9E-01 0.00008 3.9E-01 0.00009 1.5E-01 Eubacterium_hallii UniRef90_C0EVZ2 Cluster: Response regulatory domain-containing protein 0.91 0.00006 2.0E-01 4.7E-01 0.00009 1.6E-01 0.00002 6.5E-01 -0.00002 7.6E-01 0.00002 7.7E-01 Eubacterium_hallii UniRef90_D4MWC5 Cluster: DNA-binding response regulator 0.92 0.00004 2.9E-01 5.9E-01 0.00002 7.5E-01 -0.00001 8.4E-01 -0.00007 3.0E-01 0.00000 9.8E-01 Eubacterium_hallii UniRef90_C4ZHG9 Cluster: Rhodanese domain-containing protein 0.92 0.00004 3.0E-01 5.9E-01 0.00000 9.7E-01 -0.00001 7.5E-01 0.00004 5.2E-01 0.00005 2.6E-01 Eubacterium_hallii UniRef90_C4ZFJ8 Cluster: Transcriptional regulator, y4mF family 0.73 0.00006 3.1E-01 6.0E-01 0.00002 7.9E-01 0.00000 9.4E-01 -0.00002 8.0E-01 -0.00003 6.4E-01 Eubacterium_hallii UniRef90_D4JN77 Cluster: HTH cro/C1-type domain-containing protein 0.92 -0.00004 3.7E-01 6.9E-01 -0.00002 7.9E-01 -0.00003 4.5E-01 -0.00006 4.0E-01 0.00000 9.9E-01 Eubacterium_hallii UniRef90_R7EJY9 Cluster: Conjugal transfer protein 0.84 -0.00005 3.8E-01 7.0E-01 0.00010 2.8E-01 -0.00004 5.6E-01 -0.00009 3.9E-01 -0.00004 5.9E-01 Eubacterium_hallii UniRef90_D4MZR3 Cluster: OrfB_Zn_ribbon domain-containing protein 0.91 0.00004 4.2E-01 7.4E-01 0.00007 3.6E-01 -0.00003 4.8E-01 -0.00003 6.8E-01 0.00000 9.9E-01 41

Supplementary Data 3a Red meat Red meat Choline intake- Choline UniRef90 Family Detection Plasma TMAO Species Cluster Name intake-FFQ intake-7DDR FFQ intake-7DDR member ID Rate Effect P FDR Effect P Effect P Effect P Effect P Eubacterium_hallii UniRef90_T5LJS0 Cluster: DNA-binding protein 0.74 -0.00004 4.5E-01 7.6E-01 -0.00013 1.3E-01 -0.00002 7.7E-01 -0.00021 4.8E-02 -0.00004 5.1E-01 Eubacterium_hallii UniRef90_C4Z770 Cluster: Flavodoxin family protein 0.92 -0.00004 5.0E-01 8.2E-01 0.00001 9.4E-01 -0.00005 3.3E-01 -0.00006 5.3E-01 -0.00004 5.6E-01 Eubacterium_hallii UniRef90_D4LZV0 Cluster: Single-stranded DNA-binding protein 0.83 -0.00003 5.0E-01 8.2E-01 -0.00007 3.7E-01 -0.00007 1.6E-01 -0.00018 3.9E-02 -0.00002 6.7E-01 Eubacterium_hallii UniRef90_C4ZFJ6 Cluster: DNA polymerase IV 0.91 -0.00003 5.1E-01 8.2E-01 -0.00008 2.3E-01 -0.00004 3.1E-01 -0.00013 1.0E-01 -0.00004 4.3E-01 Eubacterium_hallii UniRef90_C4ZE34 Cluster: DUF4366 domain-containing protein 0.91 0.00003 5.2E-01 8.2E-01 0.00000 9.7E-01 -0.00002 5.5E-01 -0.00005 5.2E-01 -0.00003 5.6E-01 Eubacterium_hallii UniRef90_C4ZFF7 Cluster: Nucleotidyl transferase AbiEii/AbiGii toxin family protein 0.87 -0.00003 5.1E-01 8.2E-01 0.00000 9.5E-01 0.00000 9.6E-01 -0.00002 8.3E-01 0.00000 9.9E-01 Eubacterium_hallii UniRef90_C4Z763 Cluster: GTP pyrophosphokinase ywaC 0.92 0.00002 6.0E-01 8.6E-01 0.00005 3.4E-01 -0.00004 2.2E-01 -0.00002 7.9E-01 0.00001 7.7E-01 Eubacterium_hallii UniRef90_C4ZFF0 Cluster: HTH_17 domain-containing protein 0.87 0.00003 6.2E-01 8.7E-01 -0.00002 8.3E-01 0.00002 7.7E-01 -0.00004 6.4E-01 -0.00004 4.9E-01 Eubacterium_hallii UniRef90_D4JJU3 Cluster: LexA repressor 0.88 -0.00002 6.6E-01 8.7E-01 -0.00007 2.9E-01 0.00000 9.3E-01 -0.00009 2.0E-01 -0.00003 5.6E-01 Eubacterium_hallii UniRef90_C0EXI9 Cluster: VanY domain-containing protein 0.50 0.00003 6.5E-01 8.7E-01 -0.00001 9.5E-01 -0.00008 2.6E-01 0.00009 4.3E-01 -0.00002 7.8E-01 Eubacterium_hallii UniRef90_C0EVN9 Cluster: Zn_ribbon_2 domain-containing protein 0.90 -0.00002 6.2E-01 8.7E-01 0.00002 6.7E-01 0.00002 5.8E-01 0.00001 8.4E-01 0.00002 6.2E-01 Eubacterium_hallii UniRef90_C4ZFG0 Cluster: Sensor protein kinase walK 0.91 0.00002 6.4E-01 8.8E-01 0.00009 1.7E-01 0.00002 7.4E-01 0.00001 9.3E-01 0.00007 1.8E-01 Eubacterium_hallii UniRef90_D4LKY8 Cluster: ABC transporter domain-containing protein 0.91 0.00001 7.4E-01 8.9E-01 0.00011 6.8E-02 0.00003 5.4E-01 -0.00001 9.4E-01 0.00003 5.3E-01 Eubacterium_hallii UniRef90_A7B829 Cluster: ALP_N domain-containing protein 0.91 0.00001 7.3E-01 8.9E-01 -0.00002 7.5E-01 -0.00002 5.7E-01 -0.00001 9.1E-01 -0.00001 8.0E-01 Eubacterium_hallii UniRef90_D4LFS2 Cluster: RNA polymerase sigma factor, sigma-70 family 0.89 0.00001 7.7E-01 9.0E-01 -0.00013 6.0E-02 -0.00005 3.0E-01 -0.00015 6.4E-02 0.00000 9.6E-01 Eubacterium_hallii UniRef90_C4ZE67 Cluster: Primosomal protein DnaI 0.88 -0.00001 8.7E-01 9.5E-01 -0.00003 6.1E-01 -0.00005 2.2E-01 -0.00018 1.6E-02 -0.00003 5.3E-01 Eubacterium_hallii UniRef90_D4L240 Cluster: CDP-diacylglycerol--glycerol-3-phosphate 3-phosphatidyltransferase 0.92 -0.00001 8.9E-01 9.6E-01 -0.00001 9.1E-01 -0.00002 6.0E-01 -0.00003 6.5E-01 0.00001 7.5E-01 Eubacterium_hallii UniRef90_C4ZFD9 Cluster: DNA-binding response regulator 0.92 0.00001 8.9E-01 9.6E-01 0.00000 9.5E-01 -0.00002 5.5E-01 -0.00008 2.1E-01 0.00003 5.8E-01 Eubacterium_hallii UniRef90_C4ZFJ2 Cluster: Phage transcriptional regulator, ArpU family 0.91 0.00000 9.1E-01 9.7E-01 -0.00010 1.3E-01 -0.00005 2.8E-01 -0.00017 2.5E-02 -0.00005 3.0E-01 Eubacterium_hallii UniRef90_C4ZFF1 Cluster: Relaxasome subunit MobC 0.91 0.00000 9.3E-01 9.8E-01 -0.00004 5.1E-01 -0.00001 8.4E-01 -0.00006 4.2E-01 -0.00005 3.5E-01 Eubacterium_hallii UniRef90_D4LLG0 Cluster: Choloylglycine hydrolase 0.92 0.00000 9.3E-01 9.8E-01 0.00007 1.9E-01 -0.00006 1.4E-01 -0.00005 4.0E-01 0.00001 7.6E-01 Eubacterium_hallii UniRef90_C4ZFF8 Cluster: Transcriptional regulatory protein walR 0.91 0.00000 9.6E-01 9.8E-01 0.00006 3.3E-01 0.00000 9.2E-01 -0.00003 7.4E-01 0.00003 5.5E-01 Eubacterium_hallii UniRef90_C4ZFI5 Cluster: mRNA interferase 0.86 0.00000 9.5E-01 9.9E-01 -0.00013 7.4E-02 -0.00007 1.2E-01 -0.00016 6.6E-02 -0.00008 1.4E-01 Eubacterium_hallii UniRef90_D4LKZ0 Cluster: VanZ domain-containing protein 0.90 0.00000 9.6E-01 9.9E-01 0.00008 2.4E-01 0.00003 4.3E-01 -0.00003 6.6E-01 0.00004 4.1E-01 Eubacterium_hallii UniRef90_C0EVY7 Cluster: HATPase_c_4 domain-containing protein 0.91 0.00000 9.9E-01 1.0E+00 0.00007 2.7E-01 -0.00005 2.6E-01 0.00004 6.6E-01 0.00001 7.9E-01 Eubacterium_hallii UniRef90_C4ZFK0 Cluster: Plasmid mobilization relaxosome protein MobC 0.79 0.00000 9.9E-01 1.0E+00 0.00009 2.2E-01 -0.00006 1.9E-01 0.00000 9.9E-01 0.00003 6.1E-01 Eubacterium_hallii UniRef90_C0EYX0 Cluster: Uncharacterized protein (Fragment) 0.61 0.00025 5.9E-04 2.2E-02 0.00003 7.4E-01 0.00002 8.1E-01 0.00013 3.0E-01 0.00006 4.6E-01 Eubacterium_hallii UniRef90_C0F0G9 Cluster: Uncharacterized protein 0.53 0.00021 3.8E-04 2.4E-02 -0.00002 8.0E-01 -0.00001 8.6E-01 0.00011 2.4E-01 0.00012 9.9E-02 Eubacterium_hallii UniRef90_C0ETY7 Cluster: Uncharacterized protein 0.55 0.00017 2.2E-03 3.8E-02 -0.00001 9.0E-01 -0.00001 8.8E-01 0.00003 7.3E-01 0.00008 2.2E-01 Eubacterium_hallii unknown Unknown gene identity 0.92 0.00088 2.2E-03 3.9E-02 0.00013 7.5E-01 -0.00021 4.7E-01 0.00038 4.5E-01 0.00018 6.1E-01 Eubacterium_hallii UniRef90_C0EZW3 Cluster: Uncharacterized protein 0.52 0.00019 2.5E-03 4.0E-02 -0.00002 7.8E-01 0.00001 8.2E-01 0.00007 5.1E-01 0.00010 1.9E-01 Eubacterium_hallii UniRef90_C0ERW4 Cluster: Uncharacterized protein 0.65 0.00019 4.1E-03 4.5E-02 0.00002 8.1E-01 -0.00004 5.6E-01 0.00008 5.0E-01 0.00012 1.5E-01 Eubacterium_hallii UniRef90_C0ET14 Cluster: Uncharacterized protein 0.75 0.00021 3.4E-03 4.5E-02 0.00000 9.7E-01 0.00003 7.2E-01 0.00013 2.9E-01 0.00013 1.3E-01 Eubacterium_hallii UniRef90_C0EYS0 Cluster: Uncharacterized protein 0.88 0.00019 4.0E-03 4.6E-02 -0.00001 9.0E-01 -0.00002 8.2E-01 0.00011 3.0E-01 0.00008 3.0E-01 Eubacterium_hallii UniRef90_C0F0S2 Cluster: Uncharacterized protein 0.69 0.00018 3.2E-03 4.6E-02 0.00000 9.8E-01 -0.00005 4.8E-01 0.00010 3.6E-01 0.00005 4.9E-01 Eubacterium_hallii UniRef90_C0EXA5 Cluster: Uncharacterized protein (Fragment) 0.38 0.00016 4.9E-03 4.8E-02 -0.00004 6.4E-01 -0.00004 5.5E-01 0.00006 5.4E-01 0.00001 8.6E-01 Eubacterium_hallii UniRef90_C0EUY1 Cluster: Uncharacterized protein 0.71 0.00022 5.0E-03 4.8E-02 -0.00001 9.0E-01 -0.00002 7.8E-01 0.00013 3.4E-01 -0.00002 8.1E-01 Eubacterium_hallii UniRef90_C0EWK2 Cluster: Uncharacterized protein 0.78 0.00014 6.1E-03 5.3E-02 0.00001 9.0E-01 -0.00002 7.2E-01 0.00012 1.7E-01 0.00005 4.3E-01 Eubacterium_hallii UniRef90_C0ETX8 Cluster: Uncharacterized protein 0.72 0.00013 7.3E-03 5.6E-02 0.00002 7.7E-01 -0.00004 4.1E-01 0.00006 4.8E-01 0.00000 9.7E-01 Eubacterium_hallii UniRef90_C0EZ12 Cluster: Uncharacterized protein 0.81 0.00021 2.2E-02 1.3E-01 0.00004 7.9E-01 -0.00008 3.7E-01 -0.00003 8.6E-01 -0.00005 6.5E-01 Eubacterium_hallii UniRef90_C0EUT4 Cluster: Uncharacterized protein 0.71 0.00014 2.7E-02 1.4E-01 -0.00001 9.4E-01 -0.00008 2.2E-01 0.00002 8.4E-01 0.00001 8.9E-01 Eubacterium_hallii UniRef90_C0EZ83 Cluster: Uncharacterized protein 0.74 0.00011 3.3E-02 1.6E-01 -0.00001 8.4E-01 -0.00009 8.8E-02 -0.00001 8.7E-01 0.00003 6.5E-01 Eubacterium_hallii UniRef90_C0ETY5 Cluster: Uncharacterized protein 0.44 0.00014 4.2E-02 1.8E-01 -0.00005 5.4E-01 -0.00009 2.0E-01 -0.00001 9.3E-01 -0.00004 6.3E-01 Eubacterium_hallii UniRef90_C0ESA6 Cluster: Uncharacterized protein 0.62 0.00018 4.6E-02 1.9E-01 0.00006 6.5E-01 -0.00004 6.5E-01 0.00002 9.0E-01 -0.00008 4.4E-01 Eubacterium_hallii UniRef90_C0EVX8 Cluster: Uncharacterized protein 0.85 0.00009 5.8E-02 2.2E-01 0.00004 5.6E-01 -0.00002 7.2E-01 -0.00002 8.1E-01 0.00008 1.6E-01 Eubacterium_hallii UniRef90_C0ETE4 Cluster: Uncharacterized protein 0.53 0.00011 8.0E-02 2.7E-01 -0.00006 4.8E-01 -0.00003 6.2E-01 0.00018 9.0E-02 0.00006 4.5E-01 Eubacterium_hallii UniRef90_C0EZZ4 Cluster: Uncharacterized protein 0.81 0.00007 1.4E-01 3.8E-01 0.00008 2.1E-01 -0.00003 5.0E-01 0.00008 2.9E-01 0.00000 9.8E-01 Eubacterium_hallii UniRef90_C0EVA4 Cluster: Uncharacterized protein 0.88 0.00007 1.9E-01 4.4E-01 0.00003 6.3E-01 -0.00004 4.6E-01 0.00009 3.1E-01 0.00006 3.1E-01 Eubacterium_hallii UniRef90_C0EVZ3 Cluster: Uncharacterized protein 0.88 0.00005 2.6E-01 5.6E-01 0.00012 9.0E-02 0.00004 3.9E-01 0.00004 6.1E-01 0.00006 3.1E-01 Eubacterium_hallii UniRef90_C4ZFJ4 Cluster: Uncharacterized protein 0.80 -0.00006 2.8E-01 5.8E-01 -0.00017 4.2E-02 -0.00003 5.5E-01 -0.00014 1.7E-01 -0.00001 8.4E-01 Eubacterium_hallii UniRef90_C4ZE30 Cluster: Uncharacterized protein 0.69 0.00006 3.6E-01 6.8E-01 0.00005 6.1E-01 -0.00001 9.3E-01 -0.00008 4.6E-01 -0.00007 4.0E-01 Eubacterium_hallii UniRef90_C4ZE70 Cluster: Uncharacterized protein 0.80 -0.00004 3.6E-01 6.8E-01 -0.00011 1.6E-01 -0.00007 1.7E-01 -0.00020 2.7E-02 -0.00009 1.3E-01 Eubacterium_hallii UniRef90_C4ZFF4 Cluster: Uncharacterized protein 0.92 -0.00004 4.0E-01 7.2E-01 -0.00001 8.5E-01 -0.00002 6.8E-01 -0.00003 7.1E-01 -0.00007 2.1E-01 Eubacterium_hallii UniRef90_G2T5D0 Cluster: Uncharacterized protein 0.91 0.00003 4.3E-01 7.4E-01 0.00000 9.4E-01 -0.00001 7.9E-01 -0.00002 7.5E-01 0.00001 8.3E-01 Eubacterium_hallii UniRef90_C0EUU4 Cluster: Uncharacterized protein 0.79 -0.00003 5.4E-01 8.3E-01 -0.00002 8.2E-01 -0.00004 4.5E-01 -0.00002 8.3E-01 0.00005 4.2E-01 Eubacterium_hallii UniRef90_G2SY36 Cluster: Uncharacterized protein 0.91 -0.00003 5.9E-01 8.6E-01 -0.00004 5.6E-01 -0.00001 7.8E-01 -0.00009 3.0E-01 -0.00001 8.0E-01 Eubacterium_hallii UniRef90_R5FY56 Cluster: Uncharacterized protein 0.84 0.00002 6.9E-01 8.7E-01 -0.00004 6.2E-01 -0.00007 2.3E-01 0.00004 6.6E-01 0.00003 6.1E-01 Eubacterium_hallii UniRef90_G2T4G5 Cluster: Uncharacterized protein 0.83 -0.00003 6.9E-01 8.7E-01 0.00011 2.8E-01 -0.00012 1.2E-01 -0.00012 3.5E-01 -0.00008 3.7E-01 Eubacterium_hallii UniRef90_B0P4L9 Cluster: Uncharacterized protein 0.84 -0.00002 6.2E-01 8.7E-01 0.00009 2.1E-01 0.00000 9.9E-01 0.00003 7.5E-01 -0.00001 8.0E-01 Eubacterium_hallii UniRef90_B7C9H1 Cluster: Uncharacterized protein 0.91 0.00002 6.8E-01 8.7E-01 0.00008 2.2E-01 -0.00002 7.0E-01 -0.00007 3.6E-01 0.00004 4.8E-01 Eubacterium_hallii UniRef90_C4ZFF6 Cluster: Uncharacterized protein 0.89 -0.00002 6.4E-01 8.7E-01 0.00003 6.5E-01 -0.00002 7.0E-01 0.00001 9.2E-01 -0.00004 4.5E-01 Eubacterium_hallii UniRef90_C6JCC0 Cluster: Uncharacterized protein 0.91 0.00001 7.3E-01 8.9E-01 0.00004 4.2E-01 -0.00001 7.6E-01 -0.00001 8.8E-01 0.00002 6.3E-01 Eubacterium_hallii UniRef90_C0EVY8 Cluster: Uncharacterized protein 0.67 0.00002 7.4E-01 8.9E-01 0.00017 9.3E-02 -0.00010 1.8E-01 -0.00006 6.1E-01 0.00000 9.8E-01 Eubacterium_hallii UniRef90_C0EYT7 Cluster: Uncharacterized protein 0.86 -0.00002 7.3E-01 8.9E-01 0.00000 9.4E-01 -0.00005 2.8E-01 -0.00005 5.2E-01 0.00003 5.8E-01 42

Supplementary Data 3a Red meat Red meat Choline intake- Choline UniRef90 Family Detection Plasma TMAO Species Cluster Name intake-FFQ intake-7DDR FFQ intake-7DDR member ID Rate Effect P FDR Effect P Effect P Effect P Effect P Eubacterium_hallii UniRef90_C0EYU8 Cluster: Uncharacterized protein 0.82 -0.00001 7.5E-01 8.9E-01 0.00006 3.7E-01 0.00004 4.1E-01 0.00007 3.7E-01 0.00012 3.1E-02 Eubacterium_hallii UniRef90_C4ZFJ1 Cluster: Uncharacterized protein 0.90 0.00001 8.1E-01 9.1E-01 0.00001 9.0E-01 -0.00003 5.1E-01 -0.00012 1.4E-01 -0.00001 8.2E-01 Eubacterium_hallii UniRef90_C4ZFG2 Cluster: Uncharacterized protein 0.92 -0.00001 8.1E-01 9.2E-01 0.00007 2.7E-01 0.00001 7.5E-01 0.00004 5.9E-01 0.00000 9.8E-01 Eubacterium_hallii UniRef90_C4ZE39 Cluster: Uncharacterized protein 0.91 -0.00001 8.1E-01 9.2E-01 0.00003 6.4E-01 -0.00001 7.6E-01 -0.00010 2.1E-01 -0.00003 6.4E-01 Eubacterium_hallii UniRef90_C0ESV0 Cluster: Uncharacterized protein 0.88 -0.00002 8.1E-01 9.2E-01 -0.00013 3.5E-01 -0.00015 1.0E-01 -0.00023 1.4E-01 -0.00006 5.5E-01 Eubacterium_hallii UniRef90_C0EYV3 Cluster: Uncharacterized protein 0.87 -0.00001 7.9E-01 9.2E-01 0.00004 5.6E-01 -0.00003 4.4E-01 0.00007 3.3E-01 0.00003 6.2E-01 Eubacterium_hallii UniRef90_C0ESR9 Cluster: Uncharacterized protein 0.59 -0.00001 8.0E-01 9.2E-01 0.00001 8.3E-01 -0.00005 2.1E-01 -0.00010 1.9E-01 -0.00010 4.2E-02 Eubacterium_hallii UniRef90_C7GG49 Cluster: Uncharacterized protein 0.72 0.00001 8.6E-01 9.5E-01 -0.00006 4.6E-01 -0.00014 9.1E-03 -0.00009 3.1E-01 -0.00004 5.2E-01 Eubacterium_hallii UniRef90_R5J281 Cluster: Uncharacterized protein 0.87 0.00001 8.6E-01 9.5E-01 0.00001 9.1E-01 -0.00001 8.0E-01 0.00004 6.8E-01 0.00001 8.7E-01 Eubacterium_hallii UniRef90_C0ESQ1 Cluster: Uncharacterized protein 0.86 0.00001 9.0E-01 9.6E-01 0.00007 3.6E-01 -0.00001 8.2E-01 -0.00009 3.2E-01 -0.00003 6.3E-01 Eubacterium_hallii UniRef90_C0ESN9 Cluster: Uncharacterized protein 0.86 0.00001 9.1E-01 9.7E-01 -0.00005 5.2E-01 -0.00004 3.8E-01 -0.00012 2.0E-01 -0.00003 5.6E-01 Eubacterium_hallii UniRef90_C4ZFG4 Cluster: Uncharacterized protein 0.91 0.00000 9.5E-01 9.9E-01 -0.00002 8.2E-01 -0.00001 8.6E-01 -0.00003 8.0E-01 0.00000 9.8E-01 Eubacterium_hallii UniRef90_G2T5K3 Cluster: Uncharacterized protein 0.92 0.00000 9.6E-01 9.9E-01 0.00000 1.0E+00 -0.00003 4.0E-01 -0.00004 5.8E-01 0.00001 8.5E-01 Eubacterium_hallii UniRef90_C4ZE66 Cluster: Uncharacterized protein 0.88 0.00000 9.8E-01 1.0E+00 0.00005 4.1E-01 0.00000 9.4E-01 -0.00010 2.1E-01 -0.00005 3.2E-01 Eubacterium_hallii UniRef90_C0EWA3 Cluster: Uncharacterized protein 0.83 0.00000 1.0E+00 1.0E+00 0.00015 4.8E-02 0.00005 3.5E-01 0.00002 8.6E-01 0.00006 3.7E-01 Eubacterium_hallii UniRef90_C4ZE38 Cluster: Uncharacterized protein 0.89 0.00000 9.9E-01 1.0E+00 0.00001 9.0E-01 -0.00003 5.2E-01 -0.00009 3.6E-01 -0.00003 5.8E-01 Roseburia_hominis UniRef90_R6CT57 Cluster: 30S ribosomal protein S14 type Z 0.69 0.00015 2.0E-03 3.7E-02 0.00007 3.5E-01 -0.00001 8.2E-01 -0.00002 8.1E-01 0.00003 5.8E-01 Roseburia_hominis UniRef90_G2T376 Cluster: MobC domain-containing protein 0.83 0.00013 1.9E-03 4.0E-02 -0.00002 7.9E-01 0.00000 9.7E-01 0.00000 1.0E+00 -0.00006 2.0E-01 Roseburia_hominis UniRef90_G2T382 Cluster: DUF4366 domain-containing protein 0.86 0.00011 4.1E-03 4.4E-02 -0.00001 9.2E-01 -0.00003 5.1E-01 0.00008 2.6E-01 -0.00001 7.8E-01 Roseburia_hominis UniRef90_G2T375 Cluster: Relaxase/mobilization nuclease family protein 0.86 0.00011 5.2E-03 4.8E-02 0.00001 8.5E-01 0.00000 1.0E+00 0.00007 2.9E-01 0.00001 7.6E-01 Roseburia_hominis UniRef90_G2T384 Cluster: D-gamma-glutamyl-meso-diaminopimelic acid endopeptidase CwlS 0.86 0.00011 6.8E-03 5.4E-02 -0.00002 7.2E-01 -0.00003 4.0E-01 0.00004 6.0E-01 -0.00001 8.2E-01 Roseburia_hominis UniRef90_G2T383 Cluster: Isocitrate/isopropylmalate dehydrogenase 0.80 0.00012 9.7E-03 6.8E-02 -0.00001 9.3E-01 -0.00001 8.3E-01 0.00005 5.7E-01 -0.00004 5.1E-01 Roseburia_hominis UniRef90_G2T387 Cluster: DNA methyltransferase 0.84 0.00011 1.1E-02 7.5E-02 0.00001 9.2E-01 0.00001 8.0E-01 0.00005 5.6E-01 0.00000 9.5E-01 Roseburia_hominis UniRef90_G2T380 Cluster: Cys_rich_VLP domain-containing protein 0.86 0.00014 1.3E-02 8.4E-02 0.00002 7.7E-01 -0.00005 3.5E-01 0.00005 5.9E-01 -0.00001 9.0E-01 Roseburia_hominis UniRef90_D4K3K8 Cluster: Methyltransferase 0.86 0.00011 1.6E-02 9.8E-02 0.00000 9.8E-01 -0.00004 4.4E-01 0.00005 5.5E-01 -0.00001 8.4E-01 Roseburia_hominis UniRef90_G2SYQ7 Cluster: Macro domain-containing protein 0.83 0.00015 2.5E-02 1.3E-01 -0.00014 1.4E-01 -0.00015 3.2E-02 0.00006 6.1E-01 0.00002 8.3E-01 Roseburia_hominis UniRef90_G2SYX8 Cluster: Methyl-accepting transducer domain-containing protein 0.43 0.00015 2.9E-02 1.5E-01 -0.00009 3.7E-01 -0.00001 8.5E-01 0.00005 6.5E-01 -0.00012 1.3E-01 Roseburia_hominis UniRef90_C4Z753 Cluster: Choloylglycine hydrolase 0.87 0.00009 3.5E-02 1.7E-01 0.00009 1.7E-01 0.00005 3.0E-01 0.00005 5.3E-01 0.00002 6.9E-01 Roseburia_hominis UniRef90_G2T3A1 Cluster: TraG/TraD family protein 0.86 0.00009 3.8E-02 1.7E-01 -0.00001 9.3E-01 0.00001 8.5E-01 0.00003 7.5E-01 0.00003 5.7E-01 Roseburia_hominis UniRef90_C4ZBU2 Cluster: 50S ribosomal protein L36 0.57 0.00020 5.4E-02 2.2E-01 0.00013 3.6E-01 -0.00010 3.3E-01 -0.00009 5.9E-01 -0.00016 2.0E-01 Roseburia_hominis UniRef90_D4L1Y4 Cluster: HTH cro/C1-type domain-containing protein 0.87 0.00011 5.7E-02 2.2E-01 0.00018 4.0E-02 0.00000 9.7E-01 0.00003 7.6E-01 -0.00001 8.7E-01 Roseburia_hominis UniRef90_D4KMP8 Cluster: RLX-like protein 0.87 0.00008 5.8E-02 2.2E-01 0.00009 1.4E-01 0.00000 9.9E-01 -0.00001 9.2E-01 -0.00003 5.1E-01 Roseburia_hominis UniRef90_D4L1Y7 Cluster: Histidine kinase domain-containing protein 0.87 0.00007 5.9E-02 2.3E-01 0.00015 6.1E-03 -0.00001 7.8E-01 0.00004 5.4E-01 0.00003 5.1E-01 Roseburia_hominis UniRef90_G2T3T3 Cluster: TRAG family protein 0.86 0.00007 6.0E-02 2.3E-01 0.00001 8.3E-01 -0.00002 5.6E-01 0.00003 6.5E-01 0.00002 6.9E-01 Roseburia_hominis UniRef90_G2T378 Cluster: DarA_C domain-containing protein 0.86 0.00008 6.4E-02 2.3E-01 -0.00001 9.3E-01 -0.00004 3.9E-01 0.00000 9.5E-01 0.00001 8.2E-01 Roseburia_hominis UniRef90_C4Z640 Cluster: HAMP domain-containing protein 0.87 0.00009 7.3E-02 2.5E-01 0.00002 8.2E-01 -0.00003 5.9E-01 -0.00001 8.8E-01 -0.00003 5.6E-01 Roseburia_hominis UniRef90_G2T4T7 Cluster: Mutator family transposase 0.86 0.00013 7.6E-02 2.5E-01 0.00001 9.5E-01 0.00001 8.9E-01 0.00013 3.2E-01 0.00006 5.0E-01 Roseburia_hominis UniRef90_C4Z796 Cluster: Peroxide-responsive repressor perR 0.86 0.00007 8.2E-02 2.7E-01 0.00003 6.6E-01 -0.00004 3.4E-01 -0.00003 6.9E-01 -0.00001 8.6E-01 Roseburia_hominis UniRef90_G2T2M9 Cluster: HTH_17 domain-containing protein 0.86 0.00011 8.2E-02 2.7E-01 0.00024 7.8E-03 0.00008 2.0E-01 0.00013 2.5E-01 -0.00003 6.4E-01 Roseburia_hominis UniRef90_D4L240 Cluster: CDP-diacylglycerol--glycerol-3-phosphate 3-phosphatidyltransferase 0.87 0.00007 8.6E-02 2.8E-01 0.00004 5.1E-01 -0.00001 8.7E-01 -0.00003 7.1E-01 -0.00002 6.7E-01 Roseburia_hominis UniRef90_D4KMP9 Cluster: DUF3991 domain-containing protein 0.87 0.00008 9.1E-02 2.8E-01 0.00011 1.1E-01 0.00000 9.4E-01 0.00006 4.5E-01 -0.00004 4.9E-01 Roseburia_hominis UniRef90_C9YME3 Cluster: Two-component response regulator 0.87 0.00007 9.6E-02 2.9E-01 0.00012 3.9E-02 -0.00002 7.0E-01 0.00002 7.8E-01 -0.00002 6.4E-01 Roseburia_hominis UniRef90_G2SZW3 Cluster: Glutathione synthase 0.86 0.00008 1.1E-01 3.3E-01 0.00012 1.1E-01 -0.00001 8.9E-01 0.00001 9.0E-01 -0.00006 3.3E-01 Roseburia_hominis UniRef90_G2T4T8 Cluster: Histidine kinase 0.83 0.00007 1.3E-01 3.6E-01 0.00017 2.1E-02 0.00000 9.6E-01 0.00031 2.1E-04 -0.00001 8.7E-01 Roseburia_hominis UniRef90_G2SZT5 Cluster: ParB-like partition protein 0.87 0.00006 1.3E-01 3.6E-01 0.00004 5.2E-01 -0.00003 4.3E-01 0.00000 9.6E-01 -0.00006 1.8E-01 Roseburia_hominis UniRef90_G2T3T7 Cluster: Probable chromosome-partitioning protein parB 0.87 0.00006 1.3E-01 3.6E-01 -0.00001 8.7E-01 -0.00003 4.5E-01 0.00002 8.0E-01 0.00004 4.3E-01 Roseburia_hominis UniRef90_D4JEE9 Cluster: TraG/TraD family protein 0.87 0.00007 1.4E-01 3.8E-01 0.00008 2.7E-01 -0.00003 4.8E-01 0.00004 6.6E-01 -0.00009 9.6E-02 Roseburia_hominis UniRef90_D4L1Y8 Cluster: Sigma70_r4_2 domain-containing protein 0.87 0.00008 1.7E-01 4.2E-01 0.00012 2.0E-01 -0.00007 2.8E-01 0.00008 4.8E-01 0.00002 7.5E-01 Roseburia_hominis UniRef90_C4Z761 Cluster: Citrate synthase 0.87 0.00006 1.7E-01 4.2E-01 0.00001 8.1E-01 -0.00001 8.3E-01 -0.00009 2.5E-01 -0.00005 2.7E-01 Roseburia_hominis UniRef90_A5ZNT5 Cluster: Resolvase, N-terminal domain protein 0.87 0.00006 1.9E-01 4.6E-01 0.00013 5.3E-02 -0.00001 8.5E-01 0.00007 4.1E-01 -0.00002 6.7E-01 Roseburia_hominis UniRef90_G2T4V4 Cluster: HTH cro/C1-type domain-containing protein 0.62 -0.00007 2.0E-01 4.6E-01 0.00012 1.4E-01 0.00000 9.4E-01 0.00016 7.9E-02 0.00013 3.0E-02 Roseburia_hominis UniRef90_G2T0J2 Cluster: DNA-binding protein 0.72 0.00006 2.2E-01 4.9E-01 0.00008 2.7E-01 -0.00005 3.3E-01 -0.00002 7.8E-01 0.00006 3.3E-01 Roseburia_hominis UniRef90_D4LS34 Cluster: ATP-binding cassette domain-containing protein 0.83 0.00005 2.4E-01 5.4E-01 0.00014 3.8E-02 0.00002 5.7E-01 0.00028 3.1E-04 0.00000 9.4E-01 Roseburia_hominis UniRef90_G2T2N2 Cluster: DNA strand transferase 0.87 0.00006 2.4E-01 5.4E-01 0.00015 4.7E-02 0.00002 6.4E-01 0.00015 8.6E-02 -0.00003 6.1E-01 Roseburia_hominis UniRef90_C4Z791 Cluster: Hemerythrin 0.85 0.00007 2.5E-01 5.5E-01 0.00001 9.0E-01 -0.00006 2.9E-01 -0.00005 5.9E-01 -0.00006 3.6E-01 Roseburia_hominis UniRef90_G2T2N3 Cluster: ZnF_CHCC domain-containing protein 0.87 0.00009 2.5E-01 5.5E-01 0.00021 6.5E-02 0.00006 3.9E-01 0.00024 7.2E-02 -0.00002 7.9E-01 Roseburia_hominis UniRef90_D4L0U0 Cluster: XRE family transcriptional regulator 0.72 -0.00006 2.6E-01 5.5E-01 0.00006 5.0E-01 -0.00007 2.3E-01 0.00011 2.5E-01 -0.00006 4.0E-01 Roseburia_hominis UniRef90_G2T0G5 Cluster: Peptidase C51 domain-containing protein 0.87 0.00004 2.7E-01 5.8E-01 0.00005 4.6E-01 -0.00005 2.1E-01 0.00005 5.2E-01 -0.00009 6.8E-02 Roseburia_hominis UniRef90_C4ZGA3 Cluster: Beta-xylosidase 0.87 0.00004 3.0E-01 5.9E-01 -0.00001 8.5E-01 -0.00004 2.7E-01 -0.00005 5.1E-01 -0.00008 9.8E-02 Roseburia_hominis UniRef90_D4K7L5 Cluster: Cardiolipin synthase 0.87 0.00004 3.5E-01 6.7E-01 0.00011 4.6E-02 -0.00001 8.0E-01 0.00004 5.3E-01 -0.00003 5.7E-01 Roseburia_hominis UniRef90_G2T2N6 Cluster: Recombinase domain-containing protein 0.87 0.00006 3.7E-01 6.8E-01 0.00017 1.0E-01 0.00005 5.0E-01 0.00012 3.3E-01 -0.00003 7.1E-01 Roseburia_hominis UniRef90_C9YMF3 Cluster: Addiction module toxin, RelE/StbE family 0.86 0.00004 3.8E-01 7.0E-01 0.00006 4.2E-01 -0.00001 8.8E-01 0.00008 3.4E-01 -0.00004 5.4E-01 Roseburia_hominis UniRef90_C4Z639 Cluster: Bacteriophytochrome cph2 0.87 0.00004 4.0E-01 7.3E-01 0.00000 9.7E-01 -0.00006 2.7E-01 -0.00003 7.7E-01 -0.00006 3.4E-01 Roseburia_hominis UniRef90_G2SWG8 Cluster: Mutator family transposase 0.86 0.00003 4.2E-01 7.4E-01 0.00006 3.6E-01 -0.00003 4.0E-01 -0.00004 5.8E-01 0.00004 4.4E-01 43

Supplementary Data 3a Red meat Red meat Choline intake- Choline UniRef90 Family Detection Plasma TMAO Species Cluster Name intake-FFQ intake-7DDR FFQ intake-7DDR member ID Rate Effect P FDR Effect P Effect P Effect P Effect P Roseburia_hominis UniRef90_D4L1Z0 Cluster: Sigma70_r4_2 domain-containing protein 0.87 0.00004 4.1E-01 7.4E-01 0.00009 2.8E-01 -0.00005 3.8E-01 0.00001 9.4E-01 -0.00002 7.0E-01 Roseburia_hominis UniRef90_G2T4S2 Cluster: HTH cro/C1-type domain-containing protein 0.84 0.00004 4.3E-01 7.4E-01 0.00011 1.5E-01 -0.00002 7.3E-01 -0.00007 4.6E-01 -0.00007 2.0E-01 Roseburia_hominis UniRef90_G2SZY5 Cluster: Protein of uncharacterized function 0.85 0.00003 4.4E-01 7.6E-01 -0.00003 6.6E-01 0.00000 9.9E-01 0.00002 7.6E-01 0.00002 6.0E-01 Roseburia_hominis UniRef90_M4RA63 Cluster: Methyltransferase domain protein 0.87 0.00003 4.5E-01 7.6E-01 0.00012 5.9E-02 -0.00003 4.4E-01 0.00002 7.8E-01 -0.00006 2.2E-01 Roseburia_hominis UniRef90_G2SYU2 Cluster: Transposase IS66 0.69 0.00005 4.7E-01 7.8E-01 0.00018 8.9E-02 -0.00003 6.8E-01 0.00004 7.4E-01 0.00000 9.7E-01 Roseburia_hominis UniRef90_G2SYL4 Cluster: Cyclic di-GMP phosphodiesterase response regulator RpfG 0.87 0.00003 5.1E-01 8.1E-01 0.00002 8.1E-01 -0.00002 6.8E-01 -0.00002 8.0E-01 -0.00001 8.9E-01 Roseburia_hominis UniRef90_D4LS35 Cluster: DNA-binding response regulator 0.81 0.00003 5.0E-01 8.1E-01 0.00018 8.4E-03 0.00001 8.1E-01 0.00027 5.7E-04 0.00002 6.8E-01 Roseburia_hominis UniRef90_D4JMV2 Cluster: DNA binding domain, excisionase family 0.86 0.00004 5.0E-01 8.2E-01 0.00013 1.6E-01 -0.00001 9.2E-01 -0.00011 3.0E-01 -0.00003 6.4E-01 Roseburia_hominis UniRef90_G2SZX5 Cluster: HTH_16 domain-containing protein 0.81 0.00003 5.2E-01 8.2E-01 0.00010 8.8E-02 -0.00001 8.0E-01 0.00002 8.3E-01 -0.00004 4.5E-01 Roseburia_hominis UniRef90_D4L1Z5 Cluster: IstB_IS21 domain-containing protein 0.87 0.00004 5.0E-01 8.2E-01 0.00013 1.1E-01 0.00001 8.9E-01 0.00000 9.6E-01 -0.00002 7.9E-01 Roseburia_hominis UniRef90_G2T3Y3 Cluster: RNA methyltransferase 0.85 -0.00003 5.4E-01 8.3E-01 0.00000 9.9E-01 -0.00003 5.4E-01 0.00001 9.0E-01 -0.00001 8.2E-01 Roseburia_hominis UniRef90_C9YMF4 Cluster: Addiction module antitoxin, RelB/DinJ family 0.82 0.00003 5.6E-01 8.4E-01 0.00007 3.1E-01 -0.00005 2.2E-01 0.00001 9.1E-01 0.00000 9.8E-01 Roseburia_hominis UniRef90_C9YMF0 Cluster: Sigma-24 (Feci) 0.87 0.00004 5.6E-01 8.4E-01 0.00012 2.1E-01 -0.00002 7.7E-01 0.00017 1.3E-01 -0.00001 8.8E-01 Roseburia_hominis UniRef90_G2T0G9 Cluster: Immunoglobulin 0.86 0.00003 5.9E-01 8.5E-01 0.00013 1.2E-01 -0.00006 2.8E-01 -0.00004 6.7E-01 -0.00009 1.8E-01 Roseburia_hominis UniRef90_D4JT30 Cluster: HTH cro/C1-type domain-containing protein 0.86 0.00003 5.9E-01 8.6E-01 0.00004 6.3E-01 -0.00006 3.1E-01 0.00000 9.9E-01 0.00006 3.4E-01 Roseburia_hominis UniRef90_G2SYB5 Cluster: Cell filamentation protein fic, putative 0.80 0.00003 6.0E-01 8.6E-01 -0.00003 7.3E-01 -0.00006 2.5E-01 -0.00010 2.8E-01 -0.00012 5.7E-02 Roseburia_hominis UniRef90_D4L0T9 Cluster: Methylglyoxal synthase 0.22 -0.00003 6.9E-01 8.6E-01 -0.00004 6.6E-01 -0.00013 5.5E-02 -0.00012 2.8E-01 -0.00012 1.3E-01 Roseburia_hominis UniRef90_G2T373 Cluster: HTH_17 domain-containing protein 0.77 0.00002 6.9E-01 8.7E-01 0.00006 4.5E-01 -0.00007 1.7E-01 -0.00002 8.6E-01 -0.00003 6.2E-01 Roseburia_hominis UniRef90_C4ZFD9 Cluster: DNA-binding response regulator 0.87 0.00002 7.0E-01 8.7E-01 0.00013 6.6E-02 -0.00003 5.6E-01 -0.00005 5.3E-01 -0.00005 3.5E-01 Roseburia_hominis UniRef90_C4Z798 Cluster: Thioredoxin domain-containing protein 0.87 0.00002 6.2E-01 8.7E-01 0.00005 3.9E-01 -0.00003 3.8E-01 -0.00001 9.3E-01 -0.00005 2.3E-01 Roseburia_hominis UniRef90_C4ZFF1 Cluster: Relaxasome subunit MobC 0.86 0.00002 6.7E-01 8.7E-01 0.00000 9.7E-01 -0.00002 7.4E-01 -0.00006 4.9E-01 -0.00008 1.4E-01 Roseburia_hominis UniRef90_D4JN77 Cluster: HTH cro/C1-type domain-containing protein 0.87 -0.00002 6.5E-01 8.8E-01 0.00004 6.0E-01 -0.00003 6.0E-01 -0.00006 5.5E-01 -0.00013 3.1E-02 Roseburia_hominis UniRef90_C9YMF5 Cluster: Cys_rich_VLP domain-containing protein 0.86 -0.00002 6.4E-01 8.8E-01 0.00017 4.1E-02 0.00002 7.7E-01 0.00010 3.2E-01 0.00001 9.2E-01 Roseburia_hominis UniRef90_D4KMS5 Cluster: Phage_rep_org_N domain-containing protein 0.87 0.00002 6.5E-01 8.8E-01 0.00005 4.2E-01 0.00000 1.0E+00 0.00010 2.1E-01 -0.00009 8.7E-02 Roseburia_hominis UniRef90_D6DJL9 Cluster: DNA primase 0.86 0.00002 6.7E-01 8.8E-01 0.00008 2.5E-01 -0.00002 6.6E-01 0.00005 5.8E-01 -0.00005 3.7E-01 Roseburia_hominis UniRef90_G2SYW8 Cluster: Cyclic lactone autoinducer peptide 0.61 0.00003 6.6E-01 8.8E-01 0.00002 8.3E-01 -0.00008 1.6E-01 0.00005 6.0E-01 -0.00002 7.9E-01 Roseburia_hominis UniRef90_G2T369 Cluster: Macrolide transporter ATP-binding /permease protein 0.86 -0.00002 6.3E-01 8.8E-01 0.00009 1.7E-01 0.00001 8.1E-01 0.00007 3.4E-01 -0.00002 6.5E-01 Roseburia_hominis UniRef90_C4ZE14 Cluster: LexA repressor 0.86 -0.00002 7.1E-01 8.8E-01 -0.00003 7.1E-01 -0.00005 3.8E-01 0.00009 3.1E-01 -0.00009 1.2E-01 Roseburia_hominis UniRef90_O52836 Cluster: Tetracycline resistance protein TetW 0.87 0.00002 7.2E-01 8.8E-01 0.00011 1.8E-01 -0.00002 6.5E-01 0.00009 3.5E-01 -0.00004 5.6E-01 Roseburia_hominis UniRef90_D4L313 Cluster: Group II intron reverse transcriptase/maturase 0.86 0.00002 6.4E-01 8.8E-01 0.00004 5.7E-01 0.00002 6.8E-01 0.00000 9.7E-01 -0.00002 7.4E-01 Roseburia_hominis UniRef90_D4JN79 Cluster: Protein of uncharacterized function (DUF3847) 0.86 -0.00002 7.3E-01 8.8E-01 0.00002 7.5E-01 -0.00003 5.9E-01 -0.00007 4.0E-01 -0.00009 1.3E-01 Roseburia_hominis UniRef90_D4L066 Cluster: HTH cro/C1-type domain-containing protein 0.84 0.00003 7.3E-01 8.9E-01 0.00003 7.5E-01 -0.00010 2.2E-01 0.00007 6.1E-01 -0.00007 4.1E-01 Roseburia_hominis UniRef90_D4JD91 Cluster: MobA_MobL domain-containing protein 0.86 0.00001 7.5E-01 8.9E-01 0.00009 1.8E-01 -0.00004 4.2E-01 -0.00005 5.2E-01 -0.00002 6.4E-01 Roseburia_hominis UniRef90_G2T0F1 Cluster: ABC transporter, ATP-binding protein 0.85 0.00001 7.6E-01 8.9E-01 0.00000 9.8E-01 0.00001 7.4E-01 0.00004 5.8E-01 -0.00006 1.5E-01 Roseburia_hominis UniRef90_G2SZX1 Cluster: MafF protein 0.78 0.00002 8.2E-01 9.1E-01 0.00002 8.1E-01 -0.00013 4.5E-02 0.00009 4.2E-01 -0.00012 1.2E-01 Roseburia_hominis UniRef90_D4JN76 Cluster: Site-specific integrase 0.87 0.00001 7.9E-01 9.2E-01 -0.00003 7.0E-01 -0.00006 2.5E-01 -0.00014 1.4E-01 -0.00011 6.0E-02 Roseburia_hominis UniRef90_D4LZR7 Cluster: HTH cro/C1-type domain-containing protein 0.86 -0.00001 8.1E-01 9.2E-01 0.00005 4.2E-01 -0.00005 2.7E-01 -0.00009 2.2E-01 -0.00004 4.7E-01 Roseburia_hominis UniRef90_D4KSZ4 Cluster: Antitoxin 0.80 -0.00001 8.3E-01 9.3E-01 0.00006 3.3E-01 0.00001 9.1E-01 -0.00002 8.2E-01 -0.00009 8.8E-02 Roseburia_hominis UniRef90_D4JMV4 Cluster: Tyrosine recombinase XerC 0.87 -0.00001 8.0E-01 9.3E-01 0.00011 1.2E-01 -0.00004 3.4E-01 -0.00002 8.4E-01 -0.00002 6.9E-01 Roseburia_hominis UniRef90_G2T5C3 Cluster: Toxin-antitoxin system protein 0.86 0.00001 8.6E-01 9.5E-01 -0.00002 8.4E-01 -0.00006 4.4E-01 -0.00023 6.7E-02 -0.00012 1.7E-01 Roseburia_hominis UniRef90_G2T4R6 Cluster: Glutamyl-tRNA amidotransferase 0.81 0.00001 8.9E-01 9.5E-01 0.00007 2.6E-01 0.00004 3.5E-01 -0.00006 4.1E-01 -0.00007 1.7E-01 Roseburia_hominis UniRef90_G2SYP3 Cluster: HTH cro/C1-type domain-containing protein 0.79 0.00000 9.5E-01 9.9E-01 0.00007 4.4E-01 0.00002 6.9E-01 0.00017 9.4E-02 -0.00005 5.1E-01 Roseburia_hominis UniRef90_G2T474 Cluster: Uncharacterized protein 0.86 0.00035 9.4E-04 2.3E-02 -0.00002 9.1E-01 -0.00014 2.1E-01 -0.00005 8.0E-01 -0.00013 3.2E-01 Roseburia_hominis UniRef90_G2T2C6 Cluster: Uncharacterized protein 0.74 0.00032 8.2E-04 2.4E-02 0.00007 5.9E-01 -0.00013 2.0E-01 0.00000 9.9E-01 -0.00011 3.3E-01 Roseburia_hominis UniRef90_G2SYK2 Cluster: Uncharacterized protein 0.70 0.00028 2.8E-04 2.6E-02 0.00000 9.6E-01 -0.00005 5.5E-01 0.00001 9.7E-01 -0.00011 2.3E-01 Roseburia_hominis UniRef90_G2T5G8 Cluster: Uncharacterized protein 0.80 0.00014 1.4E-03 3.3E-02 0.00001 8.5E-01 -0.00002 6.7E-01 -0.00006 4.4E-01 -0.00001 8.9E-01 Roseburia_hominis UniRef90_G2T377 Cluster: Uncharacterized protein 0.78 0.00016 3.8E-03 4.6E-02 -0.00002 7.6E-01 -0.00004 5.1E-01 0.00010 2.9E-01 0.00002 7.6E-01 Roseburia_hominis UniRef90_G2T2J8 Cluster: Uncharacterized protein 0.77 0.00025 1.1E-02 7.6E-02 -0.00003 8.4E-01 -0.00007 4.8E-01 -0.00011 5.4E-01 -0.00012 2.9E-01 Roseburia_hominis unknown Unknown gene identity 0.87 0.00051 1.9E-02 1.1E-01 0.00020 5.4E-01 -0.00020 3.7E-01 0.00006 8.7E-01 -0.00026 3.2E-01 Roseburia_hominis UniRef90_D4K3L0 Cluster: Uncharacterized protein 0.86 0.00010 2.5E-02 1.3E-01 0.00000 9.5E-01 -0.00001 8.9E-01 0.00005 5.6E-01 0.00000 9.4E-01 Roseburia_hominis UniRef90_G2T3T4 Cluster: Uncharacterized protein 0.81 0.00009 3.5E-02 1.7E-01 -0.00005 4.6E-01 -0.00001 7.5E-01 -0.00001 8.9E-01 -0.00003 5.9E-01 Roseburia_hominis UniRef90_G2T625 Cluster: Uncharacterized protein 0.49 0.00012 4.2E-02 1.8E-01 0.00013 9.1E-02 -0.00006 2.8E-01 -0.00003 7.5E-01 0.00002 7.9E-01 Roseburia_hominis UniRef90_G2SYK1 Cluster: Uncharacterized protein 0.53 0.00023 5.4E-02 2.2E-01 0.00009 5.8E-01 -0.00020 9.7E-02 0.00003 8.7E-01 -0.00021 1.4E-01 Roseburia_hominis UniRef90_G2SZX8 Cluster: Uncharacterized protein 0.86 0.00013 6.6E-02 2.3E-01 0.00006 5.6E-01 0.00001 8.7E-01 0.00012 3.2E-01 -0.00010 2.0E-01 Roseburia_hominis UniRef90_G2T5J9 Cluster: Uncharacterized protein 0.85 0.00009 9.2E-02 2.8E-01 0.00002 7.8E-01 -0.00003 6.0E-01 0.00003 7.0E-01 0.00006 3.0E-01 Roseburia_hominis UniRef90_G2T4U2 Cluster: Uncharacterized protein 0.60 0.00009 9.1E-02 2.8E-01 0.00014 6.6E-02 -0.00002 7.4E-01 0.00016 8.0E-02 0.00007 2.7E-01 Roseburia_hominis UniRef90_G2T4P1 Cluster: Uncharacterized protein 0.79 -0.00008 9.4E-02 2.9E-01 -0.00001 8.5E-01 0.00000 9.4E-01 0.00010 2.3E-01 0.00001 9.2E-01 Roseburia_hominis UniRef90_G2SYA8 Cluster: Uncharacterized protein 0.86 0.00007 1.0E-01 3.0E-01 0.00019 2.3E-03 -0.00001 8.6E-01 0.00018 1.5E-02 0.00005 3.6E-01 Roseburia_hominis UniRef90_G2T3B0 Cluster: Uncharacterized protein 0.82 0.00007 1.0E-01 3.1E-01 0.00011 9.1E-02 0.00001 8.8E-01 0.00008 3.0E-01 0.00002 7.4E-01 Roseburia_hominis UniRef90_G2SZW6 Cluster: Uncharacterized protein 0.86 0.00008 1.1E-01 3.3E-01 0.00011 1.1E-01 -0.00003 5.7E-01 0.00005 5.2E-01 -0.00004 5.1E-01 Roseburia_hominis UniRef90_G2SYW2 Cluster: Uncharacterized protein 0.83 0.00007 1.2E-01 3.5E-01 0.00008 2.0E-01 -0.00005 2.5E-01 0.00007 4.0E-01 -0.00004 4.9E-01 Roseburia_hominis UniRef90_G2SY25 Cluster: Uncharacterized protein 0.73 -0.00007 1.5E-01 3.9E-01 -0.00008 2.6E-01 0.00000 9.4E-01 0.00001 9.5E-01 -0.00005 4.2E-01 Roseburia_hominis UniRef90_G2T4S0 Cluster: Uncharacterized protein 0.57 -0.00014 1.5E-01 3.9E-01 -0.00006 6.3E-01 -0.00015 1.2E-01 -0.00010 5.2E-01 -0.00023 3.7E-02 Roseburia_hominis UniRef90_G2T2N0 Cluster: Uncharacterized protein 0.86 0.00010 1.5E-01 3.9E-01 0.00023 2.5E-02 0.00004 5.5E-01 0.00018 1.4E-01 -0.00008 3.2E-01 44

Supplementary Data 3a Red meat Red meat Choline intake- Choline UniRef90 Family Detection Plasma TMAO Species Cluster Name intake-FFQ intake-7DDR FFQ intake-7DDR member ID Rate Effect P FDR Effect P Effect P Effect P Effect P Roseburia_hominis UniRef90_G2T398 Cluster: Uncharacterized protein 0.74 0.00008 1.6E-01 4.1E-01 -0.00005 4.4E-01 -0.00008 1.7E-01 -0.00010 2.6E-01 -0.00012 5.1E-02 Roseburia_hominis UniRef90_G2T0G6 Cluster: Uncharacterized protein 0.82 0.00006 1.7E-01 4.2E-01 0.00015 3.8E-02 -0.00002 6.3E-01 0.00007 4.3E-01 -0.00008 1.5E-01 Roseburia_hominis UniRef90_C4Z371 Cluster: Uncharacterized protein 0.71 -0.00009 1.7E-01 4.2E-01 -0.00002 8.8E-01 -0.00005 4.4E-01 -0.00005 6.8E-01 -0.00015 6.5E-02 Roseburia_hominis UniRef90_C4ZEA9 Cluster: Uncharacterized protein 0.86 -0.00009 1.8E-01 4.4E-01 -0.00002 8.6E-01 -0.00004 5.5E-01 -0.00005 6.3E-01 -0.00012 1.1E-01 Roseburia_hominis UniRef90_G2T3A0 Cluster: Uncharacterized protein 0.60 0.00008 1.8E-01 4.4E-01 -0.00004 6.4E-01 0.00004 4.8E-01 0.00003 7.5E-01 -0.00014 5.6E-02 Roseburia_hominis UniRef90_H1AJE1 Unknown - Obsolete ID 0.87 0.00006 2.2E-01 5.0E-01 0.00010 1.7E-01 -0.00001 8.0E-01 0.00007 4.2E-01 -0.00001 8.3E-01 Roseburia_hominis UniRef90_G2T4T9 Cluster: Uncharacterized protein 0.83 0.00006 2.3E-01 5.1E-01 0.00019 8.6E-03 0.00000 9.3E-01 0.00030 5.5E-04 0.00002 7.2E-01 Roseburia_hominis UniRef90_D4J5S1 Cluster: Uncharacterized protein 0.87 0.00004 2.4E-01 5.3E-01 0.00012 3.9E-02 0.00002 6.5E-01 0.00007 2.9E-01 0.00001 8.1E-01 Roseburia_hominis UniRef90_G2SYN5 Cluster: Uncharacterized protein 0.67 0.00006 2.4E-01 5.3E-01 0.00009 2.7E-01 0.00002 7.5E-01 0.00000 9.6E-01 -0.00004 5.2E-01 Roseburia_hominis UniRef90_C4ZFD5 Cluster: Uncharacterized protein 0.78 0.00008 2.6E-01 5.5E-01 0.00007 4.8E-01 0.00001 8.6E-01 -0.00014 2.7E-01 -0.00008 3.3E-01 Roseburia_hominis UniRef90_G2SYL9 Cluster: Uncharacterized protein 0.86 0.00008 2.7E-01 5.8E-01 -0.00013 2.1E-01 -0.00009 1.8E-01 -0.00015 2.2E-01 -0.00019 2.4E-02 Roseburia_hominis UniRef90_C9YME0 Cluster: Uncharacterized protein 0.86 0.00006 2.7E-01 5.8E-01 0.00002 7.6E-01 -0.00009 8.5E-02 -0.00003 7.6E-01 -0.00007 2.5E-01 Roseburia_hominis UniRef90_G2SY28 Cluster: Uncharacterized protein 0.84 0.00005 2.8E-01 5.9E-01 0.00004 6.0E-01 -0.00002 6.9E-01 -0.00002 8.6E-01 -0.00001 8.1E-01 Roseburia_hominis UniRef90_C4ZE46 Cluster: Uncharacterized protein 0.87 0.00006 2.9E-01 5.9E-01 0.00007 4.3E-01 -0.00004 4.9E-01 0.00010 3.2E-01 -0.00006 3.8E-01 Roseburia_hominis UniRef90_G2T0G2 Cluster: Uncharacterized protein 0.86 0.00006 2.9E-01 5.9E-01 0.00006 4.2E-01 -0.00007 1.8E-01 0.00002 8.3E-01 -0.00014 2.9E-02 Roseburia_hominis UniRef90_G2T0H1 Cluster: Uncharacterized protein 0.66 0.00005 3.0E-01 6.0E-01 0.00000 9.5E-01 0.00000 9.6E-01 0.00011 2.0E-01 -0.00001 8.3E-01 Roseburia_hominis UniRef90_C9YME1 Cluster: Uncharacterized protein 0.86 0.00007 3.0E-01 6.0E-01 0.00021 4.2E-02 -0.00003 6.8E-01 0.00008 5.1E-01 0.00000 9.6E-01 Roseburia_hominis UniRef90_G2SYN6 Cluster: Uncharacterized protein 0.78 0.00005 3.2E-01 6.2E-01 0.00002 7.5E-01 -0.00006 2.5E-01 -0.00001 9.4E-01 -0.00006 2.9E-01 Roseburia_hominis UniRef90_G2T2N4 Cluster: Uncharacterized protein 0.87 0.00005 3.4E-01 6.5E-01 0.00014 7.7E-02 0.00003 5.7E-01 0.00012 2.0E-01 -0.00004 5.7E-01 Roseburia_hominis UniRef90_T1Z5B5 Unknown - Obsolete ID 0.87 0.00004 3.5E-01 6.7E-01 0.00006 3.0E-01 0.00000 9.4E-01 0.00004 5.4E-01 -0.00005 3.1E-01 Roseburia_hominis UniRef90_G2T4A6 Cluster: Uncharacterized protein 0.62 0.00006 3.6E-01 6.8E-01 0.00007 4.2E-01 0.00004 5.9E-01 0.00002 8.3E-01 -0.00006 4.8E-01 Roseburia_hominis UniRef90_G2T381 Cluster: Uncharacterized protein 0.80 0.00005 4.1E-01 7.3E-01 -0.00008 3.5E-01 -0.00006 3.0E-01 0.00001 9.6E-01 -0.00008 2.7E-01 Roseburia_hominis UniRef90_G2SYR3 Cluster: Uncharacterized protein 0.53 0.00005 4.1E-01 7.4E-01 -0.00001 8.8E-01 -0.00003 6.2E-01 0.00005 5.8E-01 0.00008 2.5E-01 Roseburia_hominis UniRef90_C4ZEC2 Cluster: Uncharacterized protein 0.86 -0.00005 4.3E-01 7.4E-01 0.00000 9.8E-01 -0.00003 6.4E-01 -0.00009 4.2E-01 -0.00010 1.9E-01 Roseburia_hominis UniRef90_G2T5G5 Cluster: Uncharacterized protein 0.81 0.00005 4.6E-01 7.9E-01 0.00005 6.3E-01 -0.00002 8.2E-01 -0.00016 1.8E-01 -0.00008 3.4E-01 Roseburia_hominis UniRef90_G2T4S1 Cluster: Uncharacterized protein 0.85 0.00003 4.7E-01 7.9E-01 0.00007 3.3E-01 0.00000 9.4E-01 0.00002 7.8E-01 -0.00006 2.4E-01 Roseburia_hominis UniRef90_C4ZEQ7 Cluster: Uncharacterized protein 0.74 0.00003 4.9E-01 8.2E-01 0.00012 1.1E-01 -0.00002 7.5E-01 0.00010 2.1E-01 0.00003 5.6E-01 Roseburia_hominis UniRef90_D6E4B0 Cluster: Uncharacterized protein 0.86 -0.00004 4.9E-01 8.2E-01 -0.00005 5.1E-01 -0.00004 4.4E-01 -0.00001 8.8E-01 -0.00005 3.9E-01 Roseburia_hominis UniRef90_G2T2N5 Cluster: Uncharacterized protein 0.84 0.00004 5.5E-01 8.3E-01 0.00012 1.4E-01 0.00002 6.8E-01 0.00010 3.2E-01 -0.00004 5.4E-01 Roseburia_hominis UniRef90_G2SYW1 Cluster: Uncharacterized protein 0.84 0.00003 5.6E-01 8.4E-01 0.00010 2.1E-01 -0.00007 2.0E-01 -0.00004 7.0E-01 0.00003 6.1E-01 Roseburia_hominis UniRef90_G2T0H5 Cluster: Uncharacterized protein 0.85 0.00002 5.6E-01 8.4E-01 0.00014 1.8E-02 -0.00001 8.9E-01 0.00012 8.9E-02 -0.00005 3.1E-01 Roseburia_hominis UniRef90_T4GS85 Unknown - Obsolete ID 0.86 0.00004 5.7E-01 8.4E-01 0.00024 1.0E-02 0.00005 4.5E-01 0.00016 1.4E-01 -0.00004 5.9E-01 Roseburia_hominis UniRef90_G2SY36 Cluster: Uncharacterized protein 0.86 0.00003 6.1E-01 8.6E-01 0.00006 4.4E-01 -0.00001 9.0E-01 -0.00005 5.9E-01 -0.00013 3.4E-02 Roseburia_hominis UniRef90_G2SYV8 Cluster: Uncharacterized protein 0.85 0.00003 6.0E-01 8.6E-01 0.00008 3.5E-01 -0.00001 8.5E-01 0.00005 6.3E-01 -0.00002 7.4E-01 Roseburia_hominis UniRef90_G2T3Y4 Cluster: Uncharacterized protein 0.19 0.00004 5.9E-01 8.7E-01 -0.00008 4.2E-01 -0.00002 7.5E-01 0.00010 4.2E-01 -0.00009 2.4E-01 Roseburia_hominis UniRef90_G2SY33 Cluster: Uncharacterized protein 0.86 0.00002 6.8E-01 8.7E-01 -0.00002 7.7E-01 -0.00001 8.2E-01 -0.00006 4.9E-01 -0.00017 9.3E-03 Roseburia_hominis UniRef90_G2SY34 Cluster: Uncharacterized protein 0.87 0.00002 6.8E-01 8.7E-01 -0.00005 5.6E-01 -0.00006 3.3E-01 -0.00010 3.2E-01 -0.00010 1.5E-01 Roseburia_hominis UniRef90_G2SYR0 Cluster: Uncharacterized protein 0.43 0.00003 6.7E-01 8.7E-01 -0.00005 6.8E-01 0.00000 9.9E-01 0.00012 3.7E-01 0.00011 2.5E-01 Roseburia_hominis UniRef90_G2T5C4 Cluster: Uncharacterized protein 0.86 -0.00002 7.0E-01 8.7E-01 -0.00008 3.0E-01 -0.00005 2.9E-01 0.00000 9.9E-01 -0.00014 1.9E-02 Roseburia_hominis UniRef90_G2SY29 Cluster: Uncharacterized protein 0.86 0.00003 6.6E-01 8.7E-01 0.00001 8.7E-01 -0.00004 5.2E-01 -0.00002 8.6E-01 -0.00005 4.7E-01 Roseburia_hominis UniRef90_C4ZE42 Cluster: Uncharacterized protein 0.82 0.00002 6.4E-01 8.7E-01 -0.00007 3.6E-01 -0.00002 6.3E-01 0.00004 6.8E-01 -0.00001 8.5E-01 Roseburia_hominis UniRef90_G2T4R8 Cluster: Uncharacterized protein 0.72 0.00002 6.7E-01 8.7E-01 0.00008 2.4E-01 -0.00005 3.4E-01 -0.00009 2.8E-01 -0.00007 2.2E-01 Roseburia_hominis UniRef90_G2T5F9 Cluster: Uncharacterized protein 0.85 0.00002 6.6E-01 8.8E-01 0.00012 1.3E-01 -0.00009 9.6E-02 -0.00002 8.2E-01 -0.00006 3.5E-01 Roseburia_hominis UniRef90_G2T3A2 Cluster: Uncharacterized protein 0.86 -0.00002 6.4E-01 8.8E-01 0.00011 1.3E-01 -0.00003 5.2E-01 -0.00001 8.9E-01 -0.00003 6.1E-01 Roseburia_hominis UniRef90_G2T4R5 Cluster: Uncharacterized protein 0.82 0.00002 7.3E-01 8.9E-01 0.00009 1.8E-01 -0.00005 2.8E-01 0.00001 8.8E-01 -0.00005 3.4E-01 Roseburia_hominis UniRef90_C4ZEC1 Cluster: Uncharacterized protein 0.87 0.00002 7.6E-01 8.9E-01 0.00001 8.6E-01 -0.00002 7.8E-01 0.00004 7.1E-01 -0.00010 1.6E-01 Roseburia_hominis UniRef90_G2T4V3 Cluster: Uncharacterized protein 0.54 -0.00002 7.8E-01 9.1E-01 0.00013 1.3E-01 0.00001 8.7E-01 0.00013 1.8E-01 0.00011 1.1E-01 Roseburia_hominis UniRef90_G2T5G4 Cluster: Uncharacterized protein 0.85 -0.00002 8.0E-01 9.2E-01 0.00005 6.0E-01 -0.00007 2.9E-01 0.00008 4.7E-01 -0.00008 3.1E-01 Roseburia_hominis UniRef90_B6FNP2 Unknown - Obsolete ID 0.84 -0.00001 8.5E-01 9.4E-01 0.00029 4.6E-03 0.00002 7.8E-01 0.00004 7.6E-01 0.00002 7.8E-01 Roseburia_hominis UniRef90_G2SYR5 Cluster: Uncharacterized protein 0.53 -0.00001 8.9E-01 9.6E-01 0.00008 3.2E-01 0.00001 8.7E-01 0.00007 4.2E-01 0.00014 2.0E-02 Roseburia_hominis UniRef90_G2T4R1 Cluster: Uncharacterized protein 0.72 0.00001 9.2E-01 9.7E-01 0.00004 5.8E-01 -0.00006 1.8E-01 0.00001 8.8E-01 -0.00009 1.2E-01 Roseburia_hominis UniRef90_D4KJZ4 Cluster: Uncharacterized protein 0.86 0.00001 9.2E-01 9.7E-01 0.00003 7.3E-01 -0.00004 4.8E-01 -0.00013 1.8E-01 -0.00006 3.6E-01 Roseburia_hominis UniRef90_G2T3B4 Cluster: Uncharacterized protein 0.70 0.00002 9.2E-01 9.8E-01 0.00031 2.6E-01 -0.00032 9.5E-02 0.00009 7.8E-01 -0.00006 8.0E-01 Roseburia_hominis UniRef90_C4Z3R8 Cluster: Uncharacterized protein 0.84 0.00000 9.3E-01 9.8E-01 0.00006 3.7E-01 0.00000 9.9E-01 0.00002 7.9E-01 -0.00007 2.7E-01 Roseburia_hominis UniRef90_G2SYR2 Cluster: Uncharacterized protein 0.60 0.00000 9.5E-01 9.8E-01 0.00003 7.1E-01 -0.00006 3.1E-01 0.00002 8.5E-01 0.00011 7.9E-02 Roseburia_hominis UniRef90_G2T4V9 Cluster: Uncharacterized protein 0.60 0.00000 9.8E-01 9.9E-01 0.00012 1.2E-01 0.00006 2.8E-01 0.00021 2.5E-02 0.00012 5.8E-02 Roseburia_hominis UniRef90_G2T3B5 Cluster: Uncharacterized protein 0.86 0.00000 9.8E-01 9.9E-01 0.00007 3.3E-01 -0.00002 6.8E-01 0.00006 4.6E-01 0.00001 9.0E-01

Supplementary Data 3b Supplementary Data 3b. Association of transcriptions of gene clusters (RNA/DNA ratio) within TMAO-associated species with plasma TMAO levels, and intakes of choline and red meat. Full model was adjusted for age, BMI, physical activity, energy intake, smoking, cumulative dietary quality (since 1986), antibiotics use, probiotics use, the Bristol Stool Chart, and/or fish intake (for non-fish dietary variables). UniRef90 Family Plasma TMAO Red meat Red meat Choline Choline Species Cluster Name Detection member ID Rate Effect P FDR Effect P Effect P Effect P Effect P Alistipes_shahii UniRef90_D4IKD1 Cluster: Copper homeostasis protein CutC 0.10 0.0908 2.3E-04 6.3E-02 0.0719 2.1E-01 0.0039 7.9E-01 0.0175 7.2E-01 0.0208 5.1E-01 Alistipes_shahii UniRef90_D4IJX8 Cluster: tRNA dimethylallyltransferase 0.11 0.0835 6.8E-04 7.7E-02 0.0477 3.9E-01 -0.0118 4.1E-01 0.0402 4.0E-01 -0.0340 2.8E-01 Alistipes_shahii UniRef90_D4IQE1 Cluster: Nicotinate-nucleotide diphosphorylase (Carboxylating) 0.12 0.0764 3.2E-03 1.4E-01 0.1057 7.1E-02 -0.0037 8.1E-01 0.1244 1.2E-02 0.0281 4.0E-01 Alistipes_shahii UniRef90_I3YM42 Cluster: 30S ribosomal protein S11 0.19 0.1465 3.5E-03 1.4E-01 0.0860 4.6E-01 0.0019 9.5E-01 0.1599 1.0E-01 0.0743 2.4E-01 Alistipes_shahii UniRef90_I3YNF1 Cluster: Succinate dehydrogenase subunit B 0.18 0.1127 4.7E-03 1.6E-01 -0.0387 6.7E-01 -0.0283 2.3E-01 -0.0221 7.7E-01 -0.0747 1.4E-01 Alistipes_shahii UniRef90_D4IIN0 Cluster: SusD family 0.13 0.1175 5.4E-03 1.7E-01 -0.0779 4.2E-01 0.0150 5.4E-01 0.0293 7.2E-01 -0.0250 6.3E-01 Alistipes_shahii UniRef90_D4IJD5 Cluster: Acetyl/propionyl-CoA carboxylase, alpha subunit 0.15 0.1105 9.8E-03 2.2E-01 -0.0820 4.1E-01 -0.0384 1.3E-01 0.0159 8.5E-01 -0.0156 7.8E-01 Alistipes_shahii UniRef90_D4INF9 Cluster: Permeases of the drug/metabolite transporter (DMT) superfamily 0.15 0.1021 1.0E-02 2.2E-01 0.1072 2.5E-01 -0.0065 7.8E-01 -0.0090 9.1E-01 -0.0866 7.8E-02 Alistipes_shahii UniRef90_D4IPV6 Cluster: Corrinoid adenosyltransferase 0.11 0.0741 1.1E-02 2.2E-01 0.1384 3.5E-02 0.0009 9.6E-01 0.0791 1.6E-01 0.0125 7.3E-01 Alistipes_shahii UniRef90_D4INQ3 Cluster: DNA repair protein RecN 0.17 0.0659 1.2E-02 2.3E-01 0.0167 7.8E-01 -0.0184 2.5E-01 0.0648 2.1E-01 0.0204 5.5E-01 Alistipes_shahii UniRef90_D4ILS3 Cluster: 50S ribosomal protein L35 0.21 0.1957 1.2E-02 2.3E-01 0.0384 8.3E-01 -0.0046 9.2E-01 0.0100 9.5E-01 -0.0352 7.2E-01 Alistipes_shahii UniRef90_I3YMN3 Cluster: SusE domain-containing protein 0.14 0.1171 1.2E-02 2.2E-01 -0.1210 2.6E-01 -0.0060 8.2E-01 0.0006 1.0E+00 -0.0979 9.2E-02 Alistipes_shahii UniRef90_D4IK25 Cluster: 2-oxoglutarate oxidoreductase subunit KorA 0.20 0.1218 1.2E-02 2.2E-01 0.0963 4.0E-01 -0.0098 7.3E-01 0.0557 5.6E-01 -0.0614 3.1E-01 Alistipes_shahii UniRef90_R6Y4C7 Cluster: DNA-binding protein 0.15 0.1520 1.3E-02 2.3E-01 0.0810 5.7E-01 0.0135 7.0E-01 0.0079 9.5E-01 -0.0903 2.4E-01 Alistipes_shahii UniRef90_R6WYT0 Cluster: TonB-linked outer membrane protein SusC/RagA family 0.13 0.1035 1.4E-02 2.3E-01 -0.1287 1.9E-01 0.0031 9.0E-01 0.0146 8.6E-01 -0.0748 1.6E-01 Alistipes_shahii UniRef90_D4IN34 Cluster: RteC protein 0.15 0.0473 1.5E-02 2.4E-01 0.0242 5.9E-01 -0.0053 6.5E-01 0.0223 5.6E-01 0.0059 8.2E-01 Alistipes_shahii UniRef90_R5UF02 Cluster: 3-oxoacyl-[acyl-carrier-protein] reductase 0.21 0.1144 1.7E-02 2.5E-01 0.0054 9.6E-01 -0.0219 4.3E-01 0.0693 4.5E-01 -0.0258 6.7E-01 Alistipes_shahii UniRef90_D4IJ02 Cluster: Protein-export membrane protein SecG 0.15 0.1049 1.8E-02 2.6E-01 0.0938 3.5E-01 -0.0146 5.8E-01 0.0549 5.2E-01 -0.0114 8.4E-01 Alistipes_shahii UniRef90_D4IIM8 Cluster: Alpha-amylase 0.13 0.0869 1.8E-02 2.6E-01 -0.0622 4.7E-01 0.0007 9.7E-01 0.0104 8.8E-01 -0.1247 6.1E-03 Alistipes_shahii UniRef90_D4IMJ6 Cluster: 50S ribosomal protein L22 0.18 0.1285 1.9E-02 2.7E-01 0.0723 5.7E-01 -0.0097 7.6E-01 -0.0632 5.5E-01 -0.0081 9.1E-01 Alistipes_shahii UniRef90_D4IJM3 Cluster: Histone H1-like protein Hc1 0.14 0.1283 2.1E-02 2.8E-01 -0.0587 6.5E-01 -0.0128 6.9E-01 0.0462 6.6E-01 -0.0249 7.2E-01 Alistipes_shahii UniRef90_I3YM34 Cluster: 30S ribosomal protein S5 0.21 0.1339 2.1E-02 2.9E-01 0.1268 3.4E-01 0.0139 6.9E-01 0.1044 3.5E-01 -0.0177 8.1E-01 Alistipes_shahii UniRef90_D4IMG6 Cluster: Signal transduction histidine kinase 0.16 0.0687 2.3E-02 2.9E-01 0.1182 8.0E-02 -0.0116 5.2E-01 -0.0151 7.9E-01 -0.0309 4.2E-01 Alistipes_shahii UniRef90_D4IJL6 Cluster: Aminotransferase 0.18 0.0735 2.3E-02 2.8E-01 0.0597 4.2E-01 -0.0179 3.4E-01 0.0671 2.8E-01 -0.0426 2.9E-01 Alistipes_shahii UniRef90_D4ILQ1 Cluster: Putative fluoride ion transporter CrcB 0.13 0.1126 2.5E-02 2.9E-01 0.0543 6.3E-01 0.0067 8.2E-01 0.0223 8.1E-01 -0.0658 2.9E-01 Alistipes_shahii UniRef90_R7JKW6 Cluster: 60 kDa chaperonin 0.23 0.1241 2.6E-02 2.9E-01 0.1170 3.7E-01 -0.0342 2.8E-01 0.1674 1.2E-01 -0.0056 9.4E-01 Alistipes_shahii UniRef90_D4IPB0 Cluster: Sugar kinases, ribokinase family 0.15 0.0871 2.6E-02 2.9E-01 0.0815 3.5E-01 -0.0083 7.2E-01 0.0513 4.8E-01 0.0192 7.0E-01 Alistipes_shahii UniRef90_D4IJ82 Cluster: Cold-shock DNA-binding protein family 0.16 0.1295 2.6E-02 2.9E-01 0.1313 3.2E-01 0.0179 6.0E-01 0.1247 2.6E-01 -0.0290 6.9E-01 Alistipes_shahii UniRef90_D4INZ1 Cluster: DNA-binding protein 0.14 0.0752 2.6E-02 2.8E-01 0.1482 5.2E-02 -0.0001 1.0E+00 0.0679 2.9E-01 0.0061 8.9E-01 Alistipes_shahii UniRef90_D4IMJ9 Cluster: 50S ribosomal protein L29 0.15 0.1090 2.6E-02 2.8E-01 0.1315 2.4E-01 0.0027 9.3E-01 0.1111 2.4E-01 0.0042 9.5E-01 Alistipes_shahii UniRef90_D4IND3 Cluster: 50S ribosomal protein L33 0.14 0.1251 2.7E-02 2.8E-01 0.1027 4.2E-01 -0.0031 9.3E-01 0.1362 2.1E-01 0.0848 2.4E-01 Alistipes_shahii UniRef90_D4IPC6 Cluster: Collagenase and related proteases 0.19 0.1037 2.7E-02 2.8E-01 0.1577 1.4E-01 0.0147 5.9E-01 0.0416 6.4E-01 -0.0769 1.9E-01 Alistipes_shahii UniRef90_D4IJ88 Cluster: NADH:flavin oxidoreductases, Old Yellow Enzyme family 0.13 0.0612 2.8E-02 2.8E-01 0.0006 9.9E-01 0.0059 7.2E-01 0.0295 5.8E-01 -0.0115 7.5E-01 Alistipes_shahii UniRef90_D4INH5 Cluster: Recombination protein RecR 0.11 0.0560 2.8E-02 2.8E-01 0.0483 3.9E-01 0.0018 9.1E-01 0.1051 2.9E-02 -0.0280 3.9E-01 Alistipes_shahii UniRef90_I3YME3 Cluster: Ribosomal subunit interface protein 0.14 0.1024 2.8E-02 2.8E-01 -0.0803 4.5E-01 -0.0315 2.4E-01 0.0525 5.5E-01 0.0314 5.9E-01 Alistipes_shahii UniRef90_D4IKA9 Cluster: Carb-bd_dom_fam9 domain-containing protein 0.16 0.1084 2.9E-02 2.8E-01 0.0853 4.5E-01 -0.0054 8.5E-01 0.0674 4.8E-01 0.0120 8.5E-01 Alistipes_shahii UniRef90_D4ILF2 Cluster: Heat shock protein Hsp20 0.16 0.1450 2.9E-02 2.8E-01 -0.0230 8.8E-01 -0.0312 4.1E-01 0.0929 4.6E-01 0.0163 8.4E-01 Alistipes_shahii UniRef90_D4IQR1 Cluster: 50S ribosomal protein L7/L12 0.23 0.1675 2.9E-02 2.7E-01 0.0408 8.2E-01 -0.0277 5.3E-01 -0.0106 9.4E-01 -0.0649 5.0E-01 Alistipes_shahii UniRef90_D4IIR6 Cluster: 5-methylthioadenosine/S-adenosylhomocysteine deaminase 0.14 0.0616 3.0E-02 2.7E-01 0.0756 2.4E-01 -0.0114 4.9E-01 -0.0011 9.8E-01 -0.0371 3.0E-01 Alistipes_shahii UniRef90_D4IK36 Cluster: Dihydrolipoyl dehydrogenase 0.19 0.0915 3.0E-02 2.7E-01 0.0796 4.1E-01 -0.0176 4.7E-01 0.0664 4.1E-01 -0.0165 7.5E-01 Alistipes_shahii UniRef90_I3YLT3 Cluster: tRNA (guanine-N(1)-)-methyltransferase 0.11 0.0470 3.0E-02 2.7E-01 0.0354 4.7E-01 -0.0087 5.1E-01 0.0314 4.5E-01 0.0259 3.6E-01 Alistipes_shahii UniRef90_I3YKT5 Cluster: 30S ribosomal protein S15 0.23 0.2013 3.1E-02 2.7E-01 -0.1098 6.3E-01 -0.0797 1.3E-01 0.0521 7.8E-01 -0.0618 5.9E-01 Alistipes_shahii UniRef90_R6XQ31 Cluster: Peptide chain release factor 3 0.12 0.0358 3.1E-02 2.7E-01 -0.0140 7.1E-01 -0.0061 5.4E-01 0.0334 3.0E-01 0.0246 2.5E-01 Alistipes_shahii UniRef90_D4ILQ7 Cluster: Membrane protein insertase YidC 0.16 0.0478 3.2E-02 2.7E-01 0.0392 4.4E-01 -0.0047 7.2E-01 0.0014 9.7E-01 -0.0134 6.4E-01 Alistipes_shahii UniRef90_D4IKZ3 Cluster: 4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase (flavodoxin) 0.15 0.0451 3.4E-02 2.8E-01 0.0632 2.0E-01 0.0023 8.5E-01 0.0499 2.2E-01 -0.0291 2.7E-01 Alistipes_shahii UniRef90_D4IQN8 Cluster: 5-formyltetrahydrofolate cyclo-ligase 0.11 0.0714 3.7E-02 2.9E-01 0.0024 9.8E-01 0.0058 7.7E-01 0.0827 1.9E-01 -0.0420 3.3E-01 Alistipes_shahii UniRef90_I3YMN1 Cluster: Alpha-amylase 2 0.10 0.0863 3.9E-02 2.9E-01 -0.0459 6.3E-01 0.0049 8.4E-01 -0.0819 3.1E-01 -0.1522 3.4E-03 Alistipes_shahii UniRef90_I3YHN4 Cluster: Transcription termination/antitermination protein NusA 0.19 0.0682 3.9E-02 2.9E-01 0.0834 2.6E-01 0.0128 5.1E-01 0.0353 5.8E-01 0.0103 8.1E-01 Alistipes_shahii UniRef90_D4IND7 Cluster: Signal recognition particle receptor FtsY 0.21 0.0905 3.9E-02 2.9E-01 0.0573 5.8E-01 0.0119 6.4E-01 0.1508 7.7E-02 -0.0392 4.7E-01 Alistipes_shahii UniRef90_D4IL18 Cluster: Transcriptional regulators 0.11 0.0647 3.9E-02 2.9E-01 0.1385 5.4E-02 0.0032 8.6E-01 -0.0023 9.7E-01 0.0205 6.0E-01 Alistipes_shahii UniRef90_D4IPB8 Cluster: Ferredoxin 0.14 0.1344 4.0E-02 2.9E-01 -0.2246 1.2E-01 -0.0748 4.5E-02 -0.1954 1.1E-01 -0.1476 6.7E-02 Alistipes_shahii UniRef90_I3YR79 Cluster: 2-oxoglutarate ferredoxin oxidoreductase, gamma subunit 0.19 0.0794 4.0E-02 2.9E-01 0.0545 5.4E-01 -0.0207 3.6E-01 0.0051 9.5E-01 -0.0091 8.5E-01 Alistipes_shahii UniRef90_R6VGE1 Cluster: Phosphate acyltransferase 0.20 0.0873 4.0E-02 2.9E-01 0.2209 2.6E-02 0.0040 8.7E-01 0.0420 6.2E-01 0.0176 7.4E-01 Alistipes_shahii UniRef90_D4IKW7 Cluster: Peroxiredoxin 0.15 0.0802 4.0E-02 2.9E-01 -0.0182 8.4E-01 -0.0091 6.9E-01 0.1059 1.5E-01 -0.0206 6.8E-01 Alistipes_shahii UniRef90_D4IPR2 Cluster: Phosphoglucomutase 0.23 0.0901 4.1E-02 2.9E-01 0.0974 3.5E-01 -0.0103 6.9E-01 0.1485 8.3E-02 -0.0011 9.8E-01 Alistipes_shahii UniRef90_I3YKF3 Cluster: 30S ribosomal protein S20 0.10 0.0846 4.3E-02 2.9E-01 0.1842 4.6E-02 0.0123 6.2E-01 0.1291 9.9E-02 -0.0007 9.9E-01 Alistipes_shahii UniRef90_D4IQ39 Cluster: Sigma-24 0.11 0.0406 4.5E-02 3.0E-01 -0.0082 8.5E-01 -0.0138 2.4E-01 -0.0067 8.6E-01 -0.0405 1.1E-01 Alistipes_shahii UniRef90_D4IQ85 Cluster: Uncharacterized oxidoreductases, Fe-dependent alcohol 0.20 0.0937 4.5E-02 3.0E-01 0.0350 7.5E-01 0.0119 6.6E-01 0.0664 4.6E-01 -0.0437 4.5E-01 dehydrogenase family Alistipes_shahii UniRef90_D4IJG9 Cluster: Large-conductance mechanosensitive channel 0.12 0.0645 4.5E-02 3.0E-01 0.1239 8.5E-02 -0.0295 1.2E-01 0.0969 1.1E-01 0.0096 8.1E-01 Alistipes_shahii UniRef90_R7JJ11 Cluster: 30S ribosomal protein S17 0.16 0.0934 4.5E-02 3.0E-01 -0.0429 6.9E-01 -0.0094 7.3E-01 0.0568 5.2E-01 0.0046 9.4E-01 Alistipes_shahii UniRef90_D4ILP3 Cluster: Thiamine-monophosphate kinase 0.12 0.0511 4.6E-02 3.0E-01 0.0594 3.0E-01 0.0188 2.1E-01 0.0662 1.8E-01 0.0165 6.1E-01 Alistipes_shahii UniRef90_I3YM41 Cluster: 30S ribosomal protein S13 0.19 0.1196 4.9E-02 3.1E-01 0.1310 3.4E-01 -0.0019 9.6E-01 0.1355 2.4E-01 0.0077 9.2E-01 Alistipes_shahii UniRef90_I3YND9 Cluster: ATP-dependent 6-phosphofructokinase 0.15 0.0569 5.0E-02 3.2E-01 0.0755 2.5E-01 0.0154 3.6E-01 0.0279 6.1E-01 -0.0077 8.3E-01 Alistipes_shahii UniRef90_D4IJD3 Cluster: Acetyl-CoA carboxylase, carboxyltransferase component (Subunits 0.24 0.0868 5.1E-02 3.2E-01 -0.1154 2.7E-01 -0.0383 1.5E-01 0.0588 5.0E-01 0.0012 9.8E-01 alpha and beta) Alistipes_shahii UniRef90_D4IQ54 Cluster: Phosphatidylserine decarboxylase proenzyme 0.11 0.0450 5.2E-02 3.2E-01 0.0266 6.0E-01 0.0131 3.3E-01 0.0257 5.5E-01 0.0599 3.9E-02 Alistipes_shahii UniRef90_D4IL40 Cluster: Glutamine--tRNA ligase 0.16 0.0421 5.3E-02 3.2E-01 0.0322 5.1E-01 -0.0169 1.9E-01 0.0093 8.2E-01 -0.0114 6.8E-01 Alistipes_shahii UniRef90_D4IJJ4 Cluster: Imidazolonepropionase 0.17 0.0688 5.5E-02 3.3E-01 0.0580 4.9E-01 -0.0022 9.2E-01 0.0328 6.4E-01 0.0028 9.5E-01 Alistipes_shahii UniRef90_R6VJD8 Cluster: ATP-dependent Clp protease proteolytic subunit 0.15 0.0589 5.7E-02 3.3E-01 0.0385 5.8E-01 -0.0254 1.6E-01 0.0169 7.7E-01 -0.0446 2.5E-01 Alistipes_shahii UniRef90_I3YNT8 Cluster: DNA-binding protein HU 0.17 0.1117 5.7E-02 3.3E-01 0.0413 7.6E-01 -0.0452 1.9E-01 0.0372 7.5E-01 -0.0849 2.6E-01 Alistipes_shahii UniRef90_D4IPA7 Cluster: Long-chain acyl-CoA synthetases (AMP-forming) 0.16 0.0431 5.7E-02 3.3E-01 -0.0029 9.6E-01 -0.0028 8.3E-01 0.0247 5.7E-01 -0.0029 9.2E-01 Alistipes_shahii UniRef90_D4IQR7 Cluster: Acetyltransferases, including N-acetylases of ribosomal proteins 0.11 0.0642 5.9E-02 3.3E-01 0.0262 7.3E-01 0.0168 3.9E-01 0.0406 5.3E-01 -0.0772 6.8E-02 Alistipes_shahii UniRef90_D4IPN3 Cluster: PKD domain-containing protein 0.12 0.0292 6.0E-02 3.3E-01 0.0598 7.8E-02 0.0094 3.1E-01 0.0362 2.1E-01 0.0153 4.4E-01 Alistipes_shahii UniRef90_D4IMD6 Cluster: UDP-N-acetylmuramate--L-alanine ligase 0.12 0.0282 6.0E-02 3.4E-01 -0.0443 1.9E-01 -0.0078 3.7E-01 0.0658 1.8E-02 -0.0248 1.9E-01 Alistipes_shahii UniRef90_D4IKY9 Cluster: tRNA (guanosine(18)-2'-O)-methyltransferase 0.13 0.0580 6.0E-02 3.3E-01 0.0593 3.9E-01 0.0150 4.0E-01 0.1208 3.9E-02 0.0164 6.7E-01 Alistipes_shahii UniRef90_D4IPB7 Cluster: Acetyltransferase (Isoleucine patch superfamily) 0.12 0.0708 6.1E-02 3.3E-01 0.0040 9.6E-01 -0.0345 1.2E-01 -0.0451 5.3E-01 -0.0472 3.2E-01 Alistipes_shahii UniRef90_D4ILK1 Cluster: Deoxynucleoside kinases 0.15 0.0524 6.1E-02 3.3E-01 0.0822 1.9E-01 0.0078 6.4E-01 0.0046 9.3E-01 -0.0315 3.8E-01 Alistipes_shahii UniRef90_R6VHM7 Cluster: 50S ribosomal protein L31 0.14 0.0713 6.2E-02 3.4E-01 0.0377 6.6E-01 -0.0067 7.7E-01 0.0309 6.6E-01 -0.0356 4.6E-01 Alistipes_shahii UniRef90_D4ILV7 Cluster: 4-hydroxy-3-methylbut-2-enyl diphosphate reductase 0.11 0.0417 6.3E-02 3.4E-01 0.0900 7.0E-02 -0.0014 9.2E-01 0.0481 2.5E-01 0.0119 6.8E-01 Alistipes_shahii UniRef90_D4IJN5 Cluster: Inositol-1-monophosphatase 0.17 0.0725 6.4E-02 3.3E-01 0.0084 9.2E-01 0.0272 2.3E-01 0.0340 6.4E-01 -0.0513 3.0E-01 Alistipes_shahii UniRef90_D4INP2 Cluster: Pirin-related protein 0.14 0.0637 6.4E-02 3.4E-01 0.0072 9.3E-01 -0.0373 6.0E-02 0.0116 8.6E-01 -0.0091 8.3E-01 Alistipes_shahii UniRef90_D4ILQ4 Cluster: Response regulators consisting of a CheY-like receiver domain and 0.15 0.0649 6.6E-02 3.4E-01 0.0977 2.1E-01 0.0307 1.3E-01 0.0869 1.9E-01 0.0064 8.8E-01 a winged-helix DNA-binding domain Alistipes_shahii UniRef90_D4IJ11 Cluster: Outer membrane protein 0.15 0.0726 6.6E-02 3.4E-01 -0.0215 8.1E-01 -0.0300 2.1E-01 0.1379 7.2E-02 -0.1165 2.4E-02 Alistipes_shahii UniRef90_I3YQ80 Cluster: Acyl-CoA dehydrogenase, C-terminal domain protein 0.20 0.0560 6.7E-02 3.4E-01 0.0580 4.0E-01 -0.0170 3.4E-01 0.0474 4.2E-01 0.0263 4.9E-01 Alistipes_shahii UniRef90_D4IMY0 Cluster: Glycosidase 0.13 0.0399 6.7E-02 3.4E-01 0.0281 5.7E-01 0.0190 1.4E-01 -0.0190 6.5E-01 0.0020 9.4E-01 Alistipes_shahii UniRef90_R7DFZ4 Cluster: Gluconate 5-dehydrogenase 0.21 0.1026 6.7E-02 3.4E-01 0.1777 1.7E-01 -0.0365 2.6E-01 0.1019 3.5E-01 -0.0836 2.3E-01 Alistipes_shahii UniRef90_I3YM43 Cluster: 30S ribosomal protein S4 0.21 0.1005 6.9E-02 3.4E-01 -0.0142 9.1E-01 -0.0181 5.8E-01 -0.0450 6.8E-01 -0.0445 5.2E-01 Alistipes_shahii UniRef90_D4IME6 Cluster: Aminopeptidase 0.14 0.0508 7.0E-02 3.4E-01 0.0864 1.7E-01 -0.0013 9.4E-01 0.0576 2.7E-01 -0.0559 1.1E-01 46

Supplementary Data 3b UniRef90 Family Plasma TMAO Red meat Red meat Choline Choline Species Cluster Name Detection member ID Rate Effect P FDR Effect P Effect P Effect P Effect P Alistipes_shahii UniRef90_D4IM12 Cluster: Sialyltransferase PMO188 0.14 0.0487 7.0E-02 3.4E-01 0.0428 4.9E-01 -0.0145 3.5E-01 0.0825 1.1E-01 -0.0787 1.8E-02 Alistipes_shahii UniRef90_I3YKQ4 Cluster: 7-keto-8-aminopelargonate synthetase and related enzymes 0.21 0.0725 7.2E-02 3.5E-01 0.0372 6.9E-01 -0.0161 4.9E-01 -0.0006 9.9E-01 -0.0153 7.6E-01 Alistipes_shahii UniRef90_D4IPB2 Cluster: Putative efflux protein, MATE family 0.14 0.0397 7.3E-02 3.5E-01 0.0985 4.7E-02 -0.0160 2.2E-01 0.0754 7.1E-02 -0.0183 5.1E-01 Alistipes_shahii UniRef90_D4IKV0 Cluster: Amino acid carrier protein 0.15 0.0523 7.3E-02 3.5E-01 -0.0368 5.8E-01 -0.0124 4.7E-01 0.0064 9.1E-01 0.0328 3.7E-01 Alistipes_shahii UniRef90_I3YM13 Cluster: 30S ribosomal protein S7 0.21 0.0891 7.4E-02 3.5E-01 -0.0162 8.9E-01 -0.0014 9.6E-01 0.1141 2.3E-01 0.0064 9.2E-01 Alistipes_shahii UniRef90_R6Y8P0 Cluster: Adenosylhomocysteinase 0.13 0.0369 7.4E-02 3.5E-01 0.0505 2.8E-01 -0.0063 6.1E-01 -0.0248 5.3E-01 -0.0221 4.0E-01 Alistipes_shahii UniRef90_R5V2B2 Cluster: Anaerobic ribonucleoside-triphosphate reductase 0.13 0.0382 7.8E-02 3.6E-01 -0.0098 8.4E-01 0.0045 7.2E-01 0.0065 8.7E-01 0.0125 6.5E-01 Alistipes_shahii UniRef90_D4IPI3 Cluster: Pyridine nucleotide-disulphide oxidoreductase 0.15 0.0475 7.9E-02 3.6E-01 0.0540 3.7E-01 -0.0112 4.9E-01 0.0133 7.9E-01 -0.0158 6.5E-01 Alistipes_shahii UniRef90_D4IMC1 Cluster: Zn-dependent hydrolases, including glyoxylases 0.13 0.0473 8.3E-02 3.7E-01 -0.0330 6.0E-01 0.0083 6.1E-01 0.0496 3.5E-01 -0.0084 8.1E-01 Alistipes_shahii UniRef90_D4IJ34 Cluster: NTP_transferase domain-containing protein 0.18 0.0688 8.3E-02 3.7E-01 0.1684 6.5E-02 -0.0114 6.2E-01 0.1346 7.6E-02 -0.0340 5.0E-01 Alistipes_shahii UniRef90_D4IJD8 Cluster: 2,3-bisphosphoglycerate-independent phosphoglycerate mutase 0.16 0.0402 8.4E-02 3.7E-01 0.0413 4.3E-01 -0.0114 4.1E-01 0.0277 5.3E-01 0.0183 5.4E-01 Alistipes_shahii UniRef90_R6VLN4 Cluster: Na(+)-translocating NADH-quinone reductase subunit D 0.14 0.0486 8.5E-02 3.7E-01 -0.0414 5.1E-01 -0.0022 8.9E-01 0.0317 5.5E-01 -0.0174 6.4E-01 Alistipes_shahii UniRef90_I3YM19 Cluster: 50S ribosomal protein L2 0.22 0.0812 8.6E-02 3.7E-01 -0.0243 8.3E-01 -0.0461 1.0E-01 -0.0129 8.9E-01 -0.0479 4.3E-01 Alistipes_shahii UniRef90_D4INU6 Cluster: NAGPA domain-containing protein 0.19 0.0834 8.6E-02 3.7E-01 0.0762 5.0E-01 0.0026 9.3E-01 0.0904 3.3E-01 -0.0357 5.5E-01 Alistipes_shahii UniRef90_D4IPM4 Cluster: Acetyltransferase (GNAT) family 0.12 0.0446 8.9E-02 3.7E-01 0.0954 1.0E-01 -0.0012 9.4E-01 0.0549 2.7E-01 -0.0269 4.3E-01 Alistipes_shahii UniRef90_D4IPZ9 Cluster: Uncharacterized conserved protein 0.14 0.0939 9.0E-02 3.8E-01 -0.0568 6.5E-01 -0.0216 5.1E-01 0.0791 4.5E-01 -0.0043 9.5E-01 Alistipes_shahii UniRef90_D4IKA7 Cluster: Glucosamine-6-phosphate deaminase 0.19 0.0747 9.2E-02 3.8E-01 0.0035 9.7E-01 -0.0206 4.2E-01 0.0307 7.2E-01 -0.0006 9.9E-01 Alistipes_shahii UniRef90_D4ILF8 Cluster: UPF0597 protein AL1_13010 0.16 0.0563 9.2E-02 3.8E-01 0.0782 3.1E-01 0.0012 9.5E-01 0.1138 7.5E-02 0.0278 5.1E-01 Alistipes_shahii UniRef90_I3YM14 Cluster: Elongation factor G 0.25 0.0865 9.3E-02 3.8E-01 0.1325 2.7E-01 -0.0321 2.8E-01 0.1218 2.2E-01 -0.0540 4.0E-01 Alistipes_shahii UniRef90_I3YKF8 Cluster: 30S ribosomal protein S6 0.14 0.0612 9.4E-02 3.8E-01 0.0157 8.5E-01 -0.0096 6.6E-01 -0.0531 4.4E-01 -0.0408 3.9E-01 Alistipes_shahii UniRef90_R7JJ57 Cluster: Saccharopine dehydrogenase 0.17 0.0477 9.5E-02 3.9E-01 0.0822 2.1E-01 -0.0280 9.7E-02 0.0893 1.0E-01 -0.0371 3.1E-01 Alistipes_shahii UniRef90_D4IMH7 Cluster: N-acetyl-gamma-glutamyl-phosphate reductase 0.12 0.0414 9.5E-02 3.9E-01 0.0236 6.8E-01 0.0116 4.3E-01 0.0298 5.3E-01 -0.0096 7.6E-01 Alistipes_shahii UniRef90_D4IIS1 Cluster: RND family efflux transporter, MFP subunit 0.18 0.0779 9.6E-02 3.9E-01 0.1121 2.9E-01 0.0233 3.9E-01 0.2286 7.9E-03 -0.0318 5.9E-01 Alistipes_shahii UniRef90_I3YKR1 Cluster: Uridylate kinase 0.18 0.0656 9.7E-02 3.9E-01 0.0824 3.6E-01 0.0015 9.5E-01 0.0892 2.4E-01 -0.0490 3.3E-01 Alistipes_shahii UniRef90_D4INE0 Cluster: Cell division protein ZapA 0.14 0.0703 9.7E-02 3.9E-01 0.0683 4.8E-01 -0.0024 9.2E-01 -0.0024 9.8E-01 -0.0379 4.7E-01 Alistipes_shahii UniRef90_D4IN94 Cluster: 4-diphosphocytidyl-2-C-methyl-D-erythritol kinase 0.15 0.0644 9.7E-02 3.9E-01 0.0316 7.2E-01 0.0194 3.9E-01 0.0758 3.1E-01 -0.0272 5.7E-01 Alistipes_shahii UniRef90_D4IJL2 Cluster: FOG: WD40-like repeat 0.17 0.0564 9.9E-02 3.9E-01 0.0238 7.6E-01 0.0012 9.5E-01 0.1134 8.2E-02 -0.0230 6.0E-01 Alistipes_shahii UniRef90_D4IK19 Cluster: Predicted permeases 0.12 0.0318 1.0E-01 3.9E-01 0.0665 1.2E-01 -0.0179 1.1E-01 -0.0296 4.2E-01 -0.0102 6.8E-01 Alistipes_shahii UniRef90_D4IP80 Cluster: FKBP-type peptidyl-prolyl cis-trans isomerase (Trigger factor) 0.18 0.0464 1.0E-01 3.9E-01 0.0935 1.4E-01 -0.0070 6.8E-01 0.0742 1.7E-01 -0.0276 4.4E-01 Alistipes_shahii UniRef90_D4IMF1 Cluster: tRNA pseudouridine synthase B 0.14 0.0426 1.0E-01 3.9E-01 0.0102 8.6E-01 0.0047 7.6E-01 0.0559 2.6E-01 0.0283 4.0E-01 Alistipes_shahii UniRef90_D4IJ91 Cluster: NAD-dependent protein deacetylases, SIR2 family 0.15 0.0705 1.0E-01 4.0E-01 0.0126 9.0E-01 0.0104 6.8E-01 0.0820 3.2E-01 -0.0349 5.3E-01 Alistipes_shahii UniRef90_D4IL67 Cluster: Triosephosphate isomerase (TIM) 0.13 0.0418 1.0E-01 4.0E-01 0.0906 1.2E-01 -0.0227 1.3E-01 0.0118 8.1E-01 -0.0499 1.2E-01 Alistipes_shahii UniRef90_D4IQC1 Cluster: Predicted soluble lytic transglycosylase fused to an ABC-type amino 0.12 0.0417 1.0E-01 4.0E-01 0.1285 2.4E-02 -0.0121 4.3E-01 -0.0115 8.1E-01 -0.0221 5.0E-01 acid-binding protein Alistipes_shahii UniRef90_D4IMC5 Cluster: Uncharacterized conserved protein 0.20 0.0990 1.0E-01 4.0E-01 -0.0501 7.2E-01 -0.0134 7.0E-01 -0.0126 9.1E-01 -0.1758 1.8E-02 Alistipes_shahii UniRef90_D4IKU2 Cluster: Chorismate mutase 0.10 0.0306 1.1E-01 4.0E-01 0.0903 3.0E-02 0.0028 8.0E-01 0.0116 7.4E-01 -0.0046 8.5E-01 Alistipes_shahii UniRef90_D4IMK6 Cluster: 30S ribosomal protein S8 0.14 0.0759 1.1E-01 4.1E-01 0.0977 3.6E-01 0.0097 7.2E-01 0.0736 4.1E-01 -0.0822 1.7E-01 Alistipes_shahii UniRef90_I3YNQ4 Cluster: Asparagine--tRNA ligase 0.20 0.0559 1.1E-01 4.1E-01 0.0800 3.1E-01 -0.0251 2.1E-01 0.0388 5.6E-01 -0.0228 6.0E-01 Alistipes_shahii UniRef90_D4IJZ8 Cluster: Predicted oxidoreductases of the aldo/keto reductase family 0.13 -0.0642 1.1E-01 4.1E-01 -0.0476 6.1E-01 -0.0165 4.7E-01 0.1260 9.8E-02 -0.0179 7.1E-01 Alistipes_shahii UniRef90_D4IPV8 Cluster: Predicted flavoproteins 0.11 0.0350 1.1E-01 4.1E-01 0.0673 1.7E-01 0.0138 2.7E-01 0.0817 4.7E-02 -0.0058 8.3E-01 Alistipes_shahii UniRef90_D4ING3 Cluster: Isoprenyl transferase 0.17 0.0600 1.1E-01 4.0E-01 0.0274 7.5E-01 0.0087 7.0E-01 0.1138 1.2E-01 -0.0355 4.6E-01 Alistipes_shahii UniRef90_D4INE5 Cluster: WG repeat-containing protein 0.13 0.0529 1.1E-01 4.0E-01 0.0475 5.2E-01 -0.0156 4.2E-01 0.0306 6.2E-01 -0.0272 5.1E-01 Alistipes_shahii UniRef90_D4ILF6 Cluster: Nitroreductase family 0.17 0.0863 1.1E-01 4.0E-01 -0.0827 5.1E-01 -0.0212 4.9E-01 -0.0089 9.3E-01 -0.0493 4.6E-01 Alistipes_shahii UniRef90_D4INH6 Cluster: Malate dehydrogenase (NAD) 0.18 0.0543 1.1E-01 4.0E-01 0.0259 7.4E-01 -0.0306 1.2E-01 0.0988 1.3E-01 -0.0450 2.9E-01 Alistipes_shahii UniRef90_I3YQX1 Cluster: NADH peroxidase 0.21 0.1003 1.1E-01 4.0E-01 0.2170 1.4E-01 -0.0221 5.5E-01 0.1444 2.3E-01 -0.0518 5.1E-01 Alistipes_shahii UniRef90_D4IQD3 Cluster: Glutamate dehydrogenase 0.14 0.0391 1.1E-01 4.0E-01 0.0565 3.1E-01 -0.0080 5.8E-01 0.0138 7.7E-01 0.0037 9.0E-01 Alistipes_shahii UniRef90_I3YM20 Cluster: 30S ribosomal protein S19 0.13 0.0621 1.1E-01 4.0E-01 0.1469 8.7E-02 -0.0288 2.1E-01 0.0413 5.8E-01 -0.0078 8.7E-01 Alistipes_shahii UniRef90_R6VF69 Cluster: Exonuclease RecJ 0.22 0.0651 1.1E-01 4.0E-01 0.1735 6.7E-02 -0.0011 9.6E-01 0.1324 9.1E-02 0.0192 7.1E-01 Alistipes_shahii UniRef90_D4IMM3 Cluster: acidPPc domain-containing protein 0.13 0.0536 1.1E-01 4.0E-01 0.0314 6.8E-01 0.0257 1.9E-01 0.0360 5.8E-01 -0.0205 6.3E-01 Alistipes_shahii UniRef90_I3YLX2 Cluster: 50S ribosomal protein L19 0.19 0.0816 1.1E-01 4.0E-01 0.1580 1.7E-01 -0.0362 2.3E-01 0.1014 3.0E-01 0.0330 6.1E-01 Alistipes_shahii UniRef90_D4IP67 Cluster: tRNA(Ile)-lysidine synthase 0.13 0.0346 1.1E-01 4.0E-01 0.0588 2.3E-01 -0.0087 5.0E-01 -0.0079 8.5E-01 0.0122 6.6E-01 Alistipes_shahii UniRef90_I3YNJ2 Cluster: Undecaprenyl-phosphate 4-deoxy-4-formamido-L-arabinose 0.14 0.0551 1.1E-01 4.0E-01 0.0858 2.7E-01 -0.0112 5.8E-01 0.1230 6.3E-02 -0.0643 1.4E-01 transferase Alistipes_shahii UniRef90_I3YJ24 Cluster: 50S ribosomal protein L32 0.12 0.0805 1.1E-01 4.0E-01 0.0053 9.6E-01 -0.0343 2.5E-01 -0.0878 3.5E-01 0.0059 9.3E-01 Alistipes_shahii UniRef90_D4IN31 Cluster: 3-dehydroquinate synthase 0.11 0.0396 1.1E-01 4.0E-01 0.0802 1.5E-01 0.0135 3.6E-01 0.0140 7.7E-01 -0.0471 1.4E-01 Alistipes_shahii UniRef90_D4INE4 Cluster: Glutamate dehydrogenase 0.25 0.0894 1.1E-01 4.0E-01 -0.0489 7.2E-01 -0.0352 2.8E-01 -0.0620 5.7E-01 -0.0440 5.3E-01 Alistipes_shahii UniRef90_D4INP4 Cluster: L-aspartate oxidase 0.14 0.0319 1.2E-01 4.1E-01 0.0336 4.7E-01 -0.0137 2.5E-01 0.0434 2.7E-01 -0.0204 4.2E-01 Alistipes_shahii UniRef90_D4IPU6 Cluster: 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase 0.17 0.0871 1.2E-01 4.1E-01 0.0769 5.4E-01 -0.0256 4.3E-01 0.0684 5.2E-01 -0.0848 2.2E-01 Alistipes_shahii UniRef90_D4IM06 Cluster: UDP-N-acetylmuramoyl-L-alanyl-D-glutamate--2,6- 0.11 0.0248 1.2E-01 4.1E-01 0.0093 7.9E-01 -0.0033 7.3E-01 -0.0016 9.6E-01 -0.0279 1.7E-01 diaminopimelate ligase Alistipes_shahii UniRef90_D4IMX3 Cluster: Endo-beta-N-acetylglucosaminidase H 0.15 0.1027 1.2E-01 4.1E-01 0.0960 5.4E-01 0.0032 9.3E-01 0.0282 8.2E-01 0.0140 8.6E-01 Alistipes_shahii UniRef90_D4IMM0 Cluster: Triosephosphate isomerase 0.20 0.0687 1.2E-01 4.1E-01 0.0390 7.1E-01 -0.0244 3.4E-01 -0.0122 8.9E-01 -0.0078 8.9E-01 Alistipes_shahii UniRef90_I3YMC4 Cluster: Alpha-L-fucosidase 0.10 0.0194 1.2E-01 4.1E-01 0.0349 2.1E-01 0.0067 3.6E-01 0.0385 9.9E-02 -0.0135 3.9E-01 Alistipes_shahii UniRef90_D4IJJ9 Cluster: Bifunctional PLP-dependent enzyme with beta-cystathionase and 0.15 0.0486 1.2E-01 4.1E-01 0.0495 4.8E-01 -0.0027 8.8E-01 0.0227 7.0E-01 0.0064 8.7E-01 maltose regulon repressor activities Alistipes_shahii UniRef90_D4INE2 Cluster: Aminomethyltransferase 0.15 0.0473 1.2E-01 4.1E-01 0.0518 4.5E-01 0.0061 7.3E-01 0.0472 4.1E-01 -0.0101 7.9E-01 Alistipes_shahii UniRef90_D4IQ60 Cluster: Chloride channel protein EriC 0.14 -0.0319 1.2E-01 4.1E-01 -0.0362 4.4E-01 -0.0049 6.9E-01 -0.0120 7.6E-01 -0.0111 6.7E-01 Alistipes_shahii UniRef90_D4IMK7 Cluster: 50S ribosomal protein L18 0.16 0.0839 1.2E-01 4.1E-01 0.1745 1.6E-01 0.0232 4.7E-01 0.0778 4.6E-01 -0.0112 8.7E-01 Alistipes_shahii UniRef90_D4ILZ9 Cluster: 50S ribosomal protein L25 0.17 0.0578 1.2E-01 4.1E-01 0.1091 2.1E-01 0.0072 7.4E-01 0.0178 8.0E-01 -0.0360 4.5E-01 Alistipes_shahii UniRef90_I3YHW0 Cluster: ATP-dependent DNA helicase RecQ 0.23 0.0583 1.3E-01 4.1E-01 0.0148 8.7E-01 -0.0499 2.4E-02 0.0534 4.7E-01 -0.0511 2.8E-01 Alistipes_shahii UniRef90_D4IJK1 Cluster: RND family efflux transporter, MFP subunit 0.18 0.0850 1.3E-01 4.2E-01 -0.0779 5.5E-01 -0.0068 8.3E-01 0.0529 6.2E-01 -0.0641 3.5E-01 Alistipes_shahii UniRef90_D4IND8 Cluster: Ribosomal protein S12 methylthiotransferase RimO 0.17 0.0492 1.3E-01 4.2E-01 0.0846 2.5E-01 -0.0243 1.9E-01 0.0253 6.8E-01 -0.0252 5.3E-01 Alistipes_shahii UniRef90_R6VHZ6 Cluster: Multifunctional fusion protein 0.16 0.0415 1.3E-01 4.2E-01 0.0408 5.1E-01 -0.0122 4.5E-01 0.0479 3.6E-01 0.0306 3.8E-01 Alistipes_shahii UniRef90_D4IJT7 Cluster: Transcriptional regulator, AraC family 0.10 0.0402 1.3E-01 4.2E-01 0.0006 9.9E-01 -0.0214 1.7E-01 0.1044 3.3E-02 0.0299 3.7E-01 Alistipes_shahii UniRef90_D4ILH6 Cluster: tRNA-specific 2-thiouridylase MnmA 0.15 0.0397 1.3E-01 4.2E-01 0.0277 6.5E-01 -0.0065 6.8E-01 0.0935 6.7E-02 -0.0226 5.1E-01 Alistipes_shahii UniRef90_D4IP32 Cluster: Predicted permease 0.11 0.0234 1.3E-01 4.2E-01 -0.0273 4.5E-01 -0.0196 3.5E-02 -0.0111 7.1E-01 0.0143 4.8E-01 Alistipes_shahii UniRef90_I3YNM3 Cluster: Orotidine 5'-phosphate decarboxylase 0.14 0.0405 1.4E-01 4.3E-01 -0.0551 3.7E-01 -0.0183 2.5E-01 -0.0328 5.2E-01 0.0020 9.5E-01 Alistipes_shahii UniRef90_D4IJ62 Cluster: Pseudouridine synthase 0.14 0.0413 1.4E-01 4.3E-01 0.0147 8.1E-01 -0.0150 3.7E-01 0.0505 3.3E-01 -0.0012 9.7E-01 Alistipes_shahii UniRef90_D4ILK4 Cluster: zf-RING_7 domain-containing protein 0.20 0.0667 1.4E-01 4.3E-01 0.1199 2.5E-01 -0.0083 7.5E-01 0.0763 3.8E-01 0.0512 3.5E-01 Alistipes_shahii UniRef90_D4INX9 Cluster: Glyceraldehyde-3-phosphate dehydrogenase 0.25 0.0920 1.4E-01 4.3E-01 0.0909 5.3E-01 -0.0112 7.5E-01 0.0317 7.9E-01 -0.0098 9.0E-01 Alistipes_shahii UniRef90_I3YLZ7 Cluster: N-acetyltransferase domain-containing protein 0.10 0.0267 1.4E-01 4.3E-01 0.0808 3.9E-02 0.0059 5.8E-01 0.0479 1.5E-01 -0.0157 4.9E-01 Alistipes_shahii UniRef90_D4IPU3 Cluster: 3-isopropylmalate dehydratase large subunit 0.17 0.0492 1.4E-01 4.3E-01 0.1857 1.3E-02 0.0125 5.1E-01 0.0595 3.4E-01 -0.0289 4.8E-01 Alistipes_shahii UniRef90_D4ILQ3 Cluster: Glutamate 5-kinase 0.19 0.0749 1.4E-01 4.3E-01 0.1409 2.3E-01 0.0119 6.8E-01 0.1013 2.9E-01 -0.1489 1.7E-02 Alistipes_shahii UniRef90_D4IPQ4 Cluster: Signal peptidase I 0.17 0.0391 1.4E-01 4.3E-01 0.0385 5.2E-01 0.0020 9.0E-01 0.0214 6.7E-01 -0.0095 7.7E-01 Alistipes_shahii UniRef90_D4IM97 Cluster: Glycoside hydrolase 97 0.17 0.0356 1.4E-01 4.3E-01 0.0264 6.4E-01 0.0044 7.6E-01 0.0556 2.4E-01 0.0310 3.2E-01 Alistipes_shahii UniRef90_D4IJR0 Cluster: Predicted phosphohydrolases 0.12 0.0323 1.4E-01 4.3E-01 0.0515 3.0E-01 0.0098 4.4E-01 0.0094 8.2E-01 -0.0168 5.4E-01 Alistipes_shahii UniRef90_I3YIB7 Cluster: Nucleoside transporter 0.15 0.0390 1.4E-01 4.3E-01 0.0157 7.9E-01 -0.0070 6.6E-01 0.0471 3.5E-01 -0.0184 5.9E-01 Alistipes_shahii UniRef90_I3YLE0 Cluster: 2-amino-3-ketobutyrate coenzyme A ligase 0.19 0.0601 1.4E-01 4.3E-01 0.1322 1.6E-01 -0.0330 1.6E-01 0.0455 5.6E-01 -0.0546 2.8E-01 Alistipes_shahii UniRef90_D4IJJ1 Cluster: Glutamate formiminotransferase 0.18 0.0605 1.4E-01 4.3E-01 0.1438 1.3E-01 0.0098 6.8E-01 0.0665 4.0E-01 -0.0278 5.9E-01 Alistipes_shahii UniRef90_D4IM68 Cluster: Ribonuclease HII 0.13 0.0529 1.4E-01 4.3E-01 0.0917 2.6E-01 0.0084 6.9E-01 0.0864 2.1E-01 -0.0351 4.3E-01 Alistipes_shahii UniRef90_D4IJR5 Cluster: ABC-type multidrug transport system, permease component 0.16 0.0432 1.4E-01 4.3E-01 0.0712 2.8E-01 -0.0163 3.6E-01 0.0384 5.0E-01 -0.0674 7.6E-02 Alistipes_shahii UniRef90_D4IJQ9 Cluster: Small-conductance mechanosensitive channel 0.14 0.0351 1.5E-01 4.3E-01 0.0472 3.8E-01 0.0033 8.1E-01 0.0238 6.0E-01 0.0008 9.8E-01 Alistipes_shahii UniRef90_D4IM62 Cluster: Octanoyltransferase 0.16 0.0439 1.5E-01 4.3E-01 0.0954 1.6E-01 0.0201 2.6E-01 0.1096 5.1E-02 0.0391 3.1E-01 Alistipes_shahii UniRef90_D4IM20 Cluster: Phosphoglycerate kinase 0.18 0.0493 1.5E-01 4.3E-01 -0.0355 6.5E-01 -0.0282 1.6E-01 0.0438 5.0E-01 0.0071 8.7E-01 47

Supplementary Data 3b UniRef90 Family Plasma TMAO Red meat Red meat Choline Choline Species Cluster Name Detection member ID Rate Effect P FDR Effect P Effect P Effect P Effect P Alistipes_shahii UniRef90_I3YMY0 Cluster: Transcription termination/antitermination protein NusG 0.21 0.0742 1.5E-01 4.3E-01 0.0164 8.9E-01 -0.0149 6.2E-01 0.0512 6.0E-01 -0.0124 8.5E-01 Alistipes_shahii UniRef90_D4IKC6 Cluster: Threonine synthase 0.13 0.0396 1.5E-01 4.4E-01 0.1382 2.5E-02 0.0211 1.9E-01 0.0137 7.9E-01 0.0222 5.2E-01 Alistipes_shahii UniRef90_D4ING6 Cluster: Outer membrane protein 0.18 0.0666 1.5E-01 4.4E-01 0.0358 7.3E-01 -0.0226 4.0E-01 0.0451 6.0E-01 -0.0236 6.8E-01 Alistipes_shahii UniRef90_D4IJE4 Cluster: ABC-type multidrug transport system, ATPase and permease 0.12 0.0368 1.5E-01 4.4E-01 0.0434 4.5E-01 -0.0100 5.0E-01 0.0357 4.6E-01 -0.0561 8.0E-02 components Alistipes_shahii UniRef90_I3YIL0 Cluster: H(+)-transporting ATP synthase, vacuolar type, subunit D 0.15 0.0544 1.5E-01 4.4E-01 0.0652 4.5E-01 -0.0071 7.5E-01 0.0794 2.7E-01 0.0075 8.7E-01 Alistipes_shahii UniRef90_D4IPF0 Cluster: Nitroreductase 0.13 0.0372 1.5E-01 4.4E-01 0.0848 1.5E-01 0.0213 1.6E-01 0.0667 1.7E-01 0.0317 3.3E-01 Alistipes_shahii UniRef90_D4IMJ2 Cluster: 30S ribosomal protein S10 0.20 0.0940 1.6E-01 4.4E-01 -0.1442 3.5E-01 -0.0453 2.4E-01 -0.0255 8.4E-01 -0.0082 9.2E-01 Alistipes_shahii UniRef90_D4IM59 Cluster: Nitroreductase 0.10 0.0414 1.6E-01 4.4E-01 -0.0092 8.9E-01 -0.0174 3.1E-01 0.0184 7.4E-01 -0.0473 2.0E-01 Alistipes_shahii UniRef90_D4ILK9 Cluster: Ion-translocating oxidoreductase complex subunit G 0.13 0.0515 1.6E-01 4.5E-01 0.0235 7.7E-01 0.0048 8.2E-01 -0.0114 8.7E-01 0.0137 7.7E-01 Alistipes_shahii UniRef90_I3YQL2 Cluster: DNA gyrase subunit B 0.24 0.0768 1.6E-01 4.5E-01 0.0401 7.5E-01 -0.0225 4.7E-01 0.0277 7.9E-01 0.0085 9.0E-01 Alistipes_shahii UniRef90_R7JHI3 Cluster: Acyl carrier protein 0.17 0.0985 1.6E-01 4.5E-01 -0.0964 5.4E-01 -0.0040 9.2E-01 0.1195 3.7E-01 -0.0791 3.7E-01 Alistipes_shahii UniRef90_I3YHG2 Cluster: Protein RecA 0.22 0.0736 1.6E-01 4.5E-01 0.1163 3.4E-01 -0.0032 9.2E-01 0.2285 2.2E-02 -0.0589 3.6E-01 Alistipes_shahii UniRef90_D4IKC0 Cluster: Transcriptional regulator/sugar kinase 0.13 0.0352 1.6E-01 4.4E-01 0.0552 3.4E-01 -0.0001 9.9E-01 0.0121 8.0E-01 -0.0183 5.7E-01 Alistipes_shahii UniRef90_D4ILJ7 Cluster: 3'(2'),5'-bisphosphate nucleotidase CysQ 0.17 0.0528 1.6E-01 4.4E-01 0.1827 2.7E-02 -0.0013 9.5E-01 0.0771 2.7E-01 0.0120 8.0E-01 Alistipes_shahii UniRef90_R6VSH9 Cluster: Arginine--tRNA ligase 0.16 0.0296 1.6E-01 4.4E-01 0.1064 2.1E-02 0.0155 2.0E-01 0.0552 1.6E-01 0.0143 5.9E-01 Alistipes_shahii UniRef90_D4ILW7 Cluster: Protein TonB 0.26 0.0981 1.6E-01 4.4E-01 -0.0639 7.0E-01 -0.0705 7.6E-02 0.0199 8.8E-01 -0.0472 5.8E-01 Alistipes_shahii UniRef90_I3YQS2 Cluster: Beta sliding clamp 0.20 0.0642 1.6E-01 4.4E-01 0.1082 3.1E-01 -0.0234 3.7E-01 0.1747 4.9E-02 -0.0452 4.2E-01 Alistipes_shahii UniRef90_D4ILG4 Cluster: Dipeptidase PepE 0.14 0.0510 1.6E-01 4.4E-01 -0.0412 6.2E-01 0.0070 7.4E-01 0.0163 8.1E-01 0.0160 7.3E-01 Alistipes_shahii UniRef90_D4ILP8 Cluster: Probable butyrate kinase 0.14 0.0364 1.6E-01 4.4E-01 0.0250 6.7E-01 0.0096 5.3E-01 0.0263 5.9E-01 0.0244 4.6E-01 Alistipes_shahii UniRef90_D4ING1 Cluster: Pyridoxine 5'-phosphate synthase 0.13 0.0454 1.6E-01 4.4E-01 0.0181 8.0E-01 -0.0055 7.7E-01 0.1231 4.4E-02 0.0305 4.5E-01 Alistipes_shahii UniRef90_R6XPF9 Cluster: L-threonine 3-dehydrogenase 0.16 0.0807 1.6E-01 4.5E-01 -0.1952 1.4E-01 -0.0664 4.4E-02 -0.0346 7.5E-01 -0.1111 1.2E-01 Alistipes_shahii UniRef90_R6WSX0 Cluster: 2-oxoglutarate oxidoreductase subunit KorB 0.19 0.0605 1.6E-01 4.5E-01 -0.0045 9.6E-01 0.0006 9.8E-01 0.0909 2.7E-01 0.0546 3.2E-01 Alistipes_shahii UniRef90_D4ILQ2 Cluster: Gamma-glutamyl phosphate reductase 0.18 0.0619 1.7E-01 4.5E-01 0.0937 3.6E-01 0.0275 2.8E-01 0.2229 8.3E-03 -0.0426 4.4E-01 Alistipes_shahii UniRef90_I3YQX0 Cluster: Energy-dependent translational throttle protein EttA 0.20 0.0437 1.7E-01 4.5E-01 0.0749 3.0E-01 -0.0066 7.2E-01 0.0866 1.5E-01 0.0231 5.6E-01 Alistipes_shahii UniRef90_D4IPC4 Cluster: Subtilisin-like serine proteases 0.16 0.0432 1.7E-01 4.5E-01 0.0489 5.0E-01 -0.0043 8.1E-01 0.0644 2.9E-01 -0.0112 7.8E-01 Alistipes_shahii UniRef90_D4IP37 Cluster: Pyruvate:ferredoxin oxidoreductase and related 2- 0.13 0.0591 1.7E-01 4.5E-01 0.0062 9.5E-01 -0.0222 3.8E-01 -0.0329 6.8E-01 0.0054 9.2E-01 oxoacid:ferredoxin oxidoreductases, gamma subunit Alistipes_shahii UniRef90_D4IQG0 Cluster: Peptidase family S41 0.16 0.0548 1.7E-01 4.5E-01 0.0293 7.5E-01 -0.0382 1.0E-01 -0.0558 4.6E-01 -0.0787 1.2E-01 Alistipes_shahii UniRef90_D4IP78 Cluster: Methylenetetrahydrofolate reductase 0.13 0.0496 1.7E-01 4.5E-01 0.0865 2.9E-01 -0.0163 4.4E-01 0.0883 2.0E-01 -0.0148 7.5E-01 Alistipes_shahii UniRef90_D4IJ50 Cluster: Tetratricopeptide repeat 0.23 0.0737 1.7E-01 4.5E-01 -0.0005 1.0E+00 -0.0467 1.3E-01 0.0396 7.0E-01 -0.1505 2.5E-02 Alistipes_shahii UniRef90_D4IQG8 Cluster: Transcriptional regulators of sugar metabolism 0.22 0.0996 1.7E-01 4.5E-01 -0.0794 6.5E-01 -0.0147 7.2E-01 0.0281 8.4E-01 -0.1557 8.1E-02 Alistipes_shahii UniRef90_D4INE6 Cluster: Glucose-6-phosphate isomerase 0.19 0.0507 1.7E-01 4.5E-01 0.0604 4.7E-01 -0.0152 4.8E-01 0.0658 3.5E-01 -0.0455 3.3E-01 Alistipes_shahii UniRef90_D4ING5 Cluster: Outer membrane protein 0.11 0.0315 1.7E-01 4.5E-01 -0.0063 9.0E-01 -0.0189 1.6E-01 0.0248 5.6E-01 -0.0266 3.5E-01 Alistipes_shahii UniRef90_I3YKT8 Cluster: Arabinose operon regulatory protein 0.11 0.0244 1.8E-01 4.5E-01 0.0430 3.1E-01 -0.0184 7.7E-02 0.0025 9.4E-01 -0.0013 9.5E-01 Alistipes_shahii UniRef90_D4IPG5 Cluster: Subtilisin-like serine proteases 0.20 0.0748 1.8E-01 4.5E-01 -0.0022 9.9E-01 -0.0659 3.9E-02 0.1196 2.6E-01 -0.0855 2.2E-01 Alistipes_shahii UniRef90_D4IJ28 Cluster: Nucleoside-diphosphate-sugar epimerases 0.11 0.0402 1.8E-01 4.5E-01 -0.0951 1.4E-01 -0.0039 8.2E-01 0.0775 1.6E-01 -0.0164 6.6E-01 Alistipes_shahii UniRef90_D4IQQ2 Cluster: Cysteine synthase B 0.12 0.0294 1.8E-01 4.5E-01 0.0690 1.6E-01 0.0067 6.1E-01 0.1145 5.8E-03 -0.0017 9.5E-01 Alistipes_shahii UniRef90_D4IQN6 Cluster: Predicted esterase of the alpha-beta hydrolase superfamily 0.13 0.0379 1.8E-01 4.6E-01 0.0126 8.4E-01 0.0006 9.7E-01 -0.0045 9.3E-01 -0.0395 2.8E-01 Alistipes_shahii UniRef90_D4IKV1 Cluster: Copper-(Or silver)-translocating P-type ATPase 0.14 0.0370 1.8E-01 4.6E-01 0.0469 4.6E-01 0.0086 5.9E-01 0.0812 1.2E-01 -0.0099 7.7E-01 Alistipes_shahii UniRef90_D4IP26 Cluster: ParB-like partition proteins 0.15 0.0380 1.8E-01 4.5E-01 0.0164 8.0E-01 -0.0135 4.2E-01 0.1144 3.3E-02 0.0358 3.2E-01 Alistipes_shahii UniRef90_I3YJY0 Cluster: Glycine cleavage system H protein 0.16 0.0864 1.8E-01 4.5E-01 0.1423 3.4E-01 0.0157 6.7E-01 0.1288 3.0E-01 -0.0006 9.9E-01 Alistipes_shahii UniRef90_D4IMG8 Cluster: Cardiolipin synthase 0.18 0.0378 1.8E-01 4.6E-01 0.0343 6.0E-01 -0.0083 6.1E-01 0.0465 3.8E-01 0.0276 4.4E-01 Alistipes_shahii UniRef90_D4IKW8 Cluster: Ribosome-recycling factor 0.17 0.0574 1.9E-01 4.6E-01 0.0105 9.2E-01 0.0084 7.4E-01 0.0483 5.6E-01 -0.0131 8.1E-01 Alistipes_shahii UniRef90_D4IKY7 Cluster: Probable endonuclease 4 0.17 0.0454 1.9E-01 4.6E-01 0.1232 1.2E-01 -0.0055 7.8E-01 0.0451 4.9E-01 0.0071 8.7E-01 Alistipes_shahii UniRef90_R6VNX6 Cluster: Replicative DNA helicase 0.18 0.0329 1.9E-01 4.6E-01 0.0706 2.1E-01 -0.0001 9.9E-01 0.1247 7.9E-03 -0.0601 5.4E-02 Alistipes_shahii UniRef90_D4IN95 Cluster: GSCFA family 0.12 0.0394 1.9E-01 4.6E-01 0.0039 9.5E-01 0.0012 9.5E-01 0.0278 6.2E-01 -0.0326 3.9E-01 Alistipes_shahii UniRef90_D4IQ38 Cluster: DUF4974 domain-containing protein 0.17 -0.0420 1.9E-01 4.6E-01 -0.0676 3.5E-01 -0.0031 8.6E-01 -0.0119 8.4E-01 -0.0336 3.9E-01 Alistipes_shahii UniRef90_I3YMX8 Cluster: Elongation factor Tu 0.26 0.1000 1.9E-01 4.6E-01 -0.0523 7.8E-01 -0.0609 1.6E-01 0.0124 9.3E-01 -0.0928 3.2E-01 Alistipes_shahii UniRef90_D4IJQ0 Cluster: Shikimate dehydrogenase 0.16 0.0534 1.9E-01 4.6E-01 0.0659 4.8E-01 0.0177 4.5E-01 0.0199 8.0E-01 -0.0014 9.8E-01 Alistipes_shahii UniRef90_D4IJL9 Cluster: Ferrous iron transport protein B 0.12 0.0159 2.0E-01 4.7E-01 0.0065 8.1E-01 -0.0062 3.9E-01 0.0135 5.6E-01 -0.0022 8.9E-01 Alistipes_shahii UniRef90_R6VU97 Cluster: Na(+)-translocating NADH-quinone reductase subunit B 0.15 0.0348 2.0E-01 4.8E-01 -0.0297 6.2E-01 -0.0162 3.1E-01 -0.0265 6.1E-01 -0.0129 7.1E-01 Alistipes_shahii UniRef90_D4IM17 Cluster: Glycerophosphoryl diester phosphodiesterase 0.15 0.0328 2.0E-01 4.8E-01 0.0982 9.8E-02 0.0012 9.4E-01 0.0592 2.3E-01 0.0319 3.3E-01 Alistipes_shahii UniRef90_I3YII8 Cluster: ATP-dependent Clp protease ATP-binding subunit ClpX 0.18 0.0413 2.0E-01 4.8E-01 0.0382 6.0E-01 -0.0021 9.2E-01 0.0198 7.5E-01 -0.0659 1.2E-01 Alistipes_shahii UniRef90_D4IJ45 Cluster: DNA segregation ATPase FtsK/SpoIIIE and related proteins 0.21 0.0453 2.0E-01 4.8E-01 0.1070 1.9E-01 -0.0076 7.1E-01 0.0935 1.6E-01 -0.0331 4.5E-01 Alistipes_shahii UniRef90_D4ILW3 Cluster: Cation diffusion facilitator family transporter 0.16 0.0475 2.0E-01 4.8E-01 -0.0684 4.2E-01 -0.0239 2.7E-01 0.1284 6.6E-02 0.0372 4.3E-01 Alistipes_shahii UniRef90_D4IML9 Cluster: Histidinol phosphatase and related hydrolases of the PHP family 0.16 0.0456 2.0E-01 4.8E-01 0.0492 5.5E-01 -0.0196 3.4E-01 0.0317 6.4E-01 -0.0883 4.6E-02 Alistipes_shahii UniRef90_D4ILW5 Cluster: Phosphoglycerol transferase and related proteins, alkaline 0.17 0.0316 2.0E-01 4.8E-01 0.0924 1.0E-01 0.0114 4.4E-01 0.1001 3.4E-02 -0.0200 5.3E-01 phosphatase superfamily Alistipes_shahii UniRef90_I3YM29 Cluster: 30S ribosomal protein S14 0.15 0.0680 2.0E-01 4.8E-01 0.0878 4.7E-01 0.0391 2.1E-01 0.1290 2.1E-01 0.0362 5.9E-01 Alistipes_shahii UniRef90_D4IL45 Cluster: Inosine-5'-monophosphate dehydrogenase 0.19 0.0388 2.0E-01 4.8E-01 0.0466 5.0E-01 0.0127 4.8E-01 0.0037 9.5E-01 -0.0116 7.6E-01 Alistipes_shahii UniRef90_D4INC6 Cluster: Peptidyl-prolyl cis-trans isomerase 0.11 0.0311 2.0E-01 4.8E-01 0.0541 3.1E-01 0.0150 2.9E-01 0.0679 1.4E-01 0.0155 6.2E-01 Alistipes_shahii UniRef90_D4IQ55 Cluster: Phosphatidate cytidylyltransferase 0.14 0.0430 2.0E-01 4.8E-01 0.0236 7.5E-01 0.0009 9.7E-01 -0.0292 6.5E-01 0.0461 2.8E-01 Alistipes_shahii UniRef90_D4INB3 Cluster: Inositol 2-dehydrogenase 0.20 0.0372 2.1E-01 4.8E-01 0.0982 1.5E-01 -0.0349 4.0E-02 0.0795 1.6E-01 -0.0252 4.9E-01 Alistipes_shahii UniRef90_UPI000366D0E0 Cluster: YitT family protein 0.16 0.0332 2.1E-01 4.8E-01 0.0399 4.9E-01 -0.0169 2.7E-01 -0.0003 1.0E+00 -0.0562 9.1E-02 Alistipes_shahii UniRef90_I3YJY1 Cluster: Malate dehydrogenase 0.25 0.0786 2.1E-01 4.9E-01 0.0745 6.2E-01 -0.0281 4.4E-01 0.0580 6.4E-01 -0.0674 3.9E-01 Alistipes_shahii UniRef90_D4IJI4 Cluster: Glucose-1-phosphate thymidylyltransferase 0.11 0.0284 2.1E-01 4.9E-01 0.0755 1.3E-01 0.0088 5.1E-01 0.0959 2.4E-02 0.0565 5.1E-02 Alistipes_shahii UniRef90_D4IL20 Cluster: Mannonate dehydratase 0.12 0.0340 2.1E-01 4.9E-01 0.0261 6.8E-01 0.0094 5.6E-01 0.0109 8.4E-01 0.0073 8.3E-01 Alistipes_shahii UniRef90_I3YP21 Cluster: Ribosomal silencing factor RsfS 0.12 0.0408 2.1E-01 4.9E-01 0.0668 3.6E-01 -0.0109 5.7E-01 0.0286 6.4E-01 -0.0063 8.8E-01 Alistipes_shahii UniRef90_D4INA7 Cluster: Tetraacyldisaccharide 4'-kinase 0.19 0.0587 2.1E-01 4.9E-01 0.2009 5.7E-02 0.0176 5.2E-01 0.0958 2.8E-01 0.0008 9.9E-01 Alistipes_shahii UniRef90_R7JJN8 Cluster: Translation initiation factor IF-1 0.12 0.0444 2.2E-01 4.9E-01 -0.0072 9.3E-01 0.0006 9.8E-01 0.0100 8.8E-01 -0.1018 2.7E-02 Alistipes_shahii UniRef90_D4IPG3 Cluster: Uncharacterized flavoproteins 0.17 0.0478 2.2E-01 4.9E-01 0.0608 4.9E-01 -0.0270 2.3E-01 0.0247 7.3E-01 0.0051 9.2E-01 Alistipes_shahii UniRef90_D4IQ74 Cluster: Antirepressor regulating drug resistance, predicted signal 0.13 0.0224 2.2E-01 4.9E-01 0.0490 2.3E-01 0.0017 8.7E-01 0.0362 2.9E-01 -0.0060 7.9E-01 transduction N-terminal membrane component Alistipes_shahii UniRef90_D4IN11 Cluster: Predicted metal-dependent hydrolase 0.12 0.0423 2.2E-01 4.9E-01 0.0724 3.4E-01 -0.0191 3.5E-01 -0.0384 5.5E-01 -0.0248 5.7E-01 Alistipes_shahii UniRef90_D4IL66 Cluster: Thymidylate kinase 0.12 0.0360 2.2E-01 4.9E-01 0.0167 8.0E-01 -0.0106 5.3E-01 0.0855 1.2E-01 -0.0002 1.0E+00 Alistipes_shahii UniRef90_I3YHG0 Cluster: Peroxiredoxin 0.16 0.0614 2.2E-01 4.9E-01 0.1940 9.0E-02 -0.0093 7.5E-01 0.0016 9.9E-01 -0.0684 2.7E-01 Alistipes_shahii UniRef90_D4IMH4 Cluster: Acetylglutamate kinase 0.13 0.0395 2.2E-01 4.9E-01 0.0804 2.8E-01 -0.0194 3.1E-01 0.0682 2.8E-01 -0.0292 4.8E-01 Alistipes_shahii UniRef90_D4IK14 Cluster: Membrane-bound serine protease (ClpP class) 0.14 0.0492 2.3E-01 5.0E-01 0.0082 9.3E-01 0.0201 3.9E-01 0.1332 7.8E-02 -0.0071 8.9E-01 Alistipes_shahii UniRef90_D4INI9 Cluster: Poly(3-hydroxybutyrate) depolymerase 0.13 0.0434 2.3E-01 5.0E-01 -0.0459 5.7E-01 -0.0383 6.9E-02 -0.0494 4.5E-01 -0.0122 7.9E-01 Alistipes_shahii UniRef90_D4IJN4 Cluster: Glutamine--fructose-6-phosphate aminotransferase [isomerizing] 0.13 0.0269 2.3E-01 5.0E-01 0.0415 4.1E-01 -0.0126 3.3E-01 -0.0224 6.0E-01 -0.0100 7.2E-01 Alistipes_shahii UniRef90_D4ILI2 Cluster: Release factor glutamine methyltransferase 0.17 0.0582 2.3E-01 5.0E-01 -0.0096 9.3E-01 0.0224 4.2E-01 0.1776 5.0E-02 -0.0704 2.4E-01 Alistipes_shahii UniRef90_I3YPA5 Cluster: Transcriptional regulator/sugar kinase 0.17 0.0402 2.3E-01 5.0E-01 0.1008 1.7E-01 -0.0046 8.1E-01 0.0399 5.3E-01 -0.0430 3.1E-01 Alistipes_shahii UniRef90_D4IK20 Cluster: Methionyl-tRNA formyltransferase 0.15 0.0415 2.3E-01 5.0E-01 0.0155 8.4E-01 -0.0167 4.2E-01 0.0476 4.7E-01 -0.0117 7.9E-01 Alistipes_shahii UniRef90_I3YM95 Cluster: Proline--tRNA ligase 0.20 0.0377 2.3E-01 5.0E-01 0.1177 1.0E-01 -0.0060 7.4E-01 0.0676 2.6E-01 0.0149 7.0E-01 Alistipes_shahii UniRef90_D4IM72 Cluster: Biopolymer transport proteins 0.25 0.0931 2.3E-01 5.0E-01 0.0773 6.8E-01 -0.0265 5.5E-01 0.1826 2.3E-01 -0.0816 3.9E-01 Alistipes_shahii UniRef90_D4IL36 Cluster: Predicted membrane protein 0.15 0.0307 2.3E-01 5.0E-01 0.1742 2.1E-03 -0.0012 9.4E-01 0.0450 3.5E-01 0.0081 8.0E-01 Alistipes_shahii UniRef90_I3YHU9 Cluster: 50S ribosomal protein L21 0.21 0.0693 2.3E-01 5.0E-01 0.0911 4.9E-01 -0.0436 1.9E-01 0.1776 1.1E-01 -0.0965 1.8E-01 Alistipes_shahii UniRef90_I3YHV0 Cluster: 50S ribosomal protein L27 0.18 0.0609 2.3E-01 5.0E-01 -0.0225 8.4E-01 -0.0418 1.6E-01 -0.1247 2.0E-01 -0.0165 8.0E-01 Alistipes_shahii UniRef90_R6WZL7 Cluster: Transcription elongation factor GreA 0.20 0.0723 2.3E-01 5.0E-01 0.1792 1.9E-01 -0.0094 7.9E-01 0.0267 8.2E-01 -0.0087 9.1E-01 Alistipes_shahii UniRef90_D4IJ37 Cluster: Periplasmic protein involved in polysaccharide export 0.13 0.0297 2.3E-01 5.0E-01 0.0554 3.2E-01 -0.0200 1.8E-01 0.0111 8.1E-01 -0.0379 2.4E-01 Alistipes_shahii UniRef90_D4IQG7 Cluster: Dihydroorotase 0.13 0.0296 2.3E-01 5.0E-01 -0.0269 6.4E-01 0.0051 7.3E-01 0.0576 2.1E-01 0.0159 6.2E-01 Alistipes_shahii UniRef90_D4INK8 Cluster: 50S ribosomal protein L9 0.14 0.0514 2.3E-01 5.0E-01 -0.0085 9.3E-01 -0.0086 7.3E-01 0.0341 6.7E-01 -0.0136 8.0E-01

Supplementary Data 3b UniRef90 Family Plasma TMAO Red meat Red meat Choline Choline Species Cluster Name Detection member ID Rate Effect P FDR Effect P Effect P Effect P Effect P Alistipes_shahii UniRef90_D4IPF7 Cluster: Uncharacterized membrane protein (Homolog of Drosophila 0.11 0.0259 2.3E-01 5.0E-01 0.0875 6.5E-02 0.0001 1.0E+00 0.0533 1.8E-01 0.0172 5.3E-01 rhomboid) Alistipes_shahii UniRef90_D4IPY2 Cluster: Glycosyltransferase 0.10 0.0260 2.3E-01 5.0E-01 0.0537 2.7E-01 -0.0134 2.9E-01 -0.0181 6.6E-01 -0.0454 9.7E-02 Alistipes_shahii UniRef90_D4INH4 Cluster: Fumarate hydratase class I 0.20 0.0356 2.4E-01 5.0E-01 0.0510 4.5E-01 -0.0007 9.7E-01 0.0956 9.0E-02 -0.0169 6.5E-01 Alistipes_shahii UniRef90_D4IL07 Cluster: Acylhydrolase 0.16 0.0492 2.4E-01 5.0E-01 0.0513 5.9E-01 0.0081 7.4E-01 -0.0022 9.8E-01 0.0051 9.2E-01 Alistipes_shahii UniRef90_D4IIR9 Cluster: Metal-dependent hydrolases of the beta-lactamase superfamily I 0.11 0.0285 2.4E-01 5.0E-01 0.0112 8.3E-01 0.0080 5.7E-01 0.0764 9.2E-02 -0.0153 6.2E-01 Alistipes_shahii UniRef90_D4INJ8 Cluster: Thioredoxin reductase 0.15 0.0393 2.4E-01 5.1E-01 0.0228 7.6E-01 -0.0399 4.2E-02 0.0001 1.0E+00 -0.0138 7.4E-01 Alistipes_shahii UniRef90_D4IJ56 Cluster: Altronate hydrolase (Fragment) 0.15 0.0315 2.4E-01 5.1E-01 0.0815 1.7E-01 -0.0053 7.3E-01 0.0540 2.9E-01 -0.0301 3.8E-01 Alistipes_shahii UniRef90_D4IPI7 Cluster: Peroxiredoxin 0.15 0.0345 2.4E-01 5.1E-01 0.0361 5.8E-01 0.0065 7.1E-01 0.1108 4.6E-02 -0.0251 5.0E-01 Alistipes_shahii UniRef90_D4IMH8 Cluster: Argininosuccinate synthase 0.17 0.0336 2.4E-01 5.1E-01 0.1274 4.5E-02 0.0113 5.0E-01 0.1706 1.2E-03 0.0130 7.2E-01 Alistipes_shahii UniRef90_D4IPF9 Cluster: Aspartate ammonia-lyase 0.17 0.0343 2.4E-01 5.1E-01 0.0867 1.9E-01 0.0091 5.9E-01 0.0717 2.0E-01 0.0139 7.1E-01 Alistipes_shahii UniRef90_I3YHS0 Cluster: Pyruvate kinase 0.19 0.0391 2.5E-01 5.2E-01 0.0581 4.5E-01 0.0007 9.7E-01 0.0476 4.6E-01 -0.0302 4.8E-01 Alistipes_shahii UniRef90_D4IN30 Cluster: Malic enzyme 0.11 0.0244 2.5E-01 5.2E-01 0.0645 1.7E-01 -0.0114 3.6E-01 0.0095 8.1E-01 0.0241 3.7E-01 Alistipes_shahii UniRef90_D4IPB4 Cluster: Peptide chain release factor 2 0.10 0.0211 2.5E-01 5.2E-01 0.0315 4.4E-01 -0.0211 4.7E-02 0.0010 9.8E-01 -0.0303 1.9E-01 Alistipes_shahii UniRef90_D4IPN5 Cluster: Outer membrane cobalamin receptor protein 0.10 0.0151 2.5E-01 5.2E-01 0.0239 4.3E-01 -0.0016 8.5E-01 0.0311 2.3E-01 -0.0001 1.0E+00 Alistipes_shahii UniRef90_D4IP94 Cluster: PSP1 C-terminal domain-containing protein 0.18 0.0373 2.5E-01 5.2E-01 0.1103 1.3E-01 -0.0213 2.6E-01 0.0550 3.7E-01 -0.0909 2.5E-02 Alistipes_shahii UniRef90_D4IJE9 Cluster: Na(+)-translocating NADH-quinone reductase subunit A 0.15 0.0267 2.5E-01 5.2E-01 0.0606 2.4E-01 -0.0141 3.0E-01 0.0611 1.6E-01 -0.0019 9.5E-01 Alistipes_shahii UniRef90_D4IPU4 Cluster: Alanine dehydrogenase 0.16 0.0340 2.5E-01 5.2E-01 -0.0223 7.4E-01 -0.0066 7.0E-01 0.0666 2.3E-01 -0.0263 4.8E-01 Alistipes_shahii UniRef90_D4IPT6 Cluster: Small-conductance mechanosensitive channel 0.12 0.0263 2.5E-01 5.2E-01 -0.0145 7.8E-01 -0.0053 7.1E-01 0.0205 6.5E-01 0.0284 3.5E-01 Alistipes_shahii UniRef90_D4IP42 Cluster: Outer membrane protein 0.12 0.0230 2.5E-01 5.2E-01 0.0839 6.0E-02 0.0105 3.8E-01 0.0517 1.7E-01 0.0031 9.0E-01 Alistipes_shahii UniRef90_I3YPZ8 Cluster: Methylglyoxal synthase 0.12 0.0388 2.5E-01 5.2E-01 0.0671 3.8E-01 -0.0294 1.4E-01 0.0869 1.8E-01 -0.0765 7.5E-02 Alistipes_shahii UniRef90_D4IP58 Cluster: Thiol-disulfide isomerase and thioredoxins 0.15 0.0298 2.6E-01 5.3E-01 -0.0097 8.7E-01 -0.0088 5.8E-01 0.0664 1.8E-01 -0.0028 9.3E-01 Alistipes_shahii UniRef90_D4IMB2 Cluster: Transcriptional regulator 0.14 0.0305 2.6E-01 5.3E-01 -0.0477 4.4E-01 0.0036 8.2E-01 -0.0116 8.2E-01 0.0049 8.9E-01 Alistipes_shahii UniRef90_D4IIN8 Cluster: Ribosome maturation factor RimP 0.11 0.0368 2.6E-01 5.3E-01 0.0407 5.8E-01 -0.0103 5.9E-01 0.0151 8.1E-01 -0.0140 7.4E-01 Alistipes_shahii UniRef90_D4IL05 Cluster: Xaa-Pro aminopeptidase 0.21 0.0473 2.6E-01 5.3E-01 0.0358 7.2E-01 -0.0029 9.1E-01 0.1152 1.6E-01 -0.0525 3.2E-01 Alistipes_shahii UniRef90_D4IK08 Cluster: Homoserine acetyltransferase 0.14 0.0442 2.6E-01 5.3E-01 0.0935 2.9E-01 -0.0272 2.4E-01 0.0707 3.4E-01 -0.0053 9.1E-01 Alistipes_shahii UniRef90_R6VTP9 Cluster: Enolase 0.22 0.0563 2.6E-01 5.3E-01 0.1089 3.4E-01 -0.0368 2.0E-01 0.1174 2.2E-01 -0.0691 2.7E-01 Alistipes_shahii UniRef90_D4INS6 Cluster: Tyrosine phenol-lyase 0.19 0.0496 2.6E-01 5.3E-01 0.0286 7.8E-01 -0.0124 6.2E-01 -0.0147 8.6E-01 -0.0181 7.4E-01 Alistipes_shahii UniRef90_D4IQQ1 Cluster: Thiol:disulfide interchange protein 0.10 0.0262 2.6E-01 5.3E-01 0.0143 7.8E-01 0.0057 6.8E-01 0.0926 3.4E-02 0.0045 8.8E-01 Alistipes_shahii UniRef90_D4IPZ2 Cluster: DNA/RNA endonuclease G, NUC1 0.16 0.0425 2.6E-01 5.3E-01 0.0927 2.8E-01 -0.0034 8.8E-01 0.0701 3.3E-01 -0.0454 3.5E-01 Alistipes_shahii UniRef90_I3YMY1 Cluster: 50S ribosomal protein L11 0.22 0.0588 2.7E-01 5.3E-01 0.0208 8.6E-01 -0.0047 8.8E-01 0.0379 7.1E-01 -0.0678 3.1E-01 Alistipes_shahii UniRef90_D4IMB8 Cluster: 2-keto-4-pentenoate hydratase/2-oxohepta-3-ene-1,7-dioic acid 0.12 0.0320 2.7E-01 5.4E-01 0.0015 9.8E-01 -0.0067 6.9E-01 0.0771 1.5E-01 -0.0576 1.2E-01 hydratase (Catechol pathway) Alistipes_shahii UniRef90_D4IM09 Cluster: Ribosomal RNA small subunit methyltransferase H 0.15 0.0361 2.7E-01 5.4E-01 0.0531 4.8E-01 0.0045 8.1E-01 0.0805 1.9E-01 -0.0249 5.4E-01 Alistipes_shahii UniRef90_D4INA9 Cluster: Murein DD-endopeptidase MepM and murein hydrolase activator 0.13 0.0239 2.7E-01 5.4E-01 0.0538 2.6E-01 -0.0010 9.4E-01 0.0542 1.8E-01 -0.0089 7.5E-01 NlpD, contain LysM domain Alistipes_shahii UniRef90_I3YMD4 Cluster: Lipocalin-like domain-containing protein 0.16 0.0505 2.7E-01 5.4E-01 -0.0160 8.8E-01 0.0051 8.5E-01 0.0902 3.0E-01 0.0788 1.6E-01 Alistipes_shahii UniRef90_D4IL95 Cluster: Aminoacyl-histidine dipeptidase 0.20 0.0498 2.7E-01 5.4E-01 0.1861 6.9E-02 0.0211 4.2E-01 0.0909 2.9E-01 0.0022 9.7E-01 Alistipes_shahii UniRef90_D4IN23 Cluster: Phosphatidylglycerol--prolipoprotein diacylglyceryl transferase 0.17 0.0355 2.7E-01 5.4E-01 0.1463 3.8E-02 -0.0032 8.7E-01 0.0737 2.2E-01 -0.0310 4.5E-01 Alistipes_shahii UniRef90_R6Z1T1 Cluster: Chaperone protein DnaJ 0.17 0.0358 2.7E-01 5.4E-01 0.0908 2.2E-01 -0.0241 2.0E-01 0.0802 1.9E-01 -0.0372 3.6E-01 Alistipes_shahii UniRef90_D4IQE9 Cluster: Phosphoribosylamine--glycine ligase 0.13 0.0232 2.7E-01 5.4E-01 0.0349 4.6E-01 -0.0243 5.1E-02 0.0387 3.3E-01 -0.0239 3.7E-01 Alistipes_shahii UniRef90_D4IKB3 Cluster: Chondroitin sulfate ABC lyase 0.19 0.0374 2.7E-01 5.4E-01 0.0473 5.4E-01 0.0046 8.2E-01 0.1768 6.0E-03 -0.0226 6.0E-01 Alistipes_shahii UniRef90_D4IKT4 Cluster: Transcriptional regulators 0.11 0.0235 2.7E-01 5.4E-01 0.0086 8.6E-01 -0.0012 9.2E-01 0.1397 4.8E-04 0.0220 4.1E-01 Alistipes_shahii UniRef90_R6W1I4 Cluster: Serine hydroxymethyltransferase 0.20 0.0407 2.7E-01 5.4E-01 0.0151 8.6E-01 -0.0208 3.4E-01 0.0550 4.4E-01 -0.0117 8.0E-01 Alistipes_shahii UniRef90_I3YM18 Cluster: 50S ribosomal protein L23 0.18 0.0486 2.7E-01 5.4E-01 0.1042 3.0E-01 -0.0350 1.9E-01 0.1253 1.4E-01 -0.0406 4.8E-01 Alistipes_shahii UniRef90_D4IMD5 Cluster: UDP-N-acetylglucosamine--N-acetylmuramyl-(pentapeptide) 0.16 0.0365 2.7E-01 5.4E-01 0.1240 9.9E-02 0.0260 1.8E-01 0.1180 6.3E-02 -0.0094 8.2E-01 pyrophosphoryl-undecaprenol N-acetylglucosamine transferase Alistipes_shahii UniRef90_D4IKB9 Cluster: Mannose-6-phosphate isomerase, type 1 0.14 0.0304 2.8E-01 5.4E-01 0.0544 3.9E-01 -0.0211 2.0E-01 0.0119 8.2E-01 -0.0443 2.2E-01 Alistipes_shahii UniRef90_D4ILH7 Cluster: Ribosome maturation factor RimM 0.15 0.0621 2.8E-01 5.5E-01 0.0931 4.7E-01 -0.0145 6.6E-01 0.1101 3.2E-01 -0.0779 2.8E-01 Alistipes_shahii UniRef90_UPI00036657AD Cluster: Aspartate-semialdehyde dehydrogenase 0.17 0.0341 2.8E-01 5.5E-01 0.0833 2.4E-01 0.0053 7.7E-01 0.1215 3.9E-02 -0.0319 4.2E-01 Alistipes_shahii UniRef90_D4IMS2 Cluster: Cation diffusion facilitator family transporter 0.11 0.0230 2.8E-01 5.5E-01 0.0165 7.3E-01 -0.0054 6.7E-01 0.0834 3.7E-02 -0.0246 3.6E-01 Alistipes_shahii UniRef90_D4IQF4 Cluster: Metal-dependent hydrolase 0.13 0.0247 2.9E-01 5.5E-01 0.1046 3.9E-02 0.0135 3.2E-01 0.0448 3.1E-01 0.0159 5.9E-01 Alistipes_shahii UniRef90_D4INL2 Cluster: Thiamine-monophosphate kinase 0.19 0.0488 2.9E-01 5.6E-01 0.0567 5.9E-01 -0.0203 4.5E-01 0.0307 7.3E-01 -0.0457 4.3E-01 Alistipes_shahii UniRef90_D4IN15 Cluster: Ribulose-phosphate 3-epimerase 0.14 0.0437 2.9E-01 5.6E-01 0.0872 3.6E-01 -0.0008 9.7E-01 -0.0011 9.9E-01 -0.0038 9.4E-01 Alistipes_shahii UniRef90_I3YQ92 Cluster: Pyrophosphate--fructose 6-phosphate 1-phosphotransferase 0.20 0.0511 2.9E-01 5.6E-01 0.0498 6.5E-01 -0.0190 5.1E-01 0.1174 2.1E-01 -0.0061 9.2E-01 Alistipes_shahii UniRef90_D4IQ58 Cluster: Transcriptional regulator 0.10 0.0202 2.9E-01 5.6E-01 0.0285 5.0E-01 -0.0182 1.1E-01 0.0255 4.9E-01 -0.0177 4.8E-01 Alistipes_shahii UniRef90_R7JHR5 Cluster: Phosphoenolpyruvate carboxykinase (ATP) 0.25 0.0487 2.9E-01 5.6E-01 0.0098 9.3E-01 -0.0564 3.5E-02 0.1064 2.4E-01 -0.0612 2.9E-01 Alistipes_shahii UniRef90_D4ILS0 Cluster: Predicted Zn-dependent hydrolases of the beta-lactamase fold 0.12 0.0258 3.0E-01 5.6E-01 0.0413 4.5E-01 -0.0081 5.8E-01 0.0321 4.8E-01 -0.0237 4.5E-01 Alistipes_shahii UniRef90_D4INR1 Cluster: BirA, biotin-[acetyl-CoA-carboxylase] ligase region 0.19 0.0503 3.0E-01 5.6E-01 0.1741 1.2E-01 -0.0125 6.5E-01 0.2363 1.0E-02 -0.0207 7.3E-01 Alistipes_shahii UniRef90_D4ILU4 Cluster: Folylpolyglutamate synthase/dihydrofolate synthase 0.11 0.0188 3.0E-01 5.6E-01 0.0214 5.9E-01 0.0006 9.5E-01 0.0258 4.5E-01 0.0077 7.4E-01 Alistipes_shahii UniRef90_I3YMD1 Cluster: SusD family 0.20 0.0402 3.0E-01 5.6E-01 -0.0181 8.4E-01 -0.0097 6.6E-01 -0.0298 6.9E-01 0.0069 8.9E-01 Alistipes_shahii UniRef90_D4IIP6 Cluster: Predicted dehydrogenases and related proteins 0.17 0.0366 3.0E-01 5.6E-01 0.0429 5.9E-01 0.0163 4.3E-01 0.0447 5.1E-01 -0.0088 8.4E-01 Alistipes_shahii UniRef90_D4IJ26 Cluster: Predicted DNA alkylation repair enzyme 0.15 0.0566 3.0E-01 5.6E-01 0.0580 6.4E-01 -0.0085 7.9E-01 -0.0043 9.7E-01 -0.0496 4.7E-01 Alistipes_shahii UniRef90_I3YKJ3 Cluster: 6,7-dimethyl-8-ribityllumazine synthase 0.17 0.0460 3.1E-01 5.7E-01 0.1349 1.9E-01 0.0176 5.0E-01 0.0542 5.3E-01 -0.0488 3.9E-01 Alistipes_shahii UniRef90_D4ILI3 Cluster: Chorismate synthase 0.19 0.0471 3.1E-01 5.7E-01 0.0013 9.9E-01 -0.0294 2.7E-01 0.0739 4.0E-01 -0.0860 1.3E-01 Alistipes_shahii UniRef90_D4IJQ4 Cluster: Histidine--tRNA ligase 0.15 0.0257 3.1E-01 5.8E-01 0.0132 8.1E-01 -0.0105 4.8E-01 0.0520 2.8E-01 -0.0369 2.5E-01 Alistipes_shahii UniRef90_D4IK07 Cluster: Transcriptional regulator 0.15 0.0375 3.1E-01 5.8E-01 0.1165 1.5E-01 -0.0132 5.4E-01 0.0853 2.1E-01 -0.0180 7.0E-01 Alistipes_shahii UniRef90_I3YPW5 Cluster: Preprotein translocase YajC subunit 0.14 0.0511 3.1E-01 5.8E-01 0.1024 3.6E-01 0.0166 5.7E-01 -0.0214 8.2E-01 -0.0423 5.0E-01 Alistipes_shahii UniRef90_D4IP69 Cluster: DUF4301 domain-containing protein 0.21 0.0420 3.1E-01 5.8E-01 0.0701 4.6E-01 -0.0016 9.4E-01 0.1051 1.8E-01 -0.0260 6.1E-01 Alistipes_shahii UniRef90_D4ILR1 Cluster: SAM-dependent methyltransferase 0.12 0.0184 3.1E-01 5.8E-01 0.0368 3.7E-01 -0.0090 4.0E-01 0.0341 3.2E-01 -0.0202 3.8E-01 Alistipes_shahii UniRef90_D4IMW3 Cluster: Predicted phosphohydrolases 0.13 0.0261 3.1E-01 5.8E-01 0.0122 8.4E-01 -0.0129 3.8E-01 0.0886 7.2E-02 -0.0797 1.3E-02 Alistipes_shahii UniRef90_I3YM36 Cluster: 50S ribosomal protein L15 0.17 0.0548 3.1E-01 5.8E-01 0.1103 3.7E-01 0.0299 3.5E-01 0.0435 6.8E-01 0.0362 6.0E-01 Alistipes_shahii UniRef90_D4IP84 Cluster: S-adenosylmethionine synthase 0.18 0.0335 3.1E-01 5.8E-01 0.0922 2.2E-01 -0.0071 7.1E-01 0.0625 3.2E-01 -0.0572 1.7E-01 Alistipes_shahii UniRef90_D4INA2 Cluster: Short-chain dehydrogenases of various substrate specificities 0.14 0.0364 3.1E-01 5.8E-01 0.1439 7.4E-02 0.0082 7.0E-01 0.0783 2.5E-01 0.0469 3.0E-01 Alistipes_shahii UniRef90_I3YL92 Cluster: Magnesium transport protein CorA 0.13 0.0192 3.1E-01 5.8E-01 0.0821 5.3E-02 -0.0101 3.6E-01 0.0339 3.5E-01 -0.0030 9.0E-01 Alistipes_shahii UniRef90_D4IKA6 Cluster: Malonyl CoA-acyl carrier protein transacylase 0.14 0.0294 3.1E-01 5.8E-01 0.0767 2.3E-01 0.0258 1.3E-01 0.1062 5.1E-02 0.0375 3.1E-01 Alistipes_shahii UniRef90_D4IQN7 Cluster: Uncharacterized ArCR, COG2043 0.14 0.0382 3.2E-01 5.8E-01 0.1203 1.7E-01 -0.0121 5.8E-01 0.0863 2.3E-01 -0.0640 1.7E-01 Alistipes_shahii UniRef90_D4IKV4 Cluster: Beta-galactosidase/beta-glucuronidase 0.21 0.0542 3.2E-01 5.8E-01 0.0097 9.4E-01 -0.0358 2.5E-01 0.1041 3.2E-01 -0.0208 7.6E-01 Alistipes_shahii UniRef90_D4IQI1 Cluster: Adenine DNA glycosylase 0.10 0.0199 3.2E-01 5.8E-01 0.0421 3.5E-01 -0.0069 5.6E-01 0.0223 5.6E-01 -0.0087 7.3E-01 Alistipes_shahii UniRef90_D4IM44 Cluster: Dipeptidyl-peptidase 0.19 0.0293 3.2E-01 5.8E-01 0.1129 8.7E-02 0.0264 1.2E-01 0.0799 1.5E-01 0.0029 9.4E-01 Alistipes_shahii UniRef90_D4IJ89 Cluster: 3-oxo-5-alpha-steroid 4-dehydrogenase 0.11 0.0234 3.2E-01 5.8E-01 -0.0175 7.4E-01 0.0077 5.8E-01 0.0094 8.3E-01 0.0026 9.3E-01 Alistipes_shahii UniRef90_D4IQ64 Cluster: 3-deoxy-manno-octulosonate cytidylyltransferase 0.14 0.0397 3.2E-01 5.8E-01 0.0524 5.6E-01 0.0072 7.6E-01 -0.0014 9.9E-01 -0.0160 7.5E-01 Alistipes_shahii UniRef90_D4IPC7 Cluster: Predicted SAM-dependent methyltransferases 0.14 0.0299 3.2E-01 5.9E-01 0.0850 2.1E-01 0.0036 8.4E-01 0.0825 1.5E-01 -0.0606 1.1E-01 Alistipes_shahii UniRef90_D4IJR4 Cluster: ABC-type multidrug transport system, permease component 0.15 0.0321 3.2E-01 5.9E-01 0.0916 2.1E-01 -0.0006 9.7E-01 0.0926 1.3E-01 -0.0278 5.0E-01 Alistipes_shahii UniRef90_D4INA0 Cluster: Deoxycytidylate deaminase 0.12 0.0295 3.2E-01 5.8E-01 0.1021 1.2E-01 0.0020 9.1E-01 0.0610 2.7E-01 -0.0140 7.1E-01 Alistipes_shahii UniRef90_I3YPM3 Cluster: GMP synthase [glutamine-hydrolyzing] 0.20 0.0404 3.2E-01 5.8E-01 0.0547 5.6E-01 -0.0054 8.2E-01 0.0471 5.5E-01 -0.0325 5.2E-01 Alistipes_shahii UniRef90_D4IMF4 Cluster: Cell division protein FtsX 0.15 -0.0371 3.2E-01 5.8E-01 0.1399 9.7E-02 0.0089 6.8E-01 0.1391 4.9E-02 0.0265 5.7E-01 Alistipes_shahii UniRef90_I3YM26 Cluster: 50S ribosomal protein L14 0.19 0.0452 3.2E-01 5.8E-01 0.1344 2.0E-01 -0.0266 3.3E-01 0.0559 5.3E-01 -0.0308 6.0E-01 Alistipes_shahii UniRef90_D4INT9 Cluster: Muramidase (Flagellum-specific) 0.14 0.0240 3.3E-01 5.8E-01 0.0366 5.1E-01 -0.0078 5.9E-01 0.0179 7.0E-01 -0.0139 6.5E-01 Alistipes_shahii UniRef90_I3YM23 Cluster: 50S ribosomal protein L16 0.20 0.0491 3.3E-01 5.8E-01 0.1095 3.4E-01 -0.0499 9.1E-02 0.0490 6.1E-01 0.0147 8.2E-01 Alistipes_shahii UniRef90_D4IKB6 Cluster: Arylsulfatase A and related enzymes 0.18 0.0384 3.3E-01 5.8E-01 0.1022 2.6E-01 0.0049 8.3E-01 0.0799 2.9E-01 -0.0665 1.8E-01 Alistipes_shahii UniRef90_D4ING8 Cluster: Nitroreductase 0.12 0.0185 3.3E-01 5.8E-01 0.0346 4.1E-01 0.0124 2.6E-01 0.0312 3.8E-01 0.0083 7.3E-01 Alistipes_shahii UniRef90_D4IQ67 Cluster: Peroxiredoxin 0.10 0.0175 3.3E-01 5.8E-01 0.0274 4.8E-01 -0.0034 7.5E-01 0.0264 4.3E-01 -0.0111 6.3E-01 Alistipes_shahii UniRef90_I3YM44 Cluster: DNA-directed RNA polymerase subunit alpha 0.22 0.0470 3.3E-01 5.9E-01 0.0775 4.8E-01 0.0048 8.6E-01 0.0205 8.2E-01 -0.0155 8.0E-01 49

Supplementary Data 3b UniRef90 Family Plasma TMAO Red meat Red meat Choline Choline Species Cluster Name Detection member ID Rate Effect P FDR Effect P Effect P Effect P Effect P Alistipes_shahii UniRef90_D4IJP6 Cluster: Galactose mutarotase and related enzymes 0.19 0.0533 3.3E-01 5.9E-01 0.0590 6.4E-01 0.0001 1.0E+00 0.1250 2.3E-01 -0.0837 2.2E-01 Alistipes_shahii UniRef90_D4IIS2 Cluster: Outer membrane protein 0.14 0.0259 3.4E-01 5.9E-01 0.0799 1.8E-01 0.0089 5.7E-01 0.0149 7.7E-01 -0.0106 7.5E-01 Alistipes_shahii UniRef90_I3YQC1 Cluster: Elongation factor Ts 0.20 0.0469 3.4E-01 5.9E-01 -0.0305 7.8E-01 -0.0025 9.3E-01 -0.0021 9.8E-01 -0.0638 3.0E-01 Alistipes_shahii UniRef90_I3YM22 Cluster: 30S ribosomal protein S3 0.23 0.0509 3.4E-01 5.9E-01 -0.0713 5.7E-01 -0.0137 6.6E-01 0.0753 4.7E-01 0.0005 9.9E-01 Alistipes_shahii UniRef90_R5UBB0 Cluster: Undecaprenyl-diphosphatase 0.15 0.0288 3.4E-01 5.9E-01 0.0583 3.8E-01 0.0098 5.8E-01 0.1576 4.5E-03 -0.0159 6.8E-01 Alistipes_shahii UniRef90_D4IQ42 Cluster: Pantothenate synthetase 0.13 0.0286 3.4E-01 5.9E-01 0.0627 3.4E-01 -0.0219 2.1E-01 0.0297 6.0E-01 -0.0524 1.6E-01 Alistipes_shahii UniRef90_F3PNI3 Cluster: Non-receptor tyrosine-protein kinase TNK1 0.14 0.0210 3.4E-01 5.9E-01 0.0225 6.4E-01 -0.0032 8.0E-01 0.0380 3.5E-01 -0.0027 9.2E-01 Alistipes_shahii UniRef90_D4IL33 Cluster: BACON domain-containing protein 0.12 -0.0284 3.5E-01 6.0E-01 0.0065 9.2E-01 0.0020 9.1E-01 0.0015 9.8E-01 0.0753 4.5E-02 Alistipes_shahii UniRef90_D4IQG6 Cluster: Carbamoyl-phosphate synthase small chain 0.12 0.0194 3.5E-01 6.0E-01 -0.0293 5.3E-01 0.0045 7.2E-01 0.0067 8.7E-01 0.0007 9.8E-01 Alistipes_shahii UniRef90_D4ILH9 Cluster: FOG: CheY-like receiver 0.11 0.0247 3.5E-01 6.0E-01 -0.0069 9.1E-01 0.0097 5.3E-01 0.0680 1.7E-01 -0.0234 4.8E-01 Alistipes_shahii UniRef90_D4IKB1 Cluster: SusD family 0.15 0.0224 3.5E-01 6.0E-01 0.0171 7.5E-01 -0.0053 7.0E-01 0.0315 4.9E-01 -0.0383 2.0E-01 Alistipes_shahii UniRef90_D4IJF1 Cluster: Na(+)-translocating NADH-quinone reductase subunit C 0.12 0.0221 3.5E-01 6.0E-01 0.0413 4.3E-01 -0.0089 5.3E-01 0.0070 8.8E-01 -0.0001 1.0E+00 Alistipes_shahii UniRef90_I3YIH2 Cluster: RNA polymerase sigma factor rpoD 0.23 0.0459 3.5E-01 6.0E-01 0.0730 5.2E-01 -0.0452 1.1E-01 0.0523 5.8E-01 -0.0258 6.7E-01 Alistipes_shahii UniRef90_Q8A2S4 Cluster: 4-deoxy-L-threo-5-hexosulose-uronate ketol-isomerase 1 0.17 0.0416 3.5E-01 6.0E-01 0.0868 3.9E-01 0.0003 9.9E-01 0.1375 9.9E-02 -0.0446 4.2E-01 Alistipes_shahii UniRef90_R6VGE9 Cluster: Methionine import ATP-binding protein MetN 2 0.13 0.0208 3.5E-01 6.0E-01 0.1056 3.1E-02 0.0056 6.7E-01 0.0138 7.4E-01 0.0078 7.8E-01 Alistipes_shahii UniRef90_UPI00037C1B4F Cluster: Thiol:disulfide interchange protein DsbD 0.11 0.0252 3.5E-01 6.0E-01 0.0174 7.7E-01 0.0031 8.5E-01 0.0249 6.1E-01 0.0196 5.7E-01 Alistipes_shahii UniRef90_I3YI43 Cluster: 3-oxoacyl-[acyl-carrier-protein] synthase 2 0.23 0.0533 3.5E-01 6.0E-01 -0.0191 8.9E-01 0.0043 9.0E-01 0.0300 7.9E-01 0.0023 9.7E-01 Alistipes_shahii UniRef90_D4ILP0 Cluster: Hypoxanthine phosphoribosyltransferase 0.11 0.0267 3.5E-01 6.0E-01 0.0697 2.7E-01 -0.0083 6.2E-01 0.0394 4.6E-01 -0.0138 7.0E-01 Alistipes_shahii UniRef90_D4ING0 Cluster: Lysophospholipase L1 and related esterases 0.15 0.0387 3.5E-01 6.0E-01 -0.0034 9.7E-01 0.0111 6.5E-01 0.1620 3.9E-02 -0.0172 7.4E-01 Alistipes_shahii UniRef90_D4ILF1 Cluster: Acetyltransferase (GNAT) family 0.14 0.0384 3.5E-01 6.0E-01 0.1820 5.0E-02 -0.0164 4.9E-01 0.1002 2.0E-01 -0.0591 2.5E-01 Alistipes_shahii UniRef90_D4IIN2 Cluster: Probable sensor-like histidine kinase YehU 0.13 0.0198 3.6E-01 6.0E-01 0.0314 5.1E-01 0.0040 7.5E-01 0.0151 7.1E-01 -0.0446 1.0E-01 Alistipes_shahii UniRef90_D4IJR3 Cluster: Multidrug resistance efflux pump 0.19 0.0389 3.6E-01 6.0E-01 0.0403 6.8E-01 -0.0157 5.3E-01 0.0789 3.3E-01 -0.0116 8.3E-01 Alistipes_shahii UniRef90_D4IJS1 Cluster: Rho termination factor, RNA-binding domain 0.12 0.0208 3.6E-01 6.1E-01 -0.0246 6.3E-01 0.0001 1.0E+00 -0.0274 5.2E-01 0.0326 2.5E-01 Alistipes_shahii UniRef90_D4ILR5 Cluster: TonB_dep_Rec domain-containing protein 0.17 0.0222 3.6E-01 6.1E-01 0.0764 1.6E-01 -0.0158 2.7E-01 0.0555 2.3E-01 0.0036 9.1E-01 Alistipes_shahii UniRef90_D4IIN3 Cluster: LytTr DNA-binding domain protein 0.11 0.0206 3.6E-01 6.1E-01 0.0099 8.4E-01 -0.0101 4.5E-01 0.0337 4.3E-01 -0.0195 5.0E-01 Alistipes_shahii UniRef90_D4IK35 Cluster: Dipeptidase 0.19 0.0298 3.6E-01 6.1E-01 0.0782 2.9E-01 -0.0198 3.1E-01 0.1212 5.1E-02 -0.0659 1.2E-01 Alistipes_shahii UniRef90_I3YPM0 Cluster: 3-methyl-2-oxobutanoate hydroxymethyltransferase 0.13 0.0279 3.6E-01 6.1E-01 0.0114 8.7E-01 -0.0288 1.1E-01 -0.0079 8.9E-01 -0.0326 4.0E-01 Alistipes_shahii UniRef90_I3YJR0 Cluster: Sulfide dehydrogenase (Flavoprotein) subunit SudB 0.16 0.0304 3.6E-01 6.1E-01 0.0371 6.3E-01 -0.0155 4.3E-01 0.1223 5.5E-02 -0.0713 9.5E-02 Alistipes_shahii UniRef90_I3YKF9 Cluster: 30S ribosomal protein S18 0.14 0.0354 3.7E-01 6.1E-01 -0.0078 9.3E-01 -0.0147 5.2E-01 -0.0767 2.9E-01 -0.0193 7.0E-01 Alistipes_shahii UniRef90_D4IKB2 Cluster: Outer membrane receptor proteins, mostly Fe transport 0.18 0.0289 3.7E-01 6.1E-01 0.0084 9.1E-01 -0.0134 4.8E-01 0.0808 1.8E-01 -0.0289 4.8E-01 Alistipes_shahii UniRef90_D4ILK5 Cluster: Glutamine-dependent NAD(+) synthetase 0.21 0.0388 3.7E-01 6.1E-01 0.0422 6.7E-01 -0.0139 5.8E-01 0.0164 8.4E-01 -0.0439 4.1E-01 Alistipes_shahii UniRef90_D4IJN8 Cluster: Uridine phosphorylase 0.18 0.0375 3.7E-01 6.1E-01 0.1495 1.2E-01 0.0042 8.6E-01 0.0997 2.1E-01 -0.0371 4.8E-01 Alistipes_shahii UniRef90_D4ILQ0 Cluster: Acetate kinase 0.18 0.0326 3.7E-01 6.1E-01 0.0502 5.4E-01 0.0024 9.1E-01 -0.0290 6.7E-01 0.0076 8.7E-01 Alistipes_shahii UniRef90_D4IJQ1 Cluster: Predicted membrane protein 0.16 0.0239 3.7E-01 6.1E-01 0.0505 4.0E-01 -0.0034 8.3E-01 0.0033 9.5E-01 0.0290 3.9E-01 Alistipes_shahii UniRef90_D4IJM4 Cluster: Predicted membrane-associated, metal-dependent hydrolase 0.12 0.0173 3.7E-01 6.1E-01 0.1026 1.5E-02 -0.0117 3.1E-01 -0.0244 5.0E-01 0.0418 8.9E-02 Alistipes_shahii UniRef90_D4IP35 Cluster: Acetyl-CoA hydrolase 0.15 0.0323 3.7E-01 6.1E-01 -0.0256 7.5E-01 -0.0253 2.3E-01 -0.0024 9.7E-01 -0.0434 3.4E-01 Alistipes_shahii UniRef90_D4IQL0 Cluster: PMT_2 domain-containing protein 0.16 0.0229 3.7E-01 6.1E-01 0.0880 1.2E-01 0.0048 7.5E-01 0.0303 5.3E-01 0.0057 8.6E-01 Alistipes_shahii UniRef90_D4IMV4 Cluster: FAD_binding_3 domain-containing protein 0.13 -0.0215 3.7E-01 6.1E-01 -0.0211 6.9E-01 -0.0097 4.9E-01 0.0006 9.9E-01 -0.0245 4.2E-01 Alistipes_shahii UniRef90_D4IJJ3 Cluster: Histidine ammonia-lyase 0.19 0.0381 3.7E-01 6.1E-01 0.1467 1.3E-01 0.0025 9.2E-01 0.0889 2.7E-01 0.0135 8.0E-01 Alistipes_shahii UniRef90_D4IJ06 Cluster: O-Glycosyl hydrolase 0.12 0.0225 3.7E-01 6.1E-01 0.0592 2.8E-01 0.0066 6.6E-01 0.0115 8.1E-01 -0.0381 2.4E-01 Alistipes_shahii UniRef90_D4IP59 Cluster: UDP-3-O-acylglucosamine N-acyltransferase 0.18 0.0327 3.8E-01 6.2E-01 -0.0485 5.6E-01 -0.0003 9.9E-01 0.0510 4.6E-01 0.0135 7.7E-01 Alistipes_shahii UniRef90_R6Y6U7 Cluster: Aspartate--tRNA ligase 0.17 0.0232 3.8E-01 6.2E-01 0.0337 5.7E-01 0.0010 9.5E-01 -0.0158 7.5E-01 -0.0172 6.0E-01 Alistipes_shahii UniRef90_D4IJP0 Cluster: DNA polymerase III, epsilon subunit and related 3'-5' exonucleases 0.22 0.0480 3.8E-01 6.2E-01 0.0668 6.0E-01 -0.0074 8.1E-01 0.0810 4.4E-01 -0.0464 4.9E-01 Alistipes_shahii UniRef90_D4IPZ7 Cluster: Endolytic murein transglycosylase 0.10 0.0146 3.9E-01 6.2E-01 0.0007 9.8E-01 -0.0115 2.5E-01 -0.0095 7.6E-01 -0.0106 6.2E-01 Alistipes_shahii UniRef90_D4IIR1 Cluster: tRNA N6-adenosine threonylcarbamoyltransferase 0.12 0.0176 3.9E-01 6.3E-01 0.0591 2.0E-01 -0.0046 7.1E-01 0.0182 6.4E-01 0.0169 5.2E-01 Alistipes_shahii UniRef90_R6B568 Cluster: 2-dehydro-3-deoxygluconokinase 0.15 0.0271 3.9E-01 6.3E-01 0.1478 3.4E-02 -0.0053 7.7E-01 0.0666 2.6E-01 -0.0252 5.3E-01 Alistipes_shahii UniRef90_D4IKX0 Cluster: Heme chaperone HemW 0.14 0.0266 3.9E-01 6.3E-01 -0.0073 9.2E-01 0.0032 8.6E-01 0.0858 1.4E-01 -0.0167 6.7E-01 Alistipes_shahii UniRef90_D4IM95 Cluster: Dipeptidyl-peptidase 0.15 0.0191 3.9E-01 6.3E-01 -0.0118 8.1E-01 -0.0037 7.8E-01 -0.0185 6.6E-01 -0.0509 6.8E-02 Alistipes_shahii UniRef90_D4IQD6 Cluster: S1/P1 Nuclease 0.16 0.0256 3.9E-01 6.3E-01 0.0204 7.6E-01 -0.0069 6.9E-01 0.0601 2.8E-01 0.0091 8.1E-01 Alistipes_shahii UniRef90_I3YND8 Cluster: Kinase, PfkB family 0.16 0.0297 3.9E-01 6.3E-01 0.0967 2.1E-01 -0.0050 8.0E-01 0.0312 6.3E-01 -0.0031 9.4E-01 Alistipes_shahii UniRef90_D4INB9 Cluster: Metal-dependent hydrolase 0.13 0.0399 3.9E-01 6.3E-01 0.0337 7.5E-01 0.0198 4.6E-01 0.0322 7.1E-01 -0.0117 8.4E-01 Alistipes_shahii UniRef90_D4IPG2 Cluster: UDP-glucose 6-dehydrogenase 0.13 0.0211 3.9E-01 6.3E-01 0.1152 3.9E-02 -0.0170 2.3E-01 0.0294 5.3E-01 -0.0124 6.9E-01 Alistipes_shahii UniRef90_D4IKY3 Cluster: TPR_REGION domain-containing protein 0.25 0.0626 4.0E-01 6.3E-01 0.0161 9.3E-01 -0.0407 3.4E-01 0.1066 4.6E-01 -0.0772 3.9E-01 Alistipes_shahii UniRef90_D4IMD4 Cluster: Mg chelatase-related protein 0.18 0.0299 4.0E-01 6.3E-01 0.0297 7.0E-01 -0.0160 4.4E-01 0.0771 2.4E-01 -0.0572 2.0E-01 Alistipes_shahii UniRef90_E1WUQ9 Cluster: YncE family protein 0.12 -0.0123 4.0E-01 6.3E-01 -0.0220 5.0E-01 -0.0011 8.9E-01 0.0243 3.8E-01 0.0027 8.9E-01 Alistipes_shahii UniRef90_D4IMC3 Cluster: 23S rRNA m(5)U-1939 methyltransferase 0.15 -0.0182 4.0E-01 6.3E-01 -0.0765 1.2E-01 0.0009 9.5E-01 0.0575 1.6E-01 -0.0282 3.0E-01 Alistipes_shahii UniRef90_D4IKX1 Cluster: Alpha-glucan phosphorylases 0.21 0.0189 4.0E-01 6.3E-01 0.0965 6.0E-02 -0.0082 5.3E-01 0.0312 4.7E-01 -0.0455 1.0E-01 Alistipes_shahii UniRef90_D4IJ19 Cluster: Dephospho-CoA kinase 0.12 0.0277 4.0E-01 6.4E-01 -0.0178 8.1E-01 -0.0279 1.6E-01 0.0511 4.2E-01 -0.0511 2.3E-01 Alistipes_shahii UniRef90_D4IJN2 Cluster: Alpha/beta hydrolase 0.16 0.0310 4.0E-01 6.4E-01 0.0366 6.6E-01 -0.0213 3.2E-01 0.0614 3.8E-01 -0.0323 4.9E-01 Alistipes_shahii UniRef90_D4IJT8 Cluster: S1/P1 Nuclease 0.11 0.0167 4.0E-01 6.4E-01 0.0261 5.5E-01 -0.0005 9.6E-01 0.0208 5.7E-01 -0.0024 9.2E-01 Alistipes_shahii UniRef90_D4IJZ2 Cluster: L,D-transpeptidase 0.10 -0.0237 4.1E-01 6.4E-01 0.0176 7.8E-01 -0.0064 7.0E-01 0.0525 3.2E-01 -0.0182 6.1E-01 Alistipes_shahii UniRef90_D4ILJ9 Cluster: K+ transport system, NAD-binding component 0.21 0.0342 4.1E-01 6.4E-01 0.0896 3.5E-01 -0.0179 4.5E-01 0.0589 4.6E-01 -0.0222 6.7E-01 Alistipes_shahii UniRef90_R7JJP7 Cluster: 50S ribosomal protein L5 0.20 0.0431 4.1E-01 6.4E-01 0.0534 6.5E-01 -0.0445 1.4E-01 -0.0046 9.6E-01 -0.1145 8.0E-02 Alistipes_shahii UniRef90_R6Y9C4 Cluster: Elongation factor 4 0.17 0.0156 4.2E-01 6.5E-01 -0.0242 5.8E-01 -0.0097 4.0E-01 0.0151 6.8E-01 -0.0295 2.3E-01 Alistipes_shahii UniRef90_D4IJK5 Cluster: N6-adenine-specific methylase 0.12 0.0256 4.2E-01 6.5E-01 0.1398 4.9E-02 -0.0078 6.8E-01 0.0351 5.6E-01 0.0419 2.9E-01 Alistipes_shahii UniRef90_D4IQQ3 Cluster: Arylsulfatase 0.12 0.0165 4.2E-01 6.5E-01 -0.0077 8.7E-01 -0.0048 6.9E-01 -0.0061 8.8E-01 -0.0169 5.1E-01 Alistipes_shahii UniRef90_D4IIJ5 Cluster: Penicillin-binding protein 1C 0.14 0.0228 4.2E-01 6.5E-01 0.0642 3.1E-01 -0.0043 8.0E-01 0.0688 2.0E-01 -0.0331 3.6E-01 Alistipes_shahii UniRef90_I3YHR0 Cluster: CTP synthase 0.21 0.0282 4.3E-01 6.6E-01 0.0409 6.1E-01 -0.0210 3.1E-01 0.0502 4.6E-01 -0.0129 7.7E-01 Alistipes_shahii UniRef90_D4IQH1 Cluster: Predicted phosphohydrolases 0.13 0.0192 4.3E-01 6.6E-01 0.0907 9.1E-02 0.0043 7.6E-01 0.0269 5.6E-01 0.0154 6.1E-01 Alistipes_shahii UniRef90_D4ILY6 Cluster: Peptidyl-prolyl cis-trans isomerase (Rotamase)-cyclophilin family 0.11 0.0168 4.3E-01 6.6E-01 0.0329 4.8E-01 0.0030 8.1E-01 0.0757 5.4E-02 0.0114 6.7E-01 Alistipes_shahii UniRef90_D4INR2 Cluster: Tetrahydrodipicolinate N-succinyltransferase 0.21 0.0414 4.3E-01 6.6E-01 0.0759 5.4E-01 -0.0120 6.9E-01 0.1510 1.3E-01 -0.0807 2.1E-01 Alistipes_shahii UniRef90_D4IJ85 Cluster: ABC-type branched-chain amino acid transport systems, ATPase 0.14 0.0248 4.3E-01 6.6E-01 0.0365 6.1E-01 -0.0072 7.0E-01 0.0830 1.6E-01 -0.0710 7.5E-02 component Alistipes_shahii UniRef90_D4IKY4 Cluster: Deoxyribose-phosphate aldolase 0.20 0.0343 4.3E-01 6.6E-01 0.0095 9.3E-01 -0.0364 1.5E-01 0.0654 4.3E-01 -0.0387 4.8E-01 Alistipes_shahii UniRef90_D4IMC8 Cluster: Fibronectin type-III domain-containing protein 0.14 0.0209 4.4E-01 6.6E-01 0.0848 1.6E-01 -0.0078 6.2E-01 0.0842 9.1E-02 -0.0022 9.5E-01 Alistipes_shahii UniRef90_D4IPQ3 Cluster: 4-hydroxy-tetrahydrodipicolinate reductase 0.17 0.0312 4.4E-01 6.6E-01 -0.0362 7.0E-01 -0.0247 3.0E-01 0.0180 8.2E-01 -0.1307 1.0E-02 Alistipes_shahii UniRef90_G5SRE3 Cluster: DUF4948 domain-containing protein 0.13 0.0133 4.4E-01 6.6E-01 0.0387 3.1E-01 -0.0019 8.5E-01 -0.0185 5.7E-01 -0.0292 1.8E-01 Alistipes_shahii UniRef90_I3YP72 Cluster: Riboflavin synthase, alpha subunit 0.18 0.0314 4.4E-01 6.6E-01 -0.0241 7.9E-01 -0.0060 8.0E-01 0.0113 8.8E-01 -0.0360 4.8E-01 Alistipes_shahii UniRef90_D4IQF0 Cluster: Phosphoribosylglycinamide formyltransferase 0.14 0.0272 4.5E-01 6.7E-01 0.0195 8.1E-01 0.0051 8.1E-01 -0.0114 8.7E-01 0.0032 9.4E-01 Alistipes_shahii UniRef90_D4INB0 Cluster: 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase 0.12 0.0236 4.5E-01 6.7E-01 0.1310 5.4E-02 -0.0098 5.9E-01 0.0387 5.0E-01 0.0539 1.7E-01 Alistipes_shahii UniRef90_R7JQ48 Cluster: DksA C4-type domain-containing protein 0.18 0.0396 4.5E-01 6.7E-01 0.1178 3.2E-01 -0.0190 5.3E-01 0.1418 1.4E-01 -0.0318 6.3E-01 Alistipes_shahii UniRef90_D4ILA7 Cluster: Beta-galactosidase 0.17 0.0278 4.5E-01 6.7E-01 0.1190 1.6E-01 -0.0112 6.0E-01 0.0759 2.8E-01 -0.0221 6.3E-01 Alistipes_shahii UniRef90_D4IP28 Cluster: Peptidylprolyl isomerase 0.15 0.0198 4.5E-01 6.8E-01 0.1048 7.6E-02 -0.0171 2.6E-01 -0.0008 9.9E-01 -0.0478 1.5E-01 Alistipes_shahii UniRef90_D4IKD2 Cluster: Transglutaminase-like enzymes, putative cysteine proteases 0.13 0.0181 4.6E-01 6.8E-01 0.1248 2.1E-02 0.0066 6.4E-01 0.1095 1.5E-02 0.0123 6.9E-01 Alistipes_shahii UniRef90_D4IP98 Cluster: Replication-associated recombination protein A 0.16 0.0197 4.6E-01 6.8E-01 0.0733 2.1E-01 -0.0055 7.2E-01 0.0272 5.9E-01 -0.0455 1.7E-01 Alistipes_shahii UniRef90_D4IME1 Cluster: Phosphopantetheinyl transferase component of siderophore 0.17 0.0394 4.6E-01 6.8E-01 -0.1268 2.9E-01 -0.0110 7.2E-01 0.0288 7.7E-01 -0.0331 6.2E-01 synthetase Alistipes_shahii UniRef90_D4IJ52 Cluster: Uronate isomerase 0.14 0.0178 4.6E-01 6.8E-01 0.0608 2.4E-01 -0.0046 7.4E-01 -0.0022 9.6E-01 0.0056 8.5E-01 Alistipes_shahii UniRef90_D4IJK3 Cluster: Outer membrane protein 0.16 0.0303 4.6E-01 6.8E-01 0.0453 6.3E-01 -0.0289 2.2E-01 0.0275 7.3E-01 -0.0606 2.4E-01 Alistipes_shahii UniRef90_D4IQF1 Cluster: Phosphoribosylformylglycinamidine cyclo-ligase 0.16 0.0205 4.6E-01 6.8E-01 0.0462 4.6E-01 -0.0157 3.4E-01 0.0996 5.5E-02 0.0113 7.5E-01 Alistipes_shahii UniRef90_R6VYW4 Cluster: Dihydroorotate dehydrogenase 0.15 0.0266 4.6E-01 6.8E-01 0.0816 3.1E-01 0.0205 3.3E-01 0.0502 4.6E-01 -0.0121 7.9E-01 Alistipes_shahii UniRef90_D4IK27 Cluster: D-3-phosphoglycerate dehydrogenase 0.21 0.0355 4.6E-01 6.8E-01 0.0640 5.6E-01 -0.0118 6.7E-01 0.1113 2.3E-01 -0.0314 6.0E-01 Alistipes_shahii UniRef90_D4IPB9 Cluster: Serine--tRNA ligase 0.13 0.0184 4.6E-01 6.8E-01 0.0537 3.3E-01 -0.0177 2.3E-01 -0.0128 7.9E-01 -0.0383 2.3E-01 Alistipes_shahii UniRef90_D4ILK8 Cluster: Ion-translocating oxidoreductase complex subunit D 0.14 0.0202 4.7E-01 6.8E-01 -0.0172 7.8E-01 -0.0018 9.1E-01 -0.0213 6.8E-01 0.0261 4.6E-01 50

Supplementary Data 3b UniRef90 Family Plasma TMAO Red meat Red meat Choline Choline Species Cluster Name Detection member ID Rate Effect P FDR Effect P Effect P Effect P Effect P Alistipes_shahii UniRef90_D4IN93 Cluster: Ribose-5-phosphate isomerase 0.16 0.0339 4.7E-01 6.8E-01 -0.0011 9.9E-01 0.0351 1.9E-01 0.0910 3.0E-01 -0.0321 5.8E-01 Alistipes_shahii UniRef90_D4IMH6 Cluster: Ornithine/acetylornithine aminotransferase 0.17 0.0260 4.8E-01 6.9E-01 0.0855 3.0E-01 0.0000 1.0E+00 0.1038 1.3E-01 -0.0696 1.3E-01 Alistipes_shahii UniRef90_D4INT5 Cluster: NADH dehydrogenase subunit L 0.11 0.0118 4.8E-01 6.9E-01 0.0685 6.3E-02 -0.0152 1.2E-01 0.0218 4.8E-01 -0.0160 4.4E-01 Alistipes_shahii UniRef90_D4IP83 Cluster: Transketolase 1 0.22 -0.0275 4.8E-01 6.9E-01 -0.0256 7.7E-01 -0.0212 3.4E-01 0.0786 2.8E-01 -0.0269 5.8E-01 Alistipes_shahii UniRef90_D4IN14 Cluster: Predicted hydrolases of HD superfamily 0.17 0.0373 4.8E-01 7.0E-01 -0.0086 9.4E-01 -0.0020 9.5E-01 -0.0866 3.9E-01 -0.0581 3.8E-01 Alistipes_shahii UniRef90_D4IJ63 Cluster: Clostripain family protease 0.15 -0.0206 4.8E-01 7.0E-01 0.0234 7.2E-01 -0.0211 2.1E-01 0.0317 5.6E-01 -0.0389 2.9E-01 Alistipes_shahii UniRef90_D4IIZ5 Cluster: Probable GTP-binding protein EngB 0.13 0.0235 4.8E-01 7.0E-01 0.0667 3.7E-01 -0.0320 1.0E-01 -0.0199 7.5E-01 -0.0336 4.2E-01 Alistipes_shahii UniRef90_D4ILR8 Cluster: Sigma-70 region 2 0.11 0.0375 4.8E-01 7.0E-01 0.0471 6.9E-01 -0.0177 5.7E-01 0.1101 2.7E-01 -0.0130 8.5E-01 Alistipes_shahii UniRef90_D4IJQ7 Cluster: Bacterial capsule synthesis protein PGA_cap 0.19 0.0400 4.9E-01 7.0E-01 0.0825 5.4E-01 -0.0162 6.3E-01 0.1853 8.8E-02 -0.0263 7.1E-01 Alistipes_shahii UniRef90_UPI0002D321D2 Cluster: tRNA (adenosine(37)-N6)-threonylcarbamoyltransferase complex 0.15 -0.0247 4.9E-01 7.0E-01 0.1326 1.0E-01 0.0085 6.9E-01 0.1095 1.1E-01 0.0262 5.7E-01 dimerization subunit type 1 TsaB Alistipes_shahii UniRef90_D4IL96 Cluster: Phosphate starvation-inducible protein PhoH, predicted ATPase 0.20 0.0262 5.0E-01 7.1E-01 0.0721 4.2E-01 -0.0083 7.1E-01 0.0610 4.1E-01 -0.0648 1.7E-01 Alistipes_shahii UniRef90_D4IK02 Cluster: 2,3-bisphosphoglycerate-dependent phosphoglycerate mutase 0.17 0.0344 5.0E-01 7.2E-01 -0.0437 7.1E-01 -0.0188 5.2E-01 0.0836 3.8E-01 -0.1557 1.3E-02 Alistipes_shahii UniRef90_D4IND6 Cluster: Glycosyltransferase 0.12 0.0149 5.0E-01 7.2E-01 0.0784 1.2E-01 -0.0069 6.0E-01 -0.0027 9.5E-01 0.0185 5.2E-01 Alistipes_shahii UniRef90_D4IJP2 Cluster: FAD synthase 0.12 0.0218 5.1E-01 7.2E-01 0.1103 1.4E-01 0.0330 8.2E-02 -0.0073 9.1E-01 0.0600 1.4E-01 Alistipes_shahii UniRef90_D4INZ4 Cluster: Response regulators consisting of a CheY-like receiver domain and 0.11 0.0155 5.1E-01 7.2E-01 0.0035 9.5E-01 -0.0071 6.0E-01 0.0237 5.9E-01 0.0179 5.4E-01 a winged-helix DNA-binding domain Alistipes_shahii UniRef90_I3YMD3 Cluster: Extracellular basic protease 0.20 0.0274 5.1E-01 7.2E-01 -0.1303 1.7E-01 -0.0386 1.1E-01 -0.0038 9.6E-01 0.0114 8.3E-01 Alistipes_shahii UniRef90_D4IJ14 Cluster: PPIase FKBP-type domain-containing protein 0.17 0.0212 5.1E-01 7.2E-01 0.0272 7.1E-01 -0.0322 8.3E-02 0.0333 5.8E-01 -0.0892 2.5E-02 Alistipes_shahii UniRef90_D4IP77 Cluster: Amidohydrolase 0.12 0.0191 5.1E-01 7.2E-01 -0.0499 4.5E-01 -0.0192 2.6E-01 -0.0242 6.7E-01 -0.0511 1.6E-01 Alistipes_shahii UniRef90_A0A015U8H2 Cluster: Lce1l protein 0.11 -0.0110 5.1E-01 7.2E-01 -0.0259 4.9E-01 -0.0117 2.5E-01 -0.0241 4.4E-01 -0.0444 4.1E-02 Alistipes_shahii UniRef90_D4IJ84 Cluster: Predicted Fe-S oxidoreductases 0.21 0.0345 5.2E-01 7.3E-01 -0.0280 8.2E-01 -0.0019 9.5E-01 0.0775 4.5E-01 -0.0667 3.2E-01 Alistipes_shahii UniRef90_D4IPY9 Cluster: Phosphoglycerol transferase and related proteins, alkaline 0.10 0.0095 5.2E-01 7.4E-01 0.0146 6.8E-01 -0.0063 4.6E-01 -0.0001 1.0E+00 0.0164 3.7E-01 phosphatase superfamily Alistipes_shahii UniRef90_D4IIQ9 Cluster: Dioxygenases related to 2-nitropropane dioxygenase 0.17 0.0223 5.3E-01 7.4E-01 0.1068 1.7E-01 0.0082 6.9E-01 0.0973 1.4E-01 -0.0078 8.6E-01 Alistipes_shahii UniRef90_D4IJS0 Cluster: Response regulator of the LytR/AlgR family 0.11 0.0162 5.3E-01 7.4E-01 0.0492 4.0E-01 -0.0174 2.5E-01 0.0069 8.9E-01 0.0126 7.0E-01 Alistipes_shahii UniRef90_I3YNF2 Cluster: Succinate dehydrogenase subunit A 0.24 0.0275 5.3E-01 7.4E-01 0.0236 8.2E-01 -0.0240 3.4E-01 0.1282 1.3E-01 -0.0327 5.5E-01 Alistipes_shahii UniRef90_D4ILI0 Cluster: M23 family peptidase 0.12 0.0119 5.4E-01 7.5E-01 0.0527 2.1E-01 0.0018 8.7E-01 0.0200 5.8E-01 -0.0095 7.0E-01 Alistipes_shahii UniRef90_D4ING2 Cluster: NAD kinase 0.13 0.0178 5.4E-01 7.5E-01 0.0182 7.8E-01 -0.0125 4.6E-01 0.0355 5.2E-01 -0.0132 7.2E-01 Alistipes_shahii UniRef90_D4IL51 Cluster: Cold-shock DNA-binding protein family 0.16 0.0332 5.4E-01 7.5E-01 0.0395 7.5E-01 -0.0366 2.5E-01 0.0988 3.4E-01 -0.0207 7.6E-01 Alistipes_shahii UniRef90_D4IJL1 Cluster: Predicted ATPase involved in cell division 0.15 0.0206 5.4E-01 7.5E-01 0.0342 6.6E-01 -0.0081 6.8E-01 0.1026 1.1E-01 -0.0178 6.8E-01 Alistipes_shahii UniRef90_D4IMF5 Cluster: Bacterial membrane protein YfhO 0.18 0.0179 5.4E-01 7.5E-01 0.0432 5.2E-01 -0.0229 1.8E-01 0.0618 2.7E-01 -0.0451 2.2E-01 Alistipes_shahii UniRef90_D4IIZ4 Cluster: Ribose-phosphate diphosphokinase 0.15 0.0163 5.5E-01 7.6E-01 -0.0338 5.7E-01 -0.0173 2.7E-01 -0.0104 8.4E-01 -0.0451 1.9E-01 Alistipes_shahii UniRef90_D4IK21 Cluster: Peroxiredoxin 0.11 0.0164 5.5E-01 7.6E-01 0.0469 4.4E-01 -0.0044 7.8E-01 0.0393 4.4E-01 0.0060 8.6E-01 Alistipes_shahii UniRef90_D4IKZ8 Cluster: Glucokinase 0.21 0.0309 5.5E-01 7.6E-01 0.0596 6.2E-01 -0.0295 3.2E-01 0.1781 7.1E-02 -0.0977 1.3E-01 Alistipes_shahii UniRef90_D4IND2 Cluster: 50S ribosomal protein L28 0.11 0.0239 5.5E-01 7.6E-01 0.0766 3.8E-01 -0.0292 2.2E-01 -0.0423 5.7E-01 0.0034 9.5E-01 Alistipes_shahii UniRef90_R7JLV4 Cluster: Threonine--tRNA ligase 0.21 0.0193 5.5E-01 7.6E-01 0.0486 5.1E-01 -0.0048 8.0E-01 0.0674 2.7E-01 -0.0190 6.4E-01 Alistipes_shahii UniRef90_D4IJR1 Cluster: Pyrimidine reductase, riboflavin biosynthesis 0.12 0.0176 5.5E-01 7.6E-01 0.1012 1.3E-01 0.0089 6.0E-01 0.0221 6.9E-01 0.0161 6.7E-01 Alistipes_shahii UniRef90_D4IQH2 Cluster: Predicted sugar phosphatases of the HAD superfamily 0.13 0.0158 5.6E-01 7.6E-01 0.0541 3.6E-01 0.0183 2.4E-01 -0.0335 5.1E-01 -0.0185 5.8E-01 Alistipes_shahii UniRef90_I3YNT7 Cluster: Response regulator containing CheY-like receiver, AAA-type 0.16 0.0134 5.6E-01 7.6E-01 0.0047 9.3E-01 -0.0182 1.8E-01 0.0380 3.8E-01 -0.0442 1.3E-01 ATPase, and DNA-binding domains Alistipes_shahii UniRef90_R6Y151 Cluster: NADH-quinone oxidoreductase subunit D 0.14 0.0122 5.6E-01 7.7E-01 0.0915 5.1E-02 -0.0161 1.9E-01 0.0630 1.1E-01 0.0014 9.6E-01 Alistipes_shahii UniRef90_D4ILA2 Cluster: Glycerol-3-phosphate acyltransferase 0.13 0.0174 5.6E-01 7.7E-01 0.0308 6.5E-01 0.0035 8.4E-01 0.0926 1.0E-01 0.0420 2.6E-01 Alistipes_shahii UniRef90_D4IJ51 Cluster: Sugar kinases, ribokinase family 0.15 0.0185 5.6E-01 7.7E-01 0.1249 8.6E-02 -0.0012 9.5E-01 0.0854 1.6E-01 -0.0319 4.3E-01 Alistipes_shahii UniRef90_D4ILA3 Cluster: Long-chain acyl-CoA synthetases (AMP-forming) 0.19 0.0179 5.7E-01 7.7E-01 0.0618 3.9E-01 0.0006 9.7E-01 0.0033 9.6E-01 -0.0175 6.6E-01 Alistipes_shahii UniRef90_D4IKA4 Cluster: Acetyltransferases, including N-acetylases of ribosomal proteins 0.14 0.0197 5.7E-01 7.7E-01 -0.0975 2.1E-01 -0.0172 4.0E-01 -0.0065 9.2E-01 -0.0732 9.9E-02 Alistipes_shahii UniRef90_D4IJ69 Cluster: Electron transfer flavoprotein, alpha subunit 0.17 0.0179 5.7E-01 7.7E-01 0.0328 6.5E-01 -0.0174 3.4E-01 0.1139 5.9E-02 0.0146 7.1E-01 Alistipes_shahii UniRef90_D4IQ63 Cluster: 2-dehydro-3-deoxyphosphooctonate aldolase 0.10 0.0130 5.8E-01 7.7E-01 0.0791 1.2E-01 -0.0158 2.5E-01 0.0121 7.8E-01 -0.0507 8.9E-02 Alistipes_shahii UniRef90_D4IM00 Cluster: Peptidyl-tRNA hydrolase 0.11 0.0117 5.8E-01 7.7E-01 -0.0528 2.5E-01 0.0003 9.8E-01 -0.0233 5.4E-01 -0.0171 5.2E-01 Alistipes_shahii UniRef90_D4IL28 Cluster: FecR domain-containing protein 0.18 -0.0268 5.8E-01 7.8E-01 0.0102 9.3E-01 -0.0233 4.1E-01 0.1287 1.6E-01 0.0619 3.0E-01 Alistipes_shahii UniRef90_D4IM21 Cluster: Endothelin-converting enzyme. Metallo peptidase. MEROPS family 0.16 0.0118 5.9E-01 7.8E-01 0.0607 2.1E-01 -0.0219 8.6E-02 0.0189 6.4E-01 -0.0153 5.8E-01 M13 Alistipes_shahii UniRef90_D4IL03 Cluster: Dipeptidyl aminopeptidases/acylaminoacyl-peptidases 0.11 -0.0076 5.9E-01 7.8E-01 0.0119 7.1E-01 -0.0008 9.2E-01 0.0220 4.1E-01 -0.0075 6.7E-01 Alistipes_shahii UniRef90_D4IPU2 Cluster: 3-isopropylmalate dehydratase small subunit 0.11 -0.0153 5.9E-01 7.8E-01 0.0127 8.4E-01 0.0017 9.2E-01 0.0934 6.9E-02 0.0017 9.6E-01 Alistipes_shahii UniRef90_D4IKZ9 Cluster: Geranylgeranyl pyrophosphate synthase 0.15 0.0168 5.9E-01 7.9E-01 0.1037 1.4E-01 -0.0150 4.1E-01 0.0490 4.0E-01 0.0048 9.0E-01 Alistipes_shahii UniRef90_D4INA6 Cluster: Purine nucleoside phosphorylase 0.19 0.0274 5.9E-01 7.9E-01 0.1496 1.9E-01 0.0255 3.9E-01 0.1331 1.7E-01 0.0168 7.9E-01 Alistipes_shahii UniRef90_D4IJ08 Cluster: Beta-glucosidase-related glycosidases 0.17 0.0162 5.9E-01 7.9E-01 0.0330 6.3E-01 -0.0081 6.4E-01 0.0255 6.5E-01 0.0307 4.2E-01 Alistipes_shahii UniRef90_D4IJ43 Cluster: DNA topoisomerase (ATP-hydrolyzing) 0.19 0.0124 6.0E-01 7.9E-01 0.0496 3.6E-01 -0.0129 3.4E-01 0.0217 6.3E-01 0.0100 7.3E-01 Alistipes_shahii UniRef90_D4ILV6 Cluster: Cytidylate kinase 0.10 0.0107 6.0E-01 7.9E-01 0.0068 8.8E-01 0.0003 9.8E-01 -0.0199 6.0E-01 -0.0324 2.0E-01 Alistipes_shahii UniRef90_D4INH0 Cluster: Predicted hydrolases or acyltransferases (Alpha/beta hydrolase 0.10 0.0121 6.0E-01 7.9E-01 0.0199 6.9E-01 -0.0179 1.8E-01 -0.0134 7.5E-01 -0.0208 4.7E-01 superfamily) Alistipes_shahii UniRef90_I3YP05 Cluster: Isoleucine--tRNA ligase 0.18 0.0109 6.0E-01 7.9E-01 0.0070 8.8E-01 -0.0195 1.1E-01 -0.0413 3.0E-01 -0.0434 1.0E-01 Alistipes_shahii UniRef90_D4IL19 Cluster: D-mannonate oxidoreductase 0.13 0.0229 6.1E-01 7.9E-01 0.0799 4.3E-01 0.0336 1.9E-01 0.0890 2.9E-01 0.0116 8.3E-01 Alistipes_shahii UniRef90_D4IJR9 Cluster: DUF4890 domain-containing protein 0.16 -0.0329 6.1E-01 7.9E-01 -0.1588 2.7E-01 -0.0274 4.5E-01 -0.0069 9.5E-01 -0.2240 4.2E-03 Alistipes_shahii UniRef90_D4IKU0 Cluster: Lipopolysaccharide kinase (Kdo/WaaP) family 0.10 0.0138 6.1E-01 7.9E-01 -0.0049 9.3E-01 -0.0195 2.1E-01 -0.0601 2.3E-01 -0.0124 7.1E-01 Alistipes_shahii UniRef90_D4IQD9 Cluster: Outer membrane receptor proteins, mostly Fe transport 0.12 -0.0083 6.1E-01 7.9E-01 0.0036 9.2E-01 0.0059 5.3E-01 -0.0244 4.1E-01 -0.0261 2.0E-01 Alistipes_shahii UniRef90_D4IIN9 Cluster: Acyl-[acyl-carrier-protein]--UDP-N-acetylglucosamine O- 0.16 0.0171 6.2E-01 8.0E-01 0.0429 5.7E-01 0.0026 9.0E-01 0.0984 1.2E-01 0.0117 7.9E-01 acyltransferase Alistipes_shahii UniRef90_D4ILG2 Cluster: UPF0102 protein AL1_13060 0.11 0.0260 6.2E-01 8.0E-01 -0.1615 1.7E-01 -0.0006 9.8E-01 -0.0375 7.0E-01 -0.0503 4.4E-01 Alistipes_shahii UniRef90_D4INC5 Cluster: Peptidylprolyl isomerase 0.22 0.0222 6.2E-01 8.0E-01 0.0587 5.7E-01 -0.0220 3.9E-01 0.1108 2.0E-01 -0.0359 5.2E-01 Alistipes_shahii UniRef90_D4IND5 Cluster: Glycosyltransferase 0.12 0.0102 6.2E-01 8.0E-01 0.0292 5.1E-01 0.0066 5.8E-01 -0.0239 5.2E-01 -0.0165 5.2E-01 Alistipes_shahii UniRef90_D4IMS0 Cluster: Long-chain fatty acid transport protein 0.21 0.0286 6.2E-01 8.0E-01 0.0704 6.0E-01 -0.0070 8.3E-01 0.0287 7.9E-01 -0.1288 6.6E-02 Alistipes_shahii UniRef90_D4IMI2 Cluster: Predicted metal-dependent phosphoesterases (PHP family) 0.13 0.0147 6.2E-01 8.0E-01 0.0694 3.0E-01 0.0048 7.8E-01 0.0574 3.1E-01 -0.0436 2.3E-01 Alistipes_shahii UniRef90_D4IJI2 Cluster: dTDP-4-dehydrorhamnose reductase 0.12 -0.0140 6.2E-01 8.0E-01 0.0489 4.3E-01 0.0045 7.9E-01 0.0481 3.6E-01 0.0038 9.2E-01 Alistipes_shahii UniRef90_D4IJJ5 Cluster: Peptide methionine sulfoxide reductase MsrA 0.18 0.0270 6.2E-01 8.0E-01 0.0787 5.3E-01 -0.0337 2.9E-01 0.0872 4.0E-01 -0.0726 2.9E-01 Alistipes_shahii UniRef90_D4ILJ3 Cluster: Heat shock protein 0.18 0.0342 6.2E-01 8.0E-01 0.0517 7.5E-01 0.0149 7.1E-01 -0.1273 3.4E-01 -0.0767 3.7E-01 Alistipes_shahii UniRef90_D4IK09 Cluster: Homoserine dehydrogenase 0.14 0.0105 6.2E-01 8.0E-01 0.0731 1.2E-01 -0.0090 4.7E-01 0.0550 1.7E-01 -0.0080 7.7E-01 Alistipes_shahii UniRef90_I3YNR0 Cluster: Peptidase T 0.15 0.0099 6.3E-01 8.0E-01 0.0067 8.8E-01 -0.0085 4.8E-01 0.0074 8.4E-01 -0.0266 3.0E-01 Alistipes_shahii UniRef90_D4IKY6 Cluster: C-terminal peptidase (Prc) 0.16 0.0108 6.3E-01 8.1E-01 0.0367 4.6E-01 0.0003 9.8E-01 0.0785 6.0E-02 -0.0074 8.0E-01 Alistipes_shahii UniRef90_D4IMB1 Cluster: Exopolyphosphatase-related proteins 0.18 0.0189 6.3E-01 8.1E-01 0.1628 6.5E-02 -0.0061 7.9E-01 0.0124 8.7E-01 0.0375 4.5E-01 Alistipes_shahii UniRef90_I3YHR7 Cluster: Phosphate acetyltransferase 0.20 0.0209 6.4E-01 8.1E-01 0.0761 4.7E-01 -0.0156 5.5E-01 0.0279 7.5E-01 0.0164 7.7E-01 Alistipes_shahii UniRef90_D4IPZ4 Cluster: Glycosyltransferases involved in cell wall biogenesis 0.15 0.0136 6.4E-01 8.1E-01 -0.0566 3.9E-01 -0.0192 2.5E-01 0.0311 5.7E-01 -0.0413 2.6E-01 Alistipes_shahii UniRef90_D4IN12 Cluster: rRNA methylase, putative, group 3 0.13 0.0113 6.4E-01 8.1E-01 0.1336 1.3E-02 0.0120 3.9E-01 0.0143 7.6E-01 -0.0007 9.8E-01 Alistipes_shahii UniRef90_D4ILY7 Cluster: Polysacc_synt_C domain-containing protein 0.16 0.0126 6.4E-01 8.1E-01 0.0655 2.8E-01 -0.0042 7.9E-01 0.0370 4.7E-01 0.0088 7.9E-01 Alistipes_shahii UniRef90_D4IP66 Cluster: DNA polymerase III, delta subunit 0.12 0.0109 6.4E-01 8.1E-01 0.0670 2.0E-01 -0.0033 8.1E-01 0.0223 6.1E-01 0.0060 8.4E-01 Alistipes_shahii UniRef90_D4INJ3 Cluster: Acyltransferase 0.16 0.0163 6.4E-01 8.1E-01 0.2065 1.1E-02 -0.0021 9.2E-01 0.1020 1.3E-01 -0.0185 6.7E-01 Alistipes_shahii UniRef90_D4INK4 Cluster: 5'-nucleotidase/2',3'-cyclic phosphodiesterase and related 0.13 0.0098 6.4E-01 8.1E-01 0.0683 1.4E-01 -0.0017 8.9E-01 0.0493 2.2E-01 -0.0224 4.1E-01 Alistipes_shahii UniRef90_D4IL63 Cluster:esterases Iron-regulated ABC transporter ATPase subunit SufC 0.14 0.0139 6.4E-01 8.1E-01 0.0496 4.6E-01 0.0215 2.2E-01 0.0498 3.8E-01 -0.0058 8.8E-01 Alistipes_shahii UniRef90_I3YQ42 Cluster: DNA repair protein RadA 0.15 -0.0101 6.5E-01 8.1E-01 0.0101 8.5E-01 -0.0246 8.3E-02 -0.0195 6.7E-01 0.0078 8.0E-01 Alistipes_shahii UniRef90_D4IJJ2 Cluster: Urocanate hydratase 0.20 0.0142 6.5E-01 8.2E-01 0.0609 4.0E-01 0.0114 5.3E-01 0.1313 2.6E-02 0.0001 1.0E+00 Alistipes_shahii UniRef90_D4INJ0 Cluster: Glycosyltransferases involved in cell wall biogenesis 0.10 0.0128 6.5E-01 8.2E-01 0.0660 2.9E-01 -0.0120 4.7E-01 0.0728 1.6E-01 -0.0493 1.6E-01 Alistipes_shahii UniRef90_I3YMY3 Cluster: 50S ribosomal protein L10 0.21 0.0272 6.5E-01 8.1E-01 0.0836 5.4E-01 -0.0189 5.9E-01 0.0392 7.3E-01 -0.1054 1.6E-01 Alistipes_shahii UniRef90_D4IKC3 Cluster: Acetolactate synthase 0.12 -0.0091 6.5E-01 8.1E-01 0.0556 2.0E-01 -0.0092 4.4E-01 0.0284 4.4E-01 0.0287 2.6E-01 Alistipes_shahii UniRef90_F9Z5Q9 Cluster: HTH luxR-type domain-containing protein 0.14 -0.0035 6.5E-01 8.1E-01 -0.0111 5.0E-01 -0.0012 7.9E-01 -0.0091 5.2E-01 -0.0086 3.7E-01 51

Supplementary Data 3b UniRef90 Family Plasma TMAO Red meat Red meat Choline Choline Species Cluster Name Detection member ID Rate Effect P FDR Effect P Effect P Effect P Effect P Alistipes_shahii UniRef90_D4IQG9 Cluster: G-3-P permease 0.18 0.0156 6.5E-01 8.2E-01 0.0039 9.6E-01 -0.0110 5.8E-01 0.0113 8.6E-01 0.0201 6.4E-01 Alistipes_shahii UniRef90_I3YJS6 Cluster: NADH-quinone oxidoreductase subunit H 0.11 -0.0071 6.6E-01 8.2E-01 -0.0058 8.7E-01 0.0030 7.5E-01 0.0508 8.2E-02 0.0165 4.1E-01 Alistipes_shahii UniRef90_I3YHI6 Cluster: Biopolymer transport protein 0.11 -0.0170 6.6E-01 8.3E-01 0.0530 5.5E-01 0.0084 7.1E-01 0.0260 7.3E-01 -0.0275 5.8E-01 Alistipes_shahii UniRef90_D4IK10 Cluster: Fib_succ_major domain-containing protein 0.12 0.0110 6.6E-01 8.2E-01 0.0137 8.1E-01 -0.0157 2.9E-01 0.0641 1.8E-01 0.0164 6.1E-01 Alistipes_shahii UniRef90_R5V616 Cluster: MoxR-like ATPases 0.15 0.0121 6.7E-01 8.2E-01 0.0749 2.3E-01 -0.0241 1.4E-01 0.0226 6.7E-01 0.0091 7.9E-01 Alistipes_shahii UniRef90_D4IMG5 Cluster: 5'-nucleotidase SurE 0.11 0.0118 6.7E-01 8.3E-01 -0.0633 3.2E-01 0.0056 7.2E-01 0.0707 1.8E-01 0.0634 6.1E-02 Alistipes_shahii UniRef90_D4IN10 Cluster: Glycerol-3-phosphate transporter 0.17 0.0153 6.7E-01 8.3E-01 0.0513 5.3E-01 -0.0123 5.5E-01 -0.0411 5.5E-01 -0.0004 9.9E-01 Alistipes_shahii UniRef90_I3YIT7 Cluster: CobQ/CobB/MinD/ParA nucleotide binding domain protein 0.12 0.0098 6.7E-01 8.3E-01 0.0405 4.2E-01 -0.0191 1.6E-01 0.0088 8.4E-01 0.0048 8.7E-01 Alistipes_shahii UniRef90_D4IPZ1 Cluster: Endonuclease/Exonuclease/phosphatase family protein 0.18 0.0189 6.7E-01 8.3E-01 -0.0025 9.8E-01 -0.0236 3.6E-01 0.0085 9.2E-01 -0.1011 6.7E-02 Alistipes_shahii UniRef90_D4ILY8 Cluster: 3-deoxy-D-manno-octulosonate 8-phosphate phosphatase, YrbI 0.16 0.0170 6.7E-01 8.3E-01 0.0858 3.4E-01 0.0066 7.8E-01 0.0690 3.6E-01 -0.0237 6.4E-01 family Alistipes_shahii UniRef90_D4IQS7 Cluster: Acetyl-CoA synthetase 0.16 0.0105 6.8E-01 8.3E-01 0.0573 3.1E-01 0.0012 9.3E-01 0.0605 2.0E-01 -0.0010 9.8E-01 Alistipes_shahii UniRef90_D4IQP9 Cluster: Predicted glycosyltransferases 0.11 0.0127 6.8E-01 8.3E-01 -0.0374 5.9E-01 -0.0021 9.0E-01 0.0952 1.0E-01 -0.0649 8.7E-02 Alistipes_shahii UniRef90_I3YLU2 Cluster: Ribosomal large subunit pseudouridine synthase D 0.20 0.0222 6.8E-01 8.3E-01 -0.0306 8.1E-01 -0.0540 8.1E-02 -0.0410 6.9E-01 -0.1414 3.3E-02 Alistipes_shahii UniRef90_D4IKX4 Cluster: Alpha-amylase/alpha-mannosidase 0.20 0.0166 6.8E-01 8.3E-01 0.0907 3.2E-01 0.0017 9.4E-01 0.0275 7.2E-01 -0.0150 7.6E-01 Alistipes_shahii UniRef90_D4IJP1 Cluster: ABC-type branched-chain amino acid transport systems, 0.19 0.0153 6.8E-01 8.3E-01 0.0652 4.4E-01 0.0000 1.0E+00 0.0341 6.3E-01 0.0177 7.0E-01 periplasmic component Alistipes_shahii UniRef90_D4IL01 Cluster: Uncharacterized conserved protein 0.14 -0.0111 6.8E-01 8.3E-01 0.0127 8.3E-01 -0.0087 5.8E-01 -0.0012 9.8E-01 -0.0200 5.5E-01 Alistipes_shahii UniRef90_D4ILS4 Cluster: Methyltransferase 0.14 -0.0142 6.8E-01 8.3E-01 0.1040 1.8E-01 0.0156 4.4E-01 0.1024 1.1E-01 -0.0394 3.6E-01 Alistipes_shahii UniRef90_D4ILF7 Cluster: NTP pyrophosphohydrolases including oxidative damage repair 0.11 0.0124 6.8E-01 8.4E-01 -0.0284 6.8E-01 0.0238 1.7E-01 0.0836 1.5E-01 0.0108 7.7E-01 enzymes Alistipes_shahii UniRef90_R6VD82 Cluster: Holliday junction ATP-dependent DNA helicase RuvB 0.16 0.0112 6.8E-01 8.3E-01 0.0713 2.5E-01 -0.0044 7.8E-01 0.0276 5.9E-01 -0.0698 4.3E-02 Alistipes_shahii UniRef90_D4INW5 Cluster: Predicted Na+-dependent transporter 0.13 0.0128 6.9E-01 8.3E-01 0.0518 4.7E-01 0.0150 4.1E-01 -0.0215 7.1E-01 0.0045 9.1E-01 Alistipes_shahii UniRef90_D4IKB4 Cluster: Highly conserved protein containing a thioredoxin domain 0.16 0.0154 6.9E-01 8.4E-01 0.1607 6.5E-02 0.0214 3.4E-01 0.1124 1.2E-01 -0.0276 5.7E-01 Alistipes_shahii UniRef90_D4ILU2 Cluster: Predicted dehydrogenases and related proteins 0.17 0.0114 6.9E-01 8.4E-01 0.0555 3.9E-01 -0.0086 6.1E-01 0.0926 8.4E-02 0.0280 4.4E-01 Alistipes_shahii UniRef90_D4IJP5 Cluster: Nitroreductase 0.11 0.0157 6.9E-01 8.4E-01 -0.0350 6.9E-01 0.0177 4.5E-01 0.0259 7.3E-01 0.0684 1.7E-01 Alistipes_shahii UniRef90_D4IJ32 Cluster: 1-deoxy-D-xylulose 5-phosphate reductoisomerase 0.16 0.0133 7.0E-01 8.4E-01 0.0691 3.7E-01 0.0030 8.8E-01 0.0537 4.0E-01 0.0219 6.1E-01 Alistipes_shahii UniRef90_D4IMG7 Cluster: Response regulator containing a CheY-like receiver domain and an 0.13 0.0139 7.0E-01 8.5E-01 0.0046 9.5E-01 -0.0047 8.2E-01 0.0748 2.6E-01 -0.0339 4.5E-01 HTH DNA-binding domain Alistipes_shahii UniRef90_R6WXR3 Cluster: Lysine--tRNA ligase 0.20 0.0122 7.0E-01 8.5E-01 0.1328 6.5E-02 0.0075 6.8E-01 0.0804 1.8E-01 -0.0017 9.7E-01 Alistipes_shahii UniRef90_D4IQT9 Cluster: Fe2+-dicitrate sensor, membrane component 0.14 0.0147 7.0E-01 8.5E-01 0.0171 8.5E-01 0.0243 2.8E-01 0.0677 3.6E-01 -0.0080 8.7E-01 Alistipes_shahii UniRef90_D4IMC2 Cluster: Esterase/lipase 0.14 0.0122 7.0E-01 8.5E-01 0.0918 2.0E-01 -0.0177 3.4E-01 0.0435 4.6E-01 0.0037 9.3E-01 Alistipes_shahii UniRef90_R6VEA5 Cluster: Thymidine kinase 0.12 0.0098 7.1E-01 8.5E-01 0.0190 7.4E-01 -0.0022 8.9E-01 0.0460 3.4E-01 -0.0116 7.2E-01 Alistipes_shahii UniRef90_D4IP41 Cluster: Thioredoxin 0.14 -0.0113 7.1E-01 8.5E-01 0.0302 6.6E-01 -0.0017 9.3E-01 0.0466 4.1E-01 0.0141 7.1E-01 Alistipes_shahii UniRef90_D4IP36 Cluster: Aspartate/tyrosine/aromatic aminotransferase 0.17 0.0139 7.2E-01 8.6E-01 0.0385 6.6E-01 -0.0419 5.8E-02 0.0041 9.5E-01 -0.0676 1.6E-01 Alistipes_shahii UniRef90_D4ILP1 Cluster: 7-carboxy-7-deazaguanine synthase 0.11 -0.0099 7.2E-01 8.6E-01 -0.0440 4.7E-01 -0.0049 7.6E-01 0.0537 2.9E-01 -0.0108 7.5E-01 Alistipes_shahii UniRef90_D4IPW7 Cluster: Sodium/proton antiporter, NhaD family (TC 2.A.62) 0.17 0.0119 7.2E-01 8.6E-01 0.0445 5.5E-01 -0.0289 1.3E-01 0.0818 1.9E-01 -0.0823 4.3E-02 Alistipes_shahii UniRef90_D4IQE8 Cluster: Bifunctional protein FolD 0.15 -0.0122 7.2E-01 8.6E-01 0.1183 1.3E-01 -0.0020 9.2E-01 0.0991 1.3E-01 -0.0552 1.9E-01 Alistipes_shahii UniRef90_P70882 Cluster: Tetracycline resistance protein TetQ 0.20 0.0083 7.2E-01 8.6E-01 0.0401 4.5E-01 0.0011 9.4E-01 0.0236 6.0E-01 -0.0173 5.5E-01 Alistipes_shahii UniRef90_D4IJQ3 Cluster: C-terminal peptidase (Prc) 0.17 -0.0116 7.2E-01 8.6E-01 0.0439 5.5E-01 -0.0060 7.5E-01 0.0844 1.7E-01 -0.0391 3.4E-01 Alistipes_shahii UniRef90_D4IK03 Cluster: Lactate dehydrogenase and related dehydrogenases 0.15 0.0098 7.3E-01 8.6E-01 0.0334 6.1E-01 -0.0082 6.3E-01 0.0539 3.2E-01 -0.0047 9.0E-01 Alistipes_shahii UniRef90_I3YM08 Cluster: Peptide chain release factor 1 0.16 0.0074 7.3E-01 8.6E-01 0.0704 1.4E-01 -0.0038 7.6E-01 0.0669 9.1E-02 -0.0274 3.0E-01 Alistipes_shahii UniRef90_D4IQ77 Cluster: N-acetylmuramic acid 6-phosphate etherase 0.17 0.0141 7.3E-01 8.6E-01 -0.0329 7.2E-01 -0.0116 6.2E-01 0.0682 3.7E-01 -0.0174 7.3E-01 Alistipes_shahii UniRef90_D4IPQ2 Cluster: tRNA pseudouridine synthase A 0.15 0.0113 7.3E-01 8.6E-01 0.0662 3.6E-01 0.0112 5.6E-01 0.0952 1.2E-01 -0.0620 1.3E-01 Alistipes_shahii UniRef90_D4ILW0 Cluster: Histidine kinase-, DNA gyrase B-, and HSP90-like ATPase 0.10 -0.0047 7.4E-01 8.7E-01 0.0167 6.3E-01 -0.0063 4.9E-01 0.0201 4.9E-01 0.0143 4.7E-01 Alistipes_shahii UniRef90_I3YLI1 Cluster: Haloacid dehalogenase-like hydrolase 0.18 -0.0131 7.4E-01 8.7E-01 0.0051 9.6E-01 -0.0246 2.8E-01 -0.0168 8.2E-01 -0.0427 3.8E-01 Alistipes_shahii UniRef90_D4INB8 Cluster: FOG: PKD repeat 0.12 0.0180 7.4E-01 8.7E-01 -0.0360 7.7E-01 0.0088 7.8E-01 -0.0395 7.0E-01 -0.0267 6.9E-01 Alistipes_shahii UniRef90_G5SRE5 Cluster: Putative transmembrane protein 0.14 0.0065 7.4E-01 8.7E-01 -0.0005 9.9E-01 -0.0083 4.7E-01 -0.0467 2.0E-01 -0.0263 2.9E-01 Alistipes_shahii UniRef90_D4IIP1 Cluster: Energy transducer TonB 0.14 0.0113 7.5E-01 8.8E-01 0.0491 5.3E-01 0.0227 2.6E-01 0.1491 2.1E-02 0.0466 2.8E-01 Alistipes_shahii UniRef90_R5UH24 Cluster: Zinc transporter ZupT 0.11 -0.0083 7.5E-01 8.8E-01 0.0083 8.9E-01 0.0001 1.0E+00 -0.0017 9.7E-01 -0.0197 5.4E-01 Alistipes_shahii UniRef90_D4IMF6 Cluster: Geranylgeranyl pyrophosphate synthase 0.17 -0.0128 7.5E-01 8.8E-01 0.1242 1.8E-01 0.0106 6.4E-01 0.0286 7.0E-01 -0.0363 4.6E-01 Alistipes_shahii UniRef90_D4IJD0 Cluster: Methylmalonyl-CoA mutase metallochaperone MeaB 0.16 0.0097 7.5E-01 8.8E-01 0.1091 1.1E-01 0.0067 7.1E-01 0.1164 4.3E-02 0.0397 3.0E-01 Alistipes_shahii UniRef90_D4ILA0 Cluster: Catalase 0.14 0.0082 7.5E-01 8.8E-01 -0.0328 5.8E-01 -0.0059 6.9E-01 -0.0111 8.2E-01 -0.0589 6.6E-02 Alistipes_shahii UniRef90_R6XXM7 Cluster: Oligopeptide transporter, OPT family 0.19 0.0089 7.5E-01 8.8E-01 0.0282 6.6E-01 -0.0164 3.2E-01 0.0549 3.1E-01 0.0228 5.2E-01 Alistipes_shahii UniRef90_D4IIP8 Cluster: Predicted dehydrogenases and related proteins 0.22 0.0167 7.5E-01 8.8E-01 0.0585 6.3E-01 0.0123 6.9E-01 -0.0079 9.4E-01 -0.0352 5.9E-01 Alistipes_shahii UniRef90_D4IJH3 Cluster: Glutamyl-tRNA amidotransferase 0.12 -0.0116 7.5E-01 8.8E-01 0.1263 1.3E-01 0.0155 4.7E-01 0.0991 1.6E-01 -0.0254 5.9E-01 Alistipes_shahii UniRef90_D4IQA4 Cluster: Mismatch repair ATPase (MutS family) 0.13 0.0084 7.5E-01 8.8E-01 0.0783 1.9E-01 -0.0118 4.5E-01 0.0905 7.1E-02 -0.0557 9.5E-02 Alistipes_shahii UniRef90_D4IL64 Cluster: ABC-type transport system involved in Fe-S cluster assembly, 0.15 0.0139 7.5E-01 8.8E-01 -0.0008 9.9E-01 -0.0246 3.5E-01 0.0255 7.7E-01 0.0115 8.4E-01 permease component Alistipes_shahii UniRef90_D4IPX3 Cluster: Signal recognition particle protein 0.16 0.0089 7.6E-01 8.8E-01 0.0815 2.0E-01 -0.0350 3.6E-02 0.0570 2.8E-01 -0.0232 5.2E-01 Alistipes_shahii UniRef90_D4IMH5 Cluster: N-acetylornithine carbamoyltransferase 0.20 0.0151 7.6E-01 8.8E-01 -0.0408 7.2E-01 0.0002 1.0E+00 0.0951 3.0E-01 -0.0745 2.2E-01 Alistipes_shahii UniRef90_I3YR67 Cluster: UPF0365 protein ALIPUT_00407 0.24 0.0176 7.6E-01 8.8E-01 0.1138 3.9E-01 -0.0161 6.2E-01 0.1949 7.5E-02 -0.0014 9.8E-01 Alistipes_shahii UniRef90_D4IQH0 Cluster: Glycerol dehydrogenase and related enzymes 0.12 0.0075 7.6E-01 8.8E-01 0.0317 5.7E-01 -0.0025 8.6E-01 0.0546 2.4E-01 0.0080 8.0E-01 Alistipes_shahii UniRef90_D4INX7 Cluster: Putative phospholipid ABC transporter permease protein MlaE 0.13 -0.0084 7.6E-01 8.8E-01 0.1170 5.2E-02 0.0032 8.4E-01 0.0065 9.0E-01 0.0030 9.3E-01 Alistipes_shahii UniRef90_D4IQB1 Cluster: PCMD domain-containing protein 0.15 0.0087 7.6E-01 8.8E-01 0.0435 5.0E-01 0.0012 9.4E-01 0.0088 8.7E-01 -0.0465 1.9E-01 Alistipes_shahii UniRef90_D4INC9 Cluster: Erythronate-4-phosphate dehydrogenase 0.15 -0.0116 7.6E-01 8.8E-01 0.0377 6.6E-01 -0.0322 1.5E-01 0.0865 2.3E-01 -0.0560 2.4E-01 Alistipes_shahii UniRef90_D4IKW2 Cluster: Na+/H+-dicarboxylate symporters 0.15 0.0096 7.6E-01 8.8E-01 0.0585 4.2E-01 0.0067 7.1E-01 0.0622 3.0E-01 0.0340 3.8E-01 Alistipes_shahii UniRef90_D4IP44 Cluster: RND family efflux transporter, MFP subunit 0.16 -0.0102 7.6E-01 8.8E-01 0.0481 5.2E-01 0.0017 9.3E-01 0.0915 1.5E-01 -0.0182 6.7E-01 Alistipes_shahii UniRef90_I3YPV3 Cluster: GTPase Era 0.13 0.0064 7.7E-01 8.8E-01 0.0625 1.9E-01 -0.0135 2.9E-01 0.0269 5.1E-01 -0.0174 5.2E-01 Alistipes_shahii UniRef90_D4IQ76 Cluster: Predicted N-acetylglucosamine kinase 0.15 0.0107 7.7E-01 8.8E-01 0.0747 3.5E-01 0.0037 8.6E-01 0.1193 7.6E-02 -0.0266 5.5E-01 Alistipes_shahii UniRef90_I3YKW5 Cluster: UDP-N-acetylglucosamine 1-carboxyvinyltransferase 0.17 -0.0086 7.7E-01 8.8E-01 0.0291 6.5E-01 -0.0263 1.2E-01 -0.0076 8.9E-01 -0.0373 3.0E-01 Alistipes_shahii UniRef90_D4IMC6 Cluster: Cytidine deaminase 0.17 0.0140 7.7E-01 8.8E-01 0.1514 1.6E-01 -0.0154 5.8E-01 0.2078 2.1E-02 -0.0239 6.9E-01 Alistipes_shahii UniRef90_D4ILI4 Cluster: 3-phosphoshikimate 1-carboxyvinyltransferase 0.21 0.0189 7.7E-01 8.8E-01 0.0109 9.4E-01 -0.0147 6.9E-01 0.0157 9.0E-01 -0.1212 1.3E-01 Alistipes_shahii UniRef90_D4IIK4 Cluster: Polysaccharide lyase family 8, N terminal alpha-helical 0.10 0.0038 7.7E-01 8.8E-01 0.0123 6.7E-01 -0.0131 8.7E-02 0.0349 1.6E-01 0.0014 9.3E-01 domain./Polysaccharide lyase family 8, super-sandwich domain Alistipes_shahii UniRef90_D4ILY9 Cluster: ComEC/Rec2-related protein 0.11 -0.0098 7.7E-01 8.8E-01 0.0393 6.1E-01 -0.0207 3.0E-01 0.0118 8.6E-01 -0.0493 2.5E-01 Alistipes_shahii UniRef90_D4IPN7 Cluster: Nucleoside-diphosphate-sugar epimerases 0.12 -0.0070 7.8E-01 8.8E-01 0.0730 1.8E-01 -0.0075 6.0E-01 0.0187 6.8E-01 -0.0012 9.7E-01 Alistipes_shahii UniRef90_I3YLN8 Cluster: DUF58 domain-containing protein 0.15 0.0091 7.8E-01 8.9E-01 -0.0116 8.8E-01 -0.0185 3.4E-01 0.0133 8.4E-01 -0.0073 8.6E-01 Alistipes_shahii UniRef90_D4IMV5 Cluster: Glycosyltransferases, probably involved in cell wall biogenesis 0.11 0.0065 7.8E-01 8.9E-01 0.0534 3.0E-01 0.0020 8.8E-01 0.0520 2.3E-01 -0.0483 9.8E-02 Alistipes_shahii UniRef90_D4IQP6 Cluster: PspC domain-containing protein 0.15 0.0093 7.8E-01 8.9E-01 0.1185 1.1E-01 0.0085 6.6E-01 0.0680 2.8E-01 0.0372 3.8E-01 Alistipes_shahii UniRef90_D4INK3 Cluster: Uridine kinase 0.19 0.0088 7.9E-01 8.9E-01 0.0302 6.8E-01 0.0040 8.3E-01 0.0983 1.1E-01 -0.0119 7.7E-01 Alistipes_shahii UniRef90_D4IN24 Cluster: His Kinase A (Phosphoacceptor) domain./Histidine kinase-, DNA 0.18 0.0081 7.9E-01 8.9E-01 0.1386 4.0E-02 -0.0197 2.8E-01 0.0881 1.2E-01 -0.0159 6.8E-01 gyrase B-, and HSP90-like ATPase Alistipes_shahii UniRef90_I3YIL2 Cluster: V-type ATP synthase alpha chain 0.24 0.0116 7.9E-01 8.9E-01 0.0267 8.0E-01 -0.0150 5.5E-01 -0.0053 9.5E-01 0.0111 8.4E-01 Alistipes_shahii UniRef90_I3YQA4 Cluster: Glutamate decarboxylase 0.12 -0.0065 7.9E-01 8.9E-01 -0.0282 6.1E-01 -0.0050 7.4E-01 0.0195 6.7E-01 -0.0525 1.1E-01 Alistipes_shahii UniRef90_D4IJC0 Cluster: AAA_31 domain-containing protein 0.11 0.0060 8.0E-01 8.9E-01 -0.0711 1.9E-01 -0.0074 5.9E-01 0.0133 7.7E-01 -0.0252 4.0E-01 Alistipes_shahii UniRef90_D4IJN6 Cluster: N-formyl-4-amino-5-aminomethyl-2-methylpyrimidin e 0.20 0.0102 8.0E-01 9.0E-01 0.0317 7.3E-01 -0.0241 3.0E-01 0.0929 2.3E-01 -0.0141 7.8E-01 Alistipes_shahii UniRef90_D4IPF6 Cluster:deformylase DNA mismatch repair protein MutL 0.20 0.0102 8.0E-01 9.0E-01 0.0813 3.8E-01 -0.0133 5.7E-01 0.1179 1.3E-01 -0.0391 4.3E-01 Alistipes_shahii UniRef90_D4IQ78 Cluster: DNA uptake protein and related DNA-binding proteins 0.15 -0.0071 8.0E-01 9.0E-01 0.0090 8.9E-01 -0.0114 4.8E-01 0.0567 2.9E-01 0.0020 9.6E-01 Alistipes_shahii UniRef90_D4IJI5 Cluster: Mannose-6-phosphate isomerase 0.14 0.0106 8.0E-01 9.0E-01 -0.0476 6.2E-01 -0.0571 2.1E-02 -0.0335 6.8E-01 -0.0385 4.7E-01 Alistipes_shahii UniRef90_D4ILK0 Cluster: GH3 auxin-responsive promoter 0.20 0.0102 8.0E-01 9.0E-01 -0.0084 9.3E-01 -0.0106 6.5E-01 -0.0098 9.0E-01 -0.0836 9.8E-02 Alistipes_shahii UniRef90_I3YHS7 Cluster: Ion-translocating oxidoreductase complex subunit A 0.12 0.0071 8.0E-01 9.0E-01 0.0437 5.0E-01 -0.0188 2.6E-01 0.0564 3.0E-01 -0.0468 1.9E-01 Alistipes_shahii UniRef90_D4IJ20 Cluster: Dihydropteroate synthase 0.11 0.0071 8.1E-01 9.0E-01 -0.0924 1.7E-01 -0.0129 4.6E-01 -0.0114 8.4E-01 -0.0304 4.2E-01

Supplementary Data 3b UniRef90 Family Plasma TMAO Red meat Red meat Choline Choline Species Cluster Name Detection member ID Rate Effect P FDR Effect P Effect P Effect P Effect P Alistipes_shahii UniRef90_D4IQ68 Cluster: ABC-type multidrug transport system, ATPase and permease 0.12 -0.0040 8.1E-01 9.0E-01 0.0145 7.0E-01 -0.0180 7.5E-02 0.0223 4.9E-01 0.0045 8.4E-01 components Alistipes_shahii UniRef90_D4IMC9 Cluster: Radical SAM protein, TIGR01212 family 0.15 0.0088 8.1E-01 9.0E-01 0.0646 4.5E-01 -0.0088 6.8E-01 0.0226 7.5E-01 -0.0281 5.4E-01 Alistipes_shahii UniRef90_D4IQF6 Cluster: N5-carboxyaminoimidazole ribonucleotide synthase 0.12 0.0068 8.2E-01 9.0E-01 0.0252 6.9E-01 -0.0158 3.4E-01 0.0002 1.0E+00 -0.0295 4.1E-01 Alistipes_shahii UniRef90_D4IM16 Cluster: Sugar phosphate permease 0.15 0.0060 8.2E-01 9.0E-01 0.0213 7.1E-01 0.0183 2.3E-01 0.0177 7.2E-01 0.0150 6.5E-01 Alistipes_shahii UniRef90_D4INS0 Cluster: SusD family 0.10 0.0043 8.2E-01 9.1E-01 0.0629 1.3E-01 0.0081 4.5E-01 0.0810 2.2E-02 0.0296 2.1E-01 Alistipes_shahii UniRef90_D4IMF7 Cluster: Fucose permease 0.22 -0.0108 8.2E-01 9.1E-01 0.0307 7.8E-01 -0.0224 4.2E-01 0.0321 7.3E-01 -0.0188 7.5E-01 Alistipes_shahii UniRef90_D4IPT9 Cluster: GTPase Obg 0.14 0.0055 8.2E-01 9.1E-01 0.0582 2.9E-01 -0.0098 5.0E-01 0.0295 5.2E-01 -0.0202 5.1E-01 Alistipes_shahii UniRef90_I3YHG3 Cluster: GTP pyrophosphokinase 0.19 -0.0064 8.3E-01 9.1E-01 0.0814 2.2E-01 -0.0129 4.4E-01 0.0449 4.2E-01 -0.0252 4.9E-01 Alistipes_shahii UniRef90_D4IPU5 Cluster: Cytosol non-specific dipeptidase 0.19 0.0087 8.3E-01 9.1E-01 0.1228 1.7E-01 -0.0068 7.7E-01 0.0469 5.3E-01 -0.0187 7.1E-01 Alistipes_shahii UniRef90_D4ILQ5 Cluster: Superfamily II DNA and RNA helicases 0.14 0.0047 8.3E-01 9.1E-01 0.0519 2.8E-01 -0.0060 6.4E-01 0.0218 5.9E-01 0.0024 9.3E-01 Alistipes_shahii UniRef90_D4IMM2 Cluster: DNA/RNA endonuclease G, NUC1 0.11 -0.0065 8.3E-01 9.1E-01 0.0748 2.7E-01 -0.0198 2.7E-01 0.1300 2.1E-02 -0.0031 9.4E-01 Alistipes_shahii UniRef90_D4ILX1 Cluster: Glycosyltransferases, probably involved in cell wall biogenesis 0.12 -0.0039 8.3E-01 9.1E-01 0.0304 4.7E-01 -0.0060 5.9E-01 0.1069 2.3E-03 -0.0028 9.1E-01 Alistipes_shahii UniRef90_D4IPS9 Cluster: Hemolysins and related proteins containing CBS domains 0.11 -0.0045 8.4E-01 9.1E-01 0.0261 5.9E-01 -0.0243 5.3E-02 0.0208 6.1E-01 -0.0493 6.9E-02 Alistipes_shahii UniRef90_D4IMS5 Cluster: Uncharacterized conserved protein 0.11 0.0071 8.4E-01 9.2E-01 0.1168 1.2E-01 0.0106 6.0E-01 0.0822 2.0E-01 -0.0341 4.3E-01 Alistipes_shahii UniRef90_D4IQ59 Cluster: Tryptophan--tRNA ligase 0.13 0.0042 8.4E-01 9.2E-01 0.0017 9.7E-01 -0.0065 6.0E-01 0.0903 2.0E-02 0.0293 2.8E-01 Alistipes_shahii UniRef90_D4IL65 Cluster: Cysteine desulfurase 0.18 0.0079 8.4E-01 9.2E-01 0.0787 3.8E-01 0.0003 9.9E-01 0.0349 6.4E-01 -0.0026 9.6E-01 Alistipes_shahii UniRef90_D4IML0 Cluster: Methionine aminopeptidase 0.21 0.0100 8.4E-01 9.2E-01 0.0611 6.0E-01 -0.0440 1.3E-01 0.1162 2.3E-01 -0.0600 3.4E-01 Alistipes_shahii UniRef90_D4IPM3 Cluster: Metallophos domain-containing protein 0.13 -0.0050 8.5E-01 9.2E-01 0.0901 1.2E-01 0.0020 8.9E-01 0.0714 1.4E-01 -0.0122 7.0E-01 Alistipes_shahii UniRef90_D4IJP9 Cluster: TonB family C-terminal domain 0.14 -0.0064 8.5E-01 9.2E-01 0.0228 7.7E-01 0.0087 6.6E-01 0.0093 8.8E-01 -0.0068 8.7E-01 Alistipes_shahii UniRef90_D4IM45 Cluster: Quinolinate synthase A 0.12 -0.0050 8.5E-01 9.2E-01 0.0767 1.9E-01 0.0025 8.8E-01 0.0677 1.8E-01 -0.0265 4.3E-01 Alistipes_shahii UniRef90_D4IJS5 Cluster: Diaminopimelate decarboxylase 0.10 0.0042 8.5E-01 9.2E-01 0.0115 8.1E-01 -0.0007 9.6E-01 0.0045 9.1E-01 -0.0415 1.4E-01 Alistipes_shahii UniRef90_D4IMW4 Cluster: N-acetyl-beta-hexosaminidase 0.15 -0.0050 8.6E-01 9.2E-01 0.0301 6.3E-01 0.0092 5.6E-01 0.0617 2.3E-01 -0.0068 8.4E-01 Alistipes_shahii UniRef90_R6VP54 Cluster: Queuine tRNA-ribosyltransferase 0.16 0.0057 8.6E-01 9.2E-01 0.0194 7.9E-01 -0.0163 3.7E-01 0.0105 8.6E-01 -0.0361 3.6E-01 Alistipes_shahii UniRef90_D4IJJ6 Cluster: Glycosyltransferases involved in cell wall biogenesis 0.11 -0.0040 8.6E-01 9.2E-01 -0.0155 7.6E-01 -0.0002 9.9E-01 0.0736 8.2E-02 -0.0141 6.2E-01 Alistipes_shahii UniRef90_D4IJ44 Cluster: Shikimate kinase 0.13 0.0063 8.6E-01 9.2E-01 -0.0044 9.6E-01 -0.0195 3.5E-01 -0.0269 6.8E-01 -0.0429 3.3E-01 Alistipes_shahii UniRef90_D4INC0 Cluster: Fe2+-dicitrate sensor, membrane component 0.16 0.0064 8.6E-01 9.2E-01 0.0787 3.3E-01 0.0183 3.9E-01 0.0883 1.9E-01 -0.0269 5.5E-01 Alistipes_shahii UniRef90_D4IJ31 Cluster: Uncharacterized ACR, YkgG family COG1556 0.11 0.0060 8.6E-01 9.3E-01 0.0923 2.3E-01 0.0276 1.7E-01 0.0550 3.9E-01 -0.0359 4.1E-01 Alistipes_shahii UniRef90_D4ILK7 Cluster: Ion-translocating oxidoreductase complex subunit C 0.18 0.0053 8.6E-01 9.3E-01 -0.0100 8.9E-01 -0.0066 7.2E-01 0.0302 6.1E-01 -0.0140 7.2E-01 Alistipes_shahii UniRef90_I3YKG4 Cluster: 30S ribosomal protein S1 0.24 -0.0075 8.7E-01 9.3E-01 0.0542 6.0E-01 -0.0256 3.2E-01 0.1279 1.4E-01 -0.0332 5.5E-01 Alistipes_shahii UniRef90_D4IMA1 Cluster: Mg-chelatase subunit ChlD 0.15 -0.0049 8.7E-01 9.3E-01 0.0933 1.7E-01 -0.0042 8.0E-01 0.0149 7.9E-01 -0.0101 7.8E-01 Alistipes_shahii UniRef90_D4IM37 Cluster: Phenylalanine--tRNA ligase alpha subunit 0.16 -0.0047 8.7E-01 9.3E-01 0.0300 6.4E-01 -0.0241 1.5E-01 0.0099 8.5E-01 -0.0110 7.6E-01 Alistipes_shahii UniRef90_D4IJ33 Cluster: Membrane-bound metallopeptidase 0.12 -0.0035 8.7E-01 9.3E-01 -0.0569 2.2E-01 -0.0039 7.5E-01 0.0036 9.3E-01 -0.0068 8.0E-01 Alistipes_shahii UniRef90_D4IL73 Cluster: Superoxide dismutase 0.18 0.0082 8.7E-01 9.3E-01 0.0498 6.7E-01 -0.0376 1.9E-01 0.0425 6.6E-01 -0.1154 6.0E-02 Alistipes_shahii UniRef90_D4IK06 Cluster: Efflux transporter, outer membrane factor (OMF) lipoprotein, NodT 0.19 0.0057 8.7E-01 9.3E-01 0.0702 3.9E-01 -0.0043 8.4E-01 0.0363 6.0E-01 0.0039 9.3E-01 family Alistipes_shahii UniRef90_D4IJ00 Cluster: Transcriptional regulator 0.16 -0.0055 8.7E-01 9.3E-01 -0.0381 6.3E-01 -0.0066 7.5E-01 0.0753 2.5E-01 -0.0089 8.4E-01 Alistipes_shahii UniRef90_R6VVR2 Cluster: ABC-type (Unclassified) transport system ATPase component 0.17 0.0059 8.8E-01 9.3E-01 0.0514 5.4E-01 -0.0130 5.5E-01 -0.0247 7.3E-01 -0.0055 9.1E-01 Alistipes_shahii UniRef90_D4IL53 Cluster: Predicted DNA-binding protein with the Helix-hairpin-helix motif 0.10 0.0034 8.8E-01 9.3E-01 0.0667 1.6E-01 -0.0038 7.7E-01 0.0696 9.0E-02 0.0115 6.8E-01 Alistipes_shahii UniRef90_D4IJT6 Cluster: Flavodoxins 0.16 0.0090 8.8E-01 9.3E-01 -0.0562 6.9E-01 0.0129 7.1E-01 0.1386 2.3E-01 -0.0304 6.8E-01 Alistipes_shahii UniRef90_D4ILG3 Cluster: Prephenate dehydrogenase 0.18 0.0061 8.8E-01 9.3E-01 0.0077 9.3E-01 -0.0056 8.1E-01 0.0480 5.4E-01 -0.0089 8.6E-01 Alistipes_shahii UniRef90_D4IQ53 Cluster: FAD synthase 0.13 -0.0032 8.8E-01 9.3E-01 0.0369 4.4E-01 0.0037 7.7E-01 0.0150 7.2E-01 -0.0120 6.7E-01 Alistipes_shahii UniRef90_D4IMD0 Cluster: Uncharacterized conserved protein 0.16 0.0040 8.9E-01 9.4E-01 0.1310 3.8E-02 0.0099 5.5E-01 0.1256 1.8E-02 0.0238 5.0E-01 Alistipes_shahii UniRef90_D4IK01 Cluster: Aldo/keto reductases, related to diketogulonate reductase 0.12 -0.0038 8.9E-01 9.3E-01 0.0354 5.4E-01 0.0073 6.4E-01 0.0299 5.4E-01 -0.0045 8.9E-01 Alistipes_shahii UniRef90_I3YQ22 Cluster: Diadenylate cyclase 0.15 0.0044 8.9E-01 9.4E-01 0.0684 3.3E-01 -0.0003 9.9E-01 0.0352 5.5E-01 -0.0566 1.6E-01 Alistipes_shahii UniRef90_D4IPZ6 Cluster: Translation factor SUA5 0.12 -0.0039 8.9E-01 9.4E-01 0.0277 6.7E-01 0.0120 4.9E-01 0.0432 4.3E-01 0.0205 5.8E-01 Alistipes_shahii UniRef90_D4IL38 Cluster: Predicted glycosyltransferases 0.12 -0.0027 9.0E-01 9.4E-01 0.0094 8.4E-01 0.0029 8.1E-01 0.0310 4.3E-01 0.0106 6.9E-01 Alistipes_shahii UniRef90_D4IJ55 Cluster: Mannitol-1-phosphate/altronate dehydrogenases 0.14 -0.0029 9.0E-01 9.4E-01 0.0264 6.0E-01 -0.0020 8.8E-01 0.0475 2.6E-01 -0.0485 8.6E-02 Alistipes_shahii UniRef90_D4IM47 Cluster: Signal peptide peptidase SppA, 67K type 0.17 -0.0031 9.0E-01 9.4E-01 0.0823 1.5E-01 -0.0239 9.9E-02 -0.0015 9.8E-01 -0.0214 4.9E-01 Alistipes_shahii UniRef90_D4INB6 Cluster: Predicted dehydrogenases and related proteins 0.20 -0.0057 9.0E-01 9.4E-01 0.1099 3.0E-01 -0.0054 8.4E-01 0.0785 3.7E-01 -0.0595 2.9E-01 Alistipes_shahii UniRef90_D4IPA2 Cluster: GP-PDE domain-containing protein 0.20 0.0052 9.1E-01 9.4E-01 -0.0152 8.8E-01 -0.0012 9.6E-01 0.0262 7.6E-01 -0.0391 4.7E-01 Alistipes_shahii UniRef90_D4INI7 Cluster: Tyrosine--tRNA ligase 0.19 0.0037 9.1E-01 9.5E-01 0.0040 9.6E-01 -0.0019 9.2E-01 0.0993 9.9E-02 0.0127 7.5E-01 Alistipes_shahii UniRef90_D4IJP4 Cluster: Thioredoxin 0.16 -0.0028 9.1E-01 9.5E-01 0.0208 7.1E-01 0.0030 8.4E-01 0.0721 1.3E-01 0.0235 4.6E-01 Alistipes_shahii UniRef90_D4IME9 Cluster: Glycogen synthase 1 0.20 -0.0055 9.1E-01 9.5E-01 0.0459 6.9E-01 -0.0100 7.2E-01 0.0122 9.0E-01 0.0166 7.8E-01 Alistipes_shahii UniRef90_D4IJG5 Cluster: TonB_dep_Rec domain-containing protein 0.19 -0.0038 9.1E-01 9.5E-01 0.0104 9.0E-01 -0.0309 1.3E-01 0.0132 8.4E-01 -0.0934 3.4E-02 Alistipes_shahii UniRef90_D4INJ2 Cluster: Acylneuraminate cytidylyltransferase family protein 0.11 -0.0023 9.1E-01 9.5E-01 0.0692 1.3E-01 0.0085 5.0E-01 0.0502 2.0E-01 0.0286 2.9E-01 Alistipes_shahii UniRef90_I3YNU0 Cluster: Ribonuclease, Rne/Rng family 0.18 0.0027 9.2E-01 9.5E-01 0.0219 7.0E-01 0.0042 7.7E-01 0.0409 3.9E-01 0.0125 6.9E-01 Alistipes_shahii UniRef90_D4IP85 Cluster: Periplasmic serine protease, Do/DeqQ family 0.18 0.0035 9.2E-01 9.5E-01 0.0277 7.1E-01 -0.0037 8.5E-01 0.0854 1.7E-01 -0.0303 4.6E-01 Alistipes_shahii UniRef90_D4INH3 Cluster: Fructose-bisphosphate aldolase 0.20 0.0039 9.2E-01 9.5E-01 0.0318 7.2E-01 -0.0292 1.8E-01 0.1200 1.0E-01 -0.0315 5.0E-01 Alistipes_shahii UniRef90_D4IMK2 Cluster: 50S ribosomal protein L24 0.15 0.0042 9.2E-01 9.5E-01 0.0396 6.8E-01 -0.0231 3.6E-01 0.1248 1.3E-01 -0.0408 4.6E-01 Alistipes_shahii UniRef90_I3YLW4 Cluster: S-adenosylmethionine:tRNA ribosyltransferase-isomerase 0.18 -0.0031 9.2E-01 9.5E-01 0.0703 3.3E-01 -0.0313 8.6E-02 0.0657 2.7E-01 -0.0868 2.8E-02 Alistipes_shahii UniRef90_D4IQ62 Cluster: KpsF/GutQ family protein 0.16 0.0032 9.3E-01 9.6E-01 -0.0052 9.5E-01 -0.0052 8.0E-01 0.0477 4.6E-01 0.0451 2.9E-01 Alistipes_shahii UniRef90_D4IPU0 Cluster: 3-isopropylmalate dehydrogenase 0.11 -0.0026 9.3E-01 9.6E-01 0.0459 4.5E-01 -0.0097 5.5E-01 0.0719 1.5E-01 0.0527 1.4E-01 Alistipes_shahii UniRef90_D4IJY1 Cluster: Predicted oxidoreductase related to nitroreductase 0.15 0.0042 9.3E-01 9.6E-01 -0.0581 5.7E-01 0.0000 1.0E+00 0.0488 5.7E-01 -0.0187 7.4E-01 Alistipes_shahii UniRef90_D4IL29 Cluster: Outer membrane cobalamin receptor protein 0.14 0.0025 9.3E-01 9.5E-01 0.0268 6.6E-01 -0.0140 3.8E-01 -0.0278 5.9E-01 0.0731 3.2E-02 Alistipes_shahii UniRef90_D4IJL3 Cluster: Formate-dependent phosphoribosylglycinamide formyltransferase 0.11 0.0019 9.3E-01 9.6E-01 -0.0243 6.2E-01 -0.0087 5.0E-01 0.0057 8.9E-01 -0.0138 6.2E-01 Alistipes_shahii UniRef90_D4IMA0 Cluster: Mg-chelatase subunit ChlD 0.13 -0.0022 9.3E-01 9.6E-01 0.0534 3.6E-01 -0.0003 9.8E-01 0.1074 2.8E-02 -0.0438 1.8E-01 Alistipes_shahii UniRef90_D4INJ6 Cluster: rRNA methylases 0.13 -0.0022 9.4E-01 9.6E-01 0.0676 2.8E-01 0.0080 6.3E-01 0.0880 1.0E-01 -0.0234 5.1E-01 Alistipes_shahii UniRef90_D4IK00 Cluster: 4Fe-4S binding domain 0.13 0.0019 9.5E-01 9.7E-01 -0.0014 9.8E-01 -0.0206 2.0E-01 0.0661 2.0E-01 -0.0252 4.7E-01 Alistipes_shahii UniRef90_D4IPG7 Cluster: SusD family 0.21 0.0039 9.5E-01 9.7E-01 0.0437 7.6E-01 -0.0379 2.7E-01 0.1171 3.1E-01 -0.1662 2.4E-02 Alistipes_shahii UniRef90_D4INB5 Cluster: Sec-independent protein translocase protein TatC 0.17 -0.0020 9.5E-01 9.7E-01 0.0747 3.0E-01 -0.0015 9.3E-01 0.0123 8.4E-01 0.0166 6.7E-01 Alistipes_shahii UniRef90_D4IL52 Cluster: RNA-binding proteins (RRM domain) 0.13 0.0035 9.5E-01 9.7E-01 0.1085 3.7E-01 0.0224 4.7E-01 0.0103 9.2E-01 -0.0043 9.5E-01 Alistipes_shahii UniRef90_D4IPA1 Cluster: Alpha-galactosidase 0.16 0.0016 9.5E-01 9.7E-01 0.0034 9.6E-01 -0.0149 3.4E-01 0.0492 3.5E-01 -0.0584 8.3E-02 Alistipes_shahii UniRef90_D4IPF8 Cluster: Metal-dependent hydrolase 0.15 -0.0016 9.6E-01 9.8E-01 0.0975 1.3E-01 0.0212 2.1E-01 -0.0396 4.7E-01 -0.0158 6.6E-01 Alistipes_shahii UniRef90_D4IQG4 Cluster: Dihydroorotate dehydrogenase B (NAD(+)), electron transfer 0.10 0.0013 9.6E-01 9.8E-01 0.0013 9.8E-01 -0.0052 7.1E-01 0.0586 1.8E-01 -0.0101 7.3E-01 Alistipes_shahii UniRef90_D4INQ1 Cluster:subunit Permeases of the drug/metabolite transporter (DMT) superfamily 0.12 -0.0012 9.6E-01 9.8E-01 0.0550 3.5E-01 -0.0023 8.8E-01 0.0549 2.7E-01 0.0440 1.9E-01 Alistipes_shahii UniRef90_D4IQN3 Cluster: UvrABC system protein C 0.16 -0.0010 9.6E-01 9.8E-01 0.0277 5.8E-01 -0.0059 6.5E-01 0.1078 8.5E-03 -0.0363 1.9E-01 Alistipes_shahii UniRef90_I3YHS8 Cluster: Ion-translocating oxidoreductase complex subunit E 0.15 -0.0016 9.6E-01 9.8E-01 -0.1071 2.0E-01 0.0076 7.2E-01 0.0050 9.4E-01 -0.0019 9.7E-01 Alistipes_shahii UniRef90_D4IQD1 Cluster: Glutamine-dependent NAD(+) synthetase 0.14 -0.0008 9.7E-01 9.8E-01 0.0316 4.6E-01 -0.0049 6.6E-01 0.0578 1.1E-01 0.0066 7.8E-01 Alistipes_shahii UniRef90_D4IQF3 Cluster: Phosphoribosylaminoimidazole-succinocarboxamide synthase 0.15 -0.0009 9.7E-01 9.8E-01 0.0600 3.3E-01 -0.0171 2.9E-01 0.0143 7.8E-01 0.0106 7.6E-01 Alistipes_shahii UniRef90_D4ILW6 Cluster: Uracil phosphoribosyltransferase 0.14 -0.0010 9.7E-01 9.8E-01 0.0243 7.2E-01 -0.0311 7.8E-02 0.0783 1.7E-01 -0.0062 8.7E-01 Alistipes_shahii UniRef90_D4IP39 Cluster: Transcriptional regulators 0.11 0.0010 9.8E-01 9.8E-01 0.1338 6.2E-02 -0.0080 6.7E-01 0.0161 7.9E-01 -0.0126 7.6E-01 Alistipes_shahii UniRef90_D4IMW0 Cluster: Tyrosine recombinase XerC 0.18 -0.0010 9.8E-01 9.9E-01 0.0201 8.4E-01 0.0242 3.4E-01 0.0867 2.9E-01 0.0314 5.6E-01 Alistipes_shahii UniRef90_D4IPQ6 Cluster: Predicted Zn-dependent peptidases 0.10 -0.0003 9.8E-01 9.9E-01 0.0360 3.1E-01 -0.0161 8.7E-02 0.0221 4.6E-01 0.0059 7.7E-01 Alistipes_shahii UniRef90_D4IIN6 Cluster: Subtilisin-like serine proteases 0.16 -0.0005 9.9E-01 9.9E-01 0.0315 6.1E-01 -0.0046 7.7E-01 0.0624 2.3E-01 -0.0298 3.9E-01 Alistipes_shahii UniRef90_D4IP93 Cluster: tRNA (guanine-N(7)-)-methyltransferase 0.11 -0.0004 9.9E-01 9.9E-01 -0.0818 1.7E-01 -0.0185 2.6E-01 -0.0335 5.1E-01 -0.0164 6.4E-01 Alistipes_shahii UniRef90_I3YQ86 Cluster: NADH peroxidase 0.21 0.0006 9.9E-01 9.9E-01 0.0218 8.8E-01 -0.0387 2.8E-01 -0.0199 8.7E-01 -0.0569 4.6E-01 Alistipes_shahii UniRef90_D4IKW3 Cluster: Fe-S oxidoreductases 0.11 -0.0001 1.0E+00 1.0E+00 0.0110 8.3E-01 0.0105 4.3E-01 -0.0414 3.4E-01 0.0368 2.0E-01 Alistipes_shahii UniRef90_D4ILV9 Cluster: C-terminal peptidase (Prc) 0.14 0.0000 1.0E+00 1.0E+00 0.0453 3.0E-01 -0.0147 2.0E-01 0.0459 2.1E-01 -0.0225 3.6E-01 Eubacterium_hallii UniRef90_R5GP06 Cluster: CTP synthase 0.10 0.0559 1.9E-02 2.7E-01 0.0030 9.5E-01 -0.0184 1.9E-01 0.0546 2.2E-01 0.0177 5.5E-01 Eubacterium_hallii UniRef90_R6G9Y3 Cluster: Inosine-5'-monophosphate dehydrogenase 0.11 0.0551 2.5E-02 2.9E-01 0.0306 5.7E-01 -0.0101 4.9E-01 0.0411 3.8E-01 0.0343 2.8E-01 Eubacterium_hallii UniRef90_R5GCG3 Cluster: Protein GrpE 0.10 0.0811 3.1E-02 2.7E-01 -0.0460 5.8E-01 -0.0133 5.5E-01 0.0356 6.1E-01 0.0504 3.0E-01 Eubacterium_hallii UniRef90_R5GA27 Cluster: DUF1667 domain-containing protein 0.16 0.1210 3.1E-02 2.7E-01 0.0110 9.3E-01 -0.0133 6.8E-01 0.0275 8.0E-01 -0.0501 4.7E-01 Eubacterium_hallii UniRef90_R6G856 Cluster: Aldehyde dehydrogenase EutE 0.25 0.1060 5.0E-02 3.2E-01 -0.1583 1.9E-01 -0.0066 8.3E-01 -0.0006 1.0E+00 0.0213 7.5E-01 53

Supplementary Data 3b UniRef90 Family Plasma TMAO Red meat Red meat Choline Choline Species Cluster Name Detection member ID Rate Effect P FDR Effect P Effect P Effect P Effect P Eubacterium_hallii UniRef90_R6FVU8 Cluster: 4-hydroxy-tetrahydrodipicolinate reductase 0.11 0.0585 5.7E-02 3.3E-01 -0.0883 2.2E-01 -0.0044 8.2E-01 -0.0026 9.7E-01 0.0389 3.4E-01 Eubacterium_hallii UniRef90_R5GLY5 Cluster: Phosphoglycerate kinase 0.18 0.0640 6.4E-02 3.4E-01 -0.0525 4.9E-01 -0.0246 2.4E-01 -0.0485 4.6E-01 0.0235 6.0E-01 Eubacterium_hallii UniRef90_R5GN58 Cluster: Ribosome hibernation promoting factor 0.19 0.1237 6.7E-02 3.4E-01 -0.2466 1.0E-01 -0.0206 6.0E-01 0.0661 6.0E-01 0.1389 1.0E-01 Eubacterium_hallii UniRef90_R6GA24 Cluster: RNA polymerase sigma factor SigA 0.11 0.0507 8.5E-02 3.7E-01 -0.0293 6.5E-01 -0.0121 4.8E-01 0.0087 8.7E-01 0.0212 5.7E-01 Eubacterium_hallii UniRef90_R5GK97 Cluster: Predicted metal-binding protein related to the C-terminal domain 0.11 0.0652 8.5E-02 3.7E-01 -0.1301 1.3E-01 -0.0319 1.5E-01 -0.0115 8.7E-01 0.0168 7.3E-01 of SecA Eubacterium_hallii UniRef90_C4Z763 Cluster: GTP pyrophosphokinase ywaC 0.14 0.0141 8.5E-02 3.7E-01 -0.0036 8.4E-01 -0.0051 2.9E-01 0.0053 7.2E-01 -0.0105 3.1E-01 Eubacterium_hallii UniRef90_D4MXT9 Cluster: Phage_integrase domain-containing protein 0.19 0.0168 8.6E-02 3.7E-01 -0.0188 4.0E-01 -0.0023 7.0E-01 0.0048 8.0E-01 0.0125 3.2E-01 Eubacterium_hallii UniRef90_R5GJH6 Cluster: Dehydratase medium subunit 0.14 0.0830 8.7E-02 3.7E-01 -0.2193 3.8E-02 -0.0245 3.9E-01 -0.0439 6.2E-01 -0.0181 7.7E-01 Eubacterium_hallii UniRef90_R6FXA2 Cluster: Mannitol-1-phosphate 5-dehydrogenase 0.10 0.0363 1.1E-01 4.0E-01 0.0415 4.1E-01 0.0160 2.4E-01 0.0000 1.0E+00 0.0491 9.4E-02 Eubacterium_hallii UniRef90_R6GT82 Cluster: 4-hydroxy-tetrahydrodipicolinate synthase 0.11 -0.0457 1.1E-01 4.0E-01 -0.0744 2.4E-01 -0.0149 3.8E-01 0.0378 4.9E-01 0.0391 2.9E-01 Eubacterium_hallii UniRef90_R6G6Z6 Cluster: NADH-quinone oxidoreductase subunit 1 0.11 0.0395 1.1E-01 4.0E-01 -0.1030 6.5E-02 -0.0080 5.9E-01 -0.0529 2.6E-01 0.0413 2.0E-01 Eubacterium_hallii UniRef90_R5G775 Cluster: [formate-C-acetyltransferase]-activating enzyme 0.24 0.1036 1.3E-01 4.2E-01 -0.3691 1.5E-02 -0.0420 3.0E-01 -0.0754 5.5E-01 0.0353 6.9E-01 Eubacterium_hallii UniRef90_R6NDP6 Cluster: 50S ribosomal protein L27 0.12 0.0649 1.3E-01 4.2E-01 -0.0450 6.4E-01 -0.0178 4.8E-01 -0.0095 9.0E-01 0.0326 5.5E-01 Eubacterium_hallii UniRef90_R6GXJ8 Cluster: Ribose-phosphate diphosphokinase 0.15 0.0511 1.4E-01 4.3E-01 -0.0400 6.0E-01 -0.0010 9.6E-01 0.1144 7.1E-02 0.0300 5.0E-01 Eubacterium_hallii UniRef90_R6FXF5 Cluster: Periplasmic serine endoprotease DegP 0.15 0.0414 1.5E-01 4.4E-01 -0.0353 5.9E-01 -0.0150 3.7E-01 -0.0115 8.3E-01 0.0491 1.7E-01 Eubacterium_hallii UniRef90_N2A4M1 Cluster: CO dehydrogenase flavoprotein-like, FAD-binding, subdomain 2 0.21 0.0748 1.6E-01 4.5E-01 -0.1723 1.7E-01 -0.0309 3.3E-01 -0.0121 9.1E-01 0.0388 5.7E-01 Eubacterium_hallii UniRef90_R6FZ86 Cluster: DegV: EDD domain protein, DegV family 0.10 0.0404 1.7E-01 4.5E-01 -0.0119 8.6E-01 -0.0156 3.7E-01 0.0120 8.3E-01 0.0074 8.4E-01 Eubacterium_hallii UniRef90_R6GXK4 Cluster: Hydrogenase, Fe-only 0.14 0.0363 1.7E-01 4.5E-01 -0.0564 3.4E-01 -0.0016 9.2E-01 0.0007 9.9E-01 0.0222 5.1E-01 Eubacterium_hallii UniRef90_R6GAN5 Cluster: Ribonuclease Y 0.17 0.0501 1.7E-01 4.5E-01 -0.0975 2.3E-01 -0.0340 1.1E-01 -0.0363 6.0E-01 -0.0024 9.6E-01 Eubacterium_hallii UniRef90_R5GQ94 Cluster: Hsp20/alpha crystallin family protein 0.15 0.0810 1.8E-01 4.5E-01 0.0175 9.0E-01 -0.0248 4.7E-01 0.0996 3.8E-01 0.1275 8.4E-02 Eubacterium_hallii UniRef90_R6GB00 Cluster: S-adenosylmethionine synthase 0.24 0.0957 1.8E-01 4.6E-01 -0.4298 6.4E-03 -0.0411 3.4E-01 -0.0067 9.6E-01 0.0206 8.2E-01 Eubacterium_hallii UniRef90_R6GUE4 Cluster: Flavoprotein domain-containing protein 0.22 0.0674 1.9E-01 4.6E-01 -0.1556 1.7E-01 -0.0398 1.8E-01 -0.0061 9.5E-01 0.0140 8.3E-01 Eubacterium_hallii UniRef90_U2RFY0 Cluster: GMP synthase [glutamine-hydrolyzing] 0.13 0.0332 2.1E-01 4.9E-01 -0.1034 8.4E-02 -0.0109 4.9E-01 -0.0055 9.1E-01 0.0453 1.8E-01 Eubacterium_hallii UniRef90_R5GKK0 Cluster: L-lactate permease 0.16 0.0573 2.2E-01 5.0E-01 -0.1453 1.7E-01 -0.0255 3.6E-01 0.0381 6.7E-01 0.1143 5.3E-02 Eubacterium_hallii UniRef90_R5GB32 Cluster: Acetyl-CoA C-acetyltransferase 0.27 0.0823 2.4E-01 5.1E-01 -0.3100 4.8E-02 -0.0768 6.4E-02 -0.0223 8.7E-01 0.0547 5.4E-01 Eubacterium_hallii UniRef90_R6G8G4 Cluster: Glutamine--fructose-6-phosphate aminotransferase [isomerizing] 0.19 0.0434 2.4E-01 5.1E-01 -0.0467 5.7E-01 -0.0213 3.3E-01 0.0628 3.7E-01 0.0702 1.4E-01 Eubacterium_hallii UniRef90_R5GDR5 Cluster: Cell division protein FtsZ 0.11 0.0306 2.5E-01 5.2E-01 -0.0951 1.0E-01 -0.0207 1.9E-01 0.0064 8.9E-01 0.0413 2.2E-01 Eubacterium_hallii UniRef90_R5GEP3 Cluster: ATP synthase subunit beta 0.14 0.0246 2.6E-01 5.3E-01 -0.0019 9.7E-01 -0.0070 5.9E-01 -0.0248 5.4E-01 -0.0044 8.8E-01 Eubacterium_hallii UniRef90_R6GSV5 Cluster: Twitching motility protein PilT 0.16 0.0604 2.6E-01 5.3E-01 -0.1990 9.4E-02 -0.0365 2.6E-01 -0.0636 5.3E-01 0.0327 6.3E-01 Eubacterium_hallii UniRef90_D4LY41 Cluster: Signal transduction histidine-protein kinase BaeS 0.14 -0.0036 2.7E-01 5.4E-01 -0.0022 7.6E-01 0.0003 8.6E-01 0.0035 5.7E-01 -0.0031 4.6E-01 Eubacterium_hallii UniRef90_R6G1I7 Cluster: Cytidylate kinase 0.22 -0.0750 3.0E-01 5.6E-01 -0.1322 4.2E-01 -0.0524 2.2E-01 0.0773 5.8E-01 0.0479 6.0E-01 Eubacterium_hallii UniRef90_R6G8S2 Cluster: Glycine--tRNA ligase 0.11 0.0243 3.0E-01 5.6E-01 -0.0063 9.0E-01 0.0049 7.2E-01 0.0029 9.5E-01 0.0225 4.5E-01 Eubacterium_hallii UniRef90_R6GVP6 Cluster: Glycerol dehydrogenase 0.12 -0.0391 3.2E-01 5.8E-01 -0.1586 7.7E-02 0.0016 9.5E-01 -0.0348 6.5E-01 0.0528 3.0E-01 Eubacterium_hallii UniRef90_R6G9K3 Cluster: 50S ribosomal protein L5 0.14 -0.0385 3.3E-01 5.8E-01 0.0498 5.6E-01 -0.0082 7.3E-01 -0.0303 6.8E-01 0.0648 2.0E-01 Eubacterium_hallii UniRef90_R5G6N7 Cluster: BMC domain-containing protein 0.21 0.0600 3.3E-01 5.9E-01 -0.1857 1.9E-01 -0.0545 1.4E-01 0.1097 3.5E-01 0.0705 3.7E-01 Eubacterium_hallii UniRef90_R5GM56 Cluster: 50S ribosomal protein L4 0.13 0.0350 3.4E-01 6.0E-01 0.0474 5.7E-01 -0.0053 8.0E-01 -0.0432 5.3E-01 0.0335 4.7E-01 Eubacterium_hallii UniRef90_R6FWX7 Cluster: Electron transport complex protein RnfC 0.24 0.0468 3.5E-01 6.0E-01 -0.1152 2.9E-01 -0.0414 1.6E-01 -0.0221 8.1E-01 -0.0223 7.2E-01 Eubacterium_hallii UniRef90_R6G1M6 Cluster: Galactoside ABC transporter permease 0.17 -0.0237 3.5E-01 6.0E-01 -0.0479 3.8E-01 -0.0125 4.0E-01 0.0050 9.1E-01 0.0009 9.8E-01 Eubacterium_hallii UniRef90_R6GSU8 Cluster: HPr family phosphocarrier protein 0.12 0.0507 3.6E-01 6.1E-01 -0.0931 4.4E-01 -0.0098 7.6E-01 0.0714 4.9E-01 -0.0111 8.7E-01 Eubacterium_hallii UniRef90_D4L240 Cluster: CDP-diacylglycerol--glycerol-3-phosphate 3-phosphatidyltransferase 0.15 -0.0056 3.6E-01 6.1E-01 -0.0031 8.2E-01 -0.0009 8.1E-01 0.0234 3.5E-02 -0.0018 8.2E-01 Eubacterium_hallii UniRef90_R6FVE0 Cluster: Acyl-CoA dehydrogenase 0.23 0.0612 3.7E-01 6.1E-01 -0.2847 6.2E-02 -0.0382 3.5E-01 -0.0316 8.1E-01 0.0795 3.6E-01 Eubacterium_hallii UniRef90_C4ZFD9 Cluster: DNA-binding response regulator 0.16 -0.0063 3.7E-01 6.1E-01 -0.0103 5.0E-01 -0.0008 8.5E-01 0.0195 1.4E-01 -0.0058 5.2E-01 Eubacterium_hallii UniRef90_R6FWY1 Cluster: Cell division protein FtsA 0.19 0.0387 3.8E-01 6.2E-01 -0.2276 1.8E-02 -0.0260 3.2E-01 -0.0576 4.8E-01 0.0051 9.3E-01 Eubacterium_hallii UniRef90_R6G0F6 Cluster: Acyl-CoA dehydrogenase, C-terminal domain protein 0.24 0.0439 3.8E-01 6.2E-01 -0.0788 4.9E-01 -0.0202 5.0E-01 0.0384 6.9E-01 0.0046 9.4E-01 Eubacterium_hallii UniRef90_R6GTN2 Cluster: PTS-dependent dihydroxyacetone kinase, dihydroxyacetone-binding 0.12 0.0238 3.8E-01 6.2E-01 -0.0755 2.2E-01 -0.0090 5.8E-01 0.0177 7.3E-01 0.0311 3.8E-01 subunit DhaK Eubacterium_hallii UniRef90_R6GA70 Cluster: Aquaporin family protein 0.25 0.0643 3.9E-01 6.3E-01 -0.2662 1.2E-01 -0.0734 9.7E-02 -0.0177 9.0E-01 0.1053 2.7E-01 Eubacterium_hallii UniRef90_R6GCZ0 Cluster: 60 kDa chaperonin 0.19 -0.0263 4.0E-01 6.4E-01 0.0084 9.1E-01 -0.0001 1.0E+00 0.0382 5.3E-01 0.0604 1.4E-01 Eubacterium_hallii UniRef90_R5GD12 Cluster: Glucose-6-phosphate isomerase 0.15 -0.0294 4.1E-01 6.5E-01 0.0130 8.7E-01 -0.0095 6.6E-01 -0.0018 9.8E-01 0.0669 1.4E-01 Eubacterium_hallii UniRef90_C4ZHG9 Cluster: Rhodanese domain-containing protein 0.11 -0.0039 4.1E-01 6.5E-01 -0.0075 4.7E-01 0.0006 8.3E-01 -0.0051 5.6E-01 -0.0026 6.6E-01 Eubacterium_hallii UniRef90_R6G778 Cluster: Propionyl-CoA:succinate CoA transferase 0.15 0.0311 4.1E-01 6.5E-01 -0.1358 1.1E-01 -0.0236 2.9E-01 -0.0091 9.0E-01 0.0044 9.3E-01 Eubacterium_hallii UniRef90_R5GN52 Cluster: 30S ribosomal protein S2 0.19 0.0278 4.2E-01 6.5E-01 -0.0040 9.6E-01 -0.0102 6.0E-01 -0.0073 9.1E-01 0.0304 4.7E-01 Eubacterium_hallii UniRef90_R6FVJ5 Cluster: Cytidylate kinase 0.10 0.0267 4.2E-01 6.5E-01 -0.0147 8.4E-01 0.0049 8.0E-01 0.0019 9.8E-01 0.0356 3.9E-01 Eubacterium_hallii UniRef90_R6GVX1 Cluster: D-galactose/ D-glucose-binding protein 0.21 0.0388 4.2E-01 6.5E-01 -0.1625 1.2E-01 -0.0764 6.7E-03 -0.0428 6.3E-01 0.0138 8.2E-01 Eubacterium_hallii UniRef90_R6G786 Cluster: Phosphoenolpyruvate-protein phosphotransferase 0.27 0.0470 4.2E-01 6.5E-01 -0.2064 1.1E-01 -0.0280 4.1E-01 0.0919 4.0E-01 0.0653 3.7E-01 Eubacterium_hallii UniRef90_R5G9M7 Cluster: NADH peroxidase 0.14 0.0359 4.3E-01 6.5E-01 0.0076 9.4E-01 -0.0200 4.4E-01 -0.0280 7.4E-01 0.0823 1.4E-01 Eubacterium_hallii UniRef90_D4JN77 Cluster: HTH cro/C1-type domain-containing protein 0.20 0.0107 4.4E-01 6.6E-01 -0.0282 3.8E-01 -0.0109 1.9E-01 0.0320 2.4E-01 -0.0186 3.0E-01 Eubacterium_hallii UniRef90_R5G6L8 Cluster: Alcohol dehydrogenase, iron-dependent 0.18 0.0310 4.5E-01 6.7E-01 -0.0700 4.4E-01 -0.0188 4.4E-01 -0.0251 7.4E-01 0.0498 3.4E-01 Eubacterium_hallii UniRef90_R5G816 Cluster: Glycerol kinase 0.30 0.0503 4.6E-01 6.8E-01 -0.2987 5.1E-02 -0.1085 6.8E-03 -0.0469 7.2E-01 0.0926 2.8E-01 Eubacterium_hallii UniRef90_R6G0B4 Cluster: Corrinoid adenosyltransferase 0.24 0.0415 4.7E-01 6.8E-01 -0.1654 1.9E-01 -0.0383 2.6E-01 0.1088 3.1E-01 0.0052 9.4E-01 Eubacterium_hallii UniRef90_R6G8Y1 Cluster: Diol dehydratase reactivase subunit alpha 0.27 0.0436 4.7E-01 6.8E-01 -0.2066 1.3E-01 -0.0224 5.3E-01 0.0417 7.1E-01 0.0472 5.4E-01 Eubacterium_hallii UniRef90_R6GDL6 Cluster: Hsp20/alpha crystallin family protein 0.14 -0.0442 4.8E-01 6.9E-01 0.1608 2.5E-01 -0.0012 9.7E-01 0.0997 4.0E-01 0.0082 9.2E-01 Eubacterium_hallii UniRef90_R5GD40 Cluster: BMC domain 0.13 0.0307 4.9E-01 7.1E-01 -0.1268 2.0E-01 -0.0533 4.5E-02 0.0179 8.3E-01 0.0716 2.1E-01 Eubacterium_hallii UniRef90_R6G915 Cluster: 3-hydroxyacyl-CoA dehydrogenase signature 0.26 0.0452 5.1E-01 7.3E-01 -0.2990 5.6E-02 -0.0365 3.8E-01 -0.0158 9.1E-01 0.0114 9.0E-01 Eubacterium_hallii UniRef90_R6GX84 Cluster: Ribosome-recycling factor 0.11 0.0234 5.2E-01 7.3E-01 -0.0988 2.3E-01 -0.0216 3.3E-01 -0.1304 6.0E-02 -0.0356 4.5E-01 Eubacterium_hallii UniRef90_C4ZBX9 Cluster: ABC transporter 0.13 -0.0173 5.2E-01 7.3E-01 -0.0831 1.5E-01 -0.0193 2.2E-01 -0.0527 2.9E-01 -0.0411 2.3E-01 Eubacterium_hallii UniRef90_C4Z2D9 Cluster: Two-component system histidine kinase 0.11 0.0030 5.3E-01 7.4E-01 0.0020 8.5E-01 -0.0021 4.6E-01 -0.0022 8.1E-01 0.0025 6.9E-01 Eubacterium_hallii UniRef90_R6G975 Cluster: Bacterial Ig-like domain (Group 2) 0.15 0.0318 5.4E-01 7.5E-01 -0.0650 5.7E-01 -0.0099 7.5E-01 0.1028 2.7E-01 -0.0358 5.9E-01 Eubacterium_hallii UniRef90_R6G0R1 Cluster: 50S ribosomal protein L7/L12 0.11 0.0288 5.5E-01 7.6E-01 0.1021 3.4E-01 0.0329 2.4E-01 -0.0036 9.7E-01 0.0733 2.3E-01 Eubacterium_hallii UniRef90_D4MZR3 Cluster: OrfB_Zn_ribbon domain-containing protein 0.14 0.0078 5.5E-01 7.6E-01 -0.0177 5.5E-01 -0.0109 1.7E-01 0.0107 6.5E-01 0.0104 5.4E-01 Eubacterium_hallii UniRef90_R5GAG1 Cluster: FtsH protease regulator HflK 0.14 0.0157 5.6E-01 7.7E-01 -0.0087 8.8E-01 -0.0011 9.5E-01 -0.0248 6.2E-01 0.0148 6.7E-01 Eubacterium_hallii UniRef90_R6GBX8 Cluster: Putative septation protein SpoVG 0.12 0.0248 5.6E-01 7.7E-01 -0.1933 3.9E-02 -0.0177 4.8E-01 -0.1109 1.6E-01 -0.0148 7.9E-01 Eubacterium_hallii UniRef90_R6GB27 Cluster: 50S ribosomal protein L1 0.12 0.0176 5.7E-01 7.7E-01 -0.0949 1.8E-01 0.0026 8.9E-01 -0.0389 5.1E-01 0.0275 4.9E-01 Eubacterium_hallii UniRef90_R5GB72 Cluster: 4-hydroxyphenylacetate decarboxylase large subunit 0.26 0.0376 5.7E-01 7.7E-01 -0.3036 4.0E-02 -0.0453 2.5E-01 -0.0100 9.4E-01 0.0012 9.9E-01 Eubacterium_hallii UniRef90_R6GAG5 Cluster: DNA-directed RNA polymerase subunit P 0.12 -0.0154 5.8E-01 7.8E-01 -0.0601 3.3E-01 -0.0088 6.0E-01 0.0144 7.8E-01 0.0166 6.4E-01 Eubacterium_hallii UniRef90_R6FYK6 Cluster: Electron transfer flavoprotein beta subunit/FixA family protein 0.20 0.0289 5.8E-01 7.8E-01 -0.2850 1.5E-02 -0.0802 1.2E-02 -0.0262 7.9E-01 0.0426 5.4E-01 Eubacterium_hallii UniRef90_R5GKK2 Cluster: Lar_N domain-containing protein 0.23 0.0389 5.8E-01 7.8E-01 -0.1737 2.7E-01 -0.0356 4.0E-01 -0.0636 6.3E-01 0.1104 2.2E-01 Eubacterium_hallii UniRef90_R6FX92 Cluster: BIG2 domain-containing protein 0.19 -0.0391 5.9E-01 7.8E-01 -0.1168 4.7E-01 -0.0049 9.1E-01 0.0831 5.5E-01 -0.0141 8.8E-01 Eubacterium_hallii UniRef90_C0ETH6 Cluster: Transposase (Fragment) 0.12 -0.0081 5.9E-01 7.8E-01 -0.0478 1.5E-01 -0.0077 3.9E-01 0.0133 6.4E-01 -0.0059 7.6E-01 Eubacterium_hallii UniRef90_R6GUJ6 Cluster: Enoyl-CoA hydratase 0.27 0.0383 5.9E-01 7.9E-01 -0.1714 2.7E-01 -0.0542 2.0E-01 0.1281 3.4E-01 -0.0131 8.9E-01 Eubacterium_hallii UniRef90_R6FZT9 Cluster: Glucose-1-phosphate adenylyltransferase 0.14 0.0164 6.0E-01 7.9E-01 -0.0468 5.0E-01 -0.0190 2.9E-01 0.0017 9.8E-01 0.0588 1.3E-01 Eubacterium_hallii UniRef90_D4K7L5 Cluster: Cardiolipin synthase 0.18 -0.0048 6.0E-01 7.9E-01 -0.0068 7.5E-01 -0.0001 9.9E-01 0.0379 2.8E-02 -0.0117 3.1E-01 Eubacterium_hallii UniRef90_R5GK93 Cluster: Propanediol utilization microcompartment protein PduA 0.20 0.0375 6.0E-01 7.9E-01 -0.3331 4.1E-02 -0.0379 3.8E-01 -0.0021 9.9E-01 0.1253 1.7E-01 Eubacterium_hallii UniRef90_R5GMD3 Cluster: Class II fructose-1,6-bisphosphate aldolase 0.14 -0.0158 6.1E-01 7.9E-01 -0.0433 5.3E-01 -0.0108 5.6E-01 0.0266 6.5E-01 0.0065 8.7E-01 Eubacterium_hallii UniRef90_R6G0C1 Cluster: Propanediol utilization protein PduB 0.24 0.0316 6.1E-01 7.9E-01 -0.3263 1.8E-02 -0.0329 3.8E-01 -0.0409 7.3E-01 0.0451 5.7E-01 Eubacterium_hallii UniRef90_R6G6M7 Cluster: Electron transfer flavoprotein subunit alpha/FixB family protein 0.22 0.0314 6.1E-01 7.9E-01 -0.1674 2.3E-01 -0.0823 2.7E-02 0.1250 2.9E-01 0.0423 5.9E-01 Eubacterium_hallii UniRef90_R6G8M7 Cluster: Triosephosphate isomerase 0.11 0.0170 6.2E-01 8.0E-01 -0.1217 1.1E-01 -0.0144 4.7E-01 -0.1201 5.1E-02 0.0340 4.3E-01 Eubacterium_hallii UniRef90_R6FYN6 Cluster: Ketol-acid reductoisomerase (NADP(+)) 0.12 -0.0147 6.3E-01 8.1E-01 -0.0507 4.6E-01 0.0091 6.2E-01 0.0827 1.6E-01 0.0871 2.8E-02 Eubacterium_hallii UniRef90_D4LLG0 Cluster: Choloylglycine hydrolase 0.16 0.0051 6.4E-01 8.1E-01 -0.0106 6.7E-01 -0.0005 9.4E-01 0.0566 5.2E-03 -0.0083 5.5E-01 Eubacterium_hallii UniRef90_C0EU54 Cluster: Transposase, IS605 family (Fragment) 0.12 -0.0069 6.5E-01 8.2E-01 -0.0509 1.3E-01 -0.0088 3.3E-01 -0.0111 7.0E-01 -0.0161 4.1E-01 Eubacterium_hallii UniRef90_R6GBJ7 Cluster: Protein RecA 0.10 0.0130 6.5E-01 8.2E-01 -0.0184 7.7E-01 -0.0113 5.1E-01 0.0433 4.1E-01 -0.0086 8.2E-01 Eubacterium_hallii UniRef90_R6FZA8 Cluster: TPM_phosphatase domain-containing protein 0.11 -0.0142 6.6E-01 8.2E-01 -0.1422 4.2E-02 -0.0275 1.5E-01 -0.0347 5.7E-01 0.0273 5.1E-01 Eubacterium_hallii UniRef90_R5GAN1 Cluster: Propanediol dehydratase medium subunit 0.24 0.0267 6.7E-01 8.3E-01 -0.1036 4.5E-01 -0.0369 3.2E-01 0.0635 5.9E-01 0.1500 6.1E-02 54

Supplementary Data 3b UniRef90 Family Plasma TMAO Red meat Red meat Choline Choline Species Cluster Name Detection member ID Rate Effect P FDR Effect P Effect P Effect P Effect P Eubacterium_hallii UniRef90_R6FYH7 Cluster: L-2-hydroxyglutarate oxidase LhgO 0.24 0.0208 6.8E-01 8.3E-01 -0.2698 1.6E-02 -0.0474 1.1E-01 0.0227 8.1E-01 0.0098 8.8E-01 Eubacterium_hallii UniRef90_C4Z770 Cluster: Flavodoxin family protein 0.14 0.0029 6.8E-01 8.3E-01 -0.0040 8.0E-01 -0.0006 8.8E-01 0.0103 4.4E-01 0.0024 7.9E-01 Eubacterium_hallii UniRef90_R5G748 Cluster: Propanediol dehydratase 0.28 0.0234 6.9E-01 8.4E-01 -0.2573 4.7E-02 -0.0637 7.0E-02 -0.0564 6.1E-01 0.0117 8.8E-01 Eubacterium_hallii UniRef90_C4Z797 Cluster: UPF0246 protein ERS852406_00003 0.15 -0.0039 6.9E-01 8.4E-01 0.0119 5.7E-01 -0.0037 5.2E-01 0.0370 3.9E-02 0.0083 5.0E-01 Eubacterium_hallii UniRef90_R6G6M2 Cluster: Phosphotransferase system, mannose/fructose/sorbose family IID 0.10 0.0104 7.1E-01 8.5E-01 -0.1064 8.3E-02 -0.0087 6.0E-01 -0.0377 4.8E-01 0.0382 2.9E-01 component Eubacterium_hallii UniRef90_B0NYL3 Cluster: Transposase, IS605 OrfB family 0.15 0.0088 7.1E-01 8.5E-01 -0.0963 6.7E-02 -0.0209 1.4E-01 -0.0140 7.5E-01 -0.0107 7.3E-01 Eubacterium_hallii UniRef90_D4J4D9 Cluster: Transcriptional regulatory protein YycF 0.12 -0.0020 7.1E-01 8.5E-01 0.0052 6.7E-01 -0.0018 5.9E-01 -0.0125 2.2E-01 0.0019 7.8E-01 Eubacterium_hallii UniRef90_R6G1I8 Cluster: GGGtGRT protein 0.28 0.0186 7.2E-01 8.6E-01 -0.0204 8.6E-01 0.0029 9.2E-01 0.0779 4.2E-01 0.0839 2.0E-01 Eubacterium_hallii UniRef90_R6GVH7 Cluster: Phosphate acetyltransferase 0.19 -0.0124 7.4E-01 8.7E-01 -0.0261 7.6E-01 -0.0100 6.5E-01 0.0169 8.1E-01 0.0525 2.7E-01 Eubacterium_hallii UniRef90_R5G6M4 Cluster: Propanediol dehydratase small subunit 0.23 0.0235 7.4E-01 8.7E-01 -0.2759 8.7E-02 -0.0220 6.1E-01 0.0133 9.2E-01 0.0531 5.7E-01 Eubacterium_hallii UniRef90_C0F0C5 Cluster: Carbon monoxide dehydrogenase 0.14 -0.0077 7.5E-01 8.8E-01 -0.0179 7.3E-01 -0.0018 9.0E-01 0.0338 4.5E-01 0.0223 4.6E-01 Eubacterium_hallii UniRef90_R6G8X8 Cluster: Carbon dioxide concentrating mechanism protein CcmL 0.14 0.0158 7.5E-01 8.8E-01 -0.0960 3.8E-01 -0.0218 4.6E-01 0.0615 5.0E-01 0.0040 9.5E-01 Eubacterium_hallii UniRef90_R5GNL7 Cluster: FAD-dependent oxidoreductase 0.22 -0.0155 7.6E-01 8.8E-01 -0.1012 3.7E-01 -0.0401 1.8E-01 -0.0206 8.3E-01 0.0496 4.4E-01 Eubacterium_hallii UniRef90_R6GAZ2 Cluster: ABC transporter, solute-binding protein 0.14 -0.0098 7.6E-01 8.8E-01 -0.0832 2.5E-01 -0.0015 9.4E-01 -0.0179 7.7E-01 0.0316 4.4E-01 Eubacterium_hallii UniRef90_R6GUQ5 Cluster: ATP-dependent zinc metalloprotease FtsH 0.11 -0.0065 7.6E-01 8.8E-01 -0.0485 3.1E-01 -0.0015 9.0E-01 -0.0256 5.3E-01 0.0088 7.5E-01 Eubacterium_hallii UniRef90_R6FZN4 Cluster: Ribulokinase 0.18 0.0096 7.7E-01 8.8E-01 -0.0082 9.1E-01 -0.0163 3.9E-01 -0.0153 8.0E-01 -0.0021 9.6E-01 Eubacterium_hallii UniRef90_R6G9N2 Cluster: DNA gyrase subunit B 0.11 -0.0056 7.7E-01 8.8E-01 0.0044 9.2E-01 -0.0074 5.2E-01 0.0156 6.8E-01 0.0121 6.3E-01 Eubacterium_hallii UniRef90_R6G0Y8 Cluster: Methylmalonyl-CoA carboxyltransferase 5S subunit 0.12 0.0072 7.7E-01 8.8E-01 -0.0047 9.3E-01 -0.0085 5.6E-01 -0.0716 1.2E-01 0.0220 4.9E-01 Eubacterium_hallii UniRef90_R6FXW8 Cluster: NADH peroxidase 0.18 0.0165 7.8E-01 8.9E-01 -0.1519 2.5E-01 -0.0472 1.9E-01 -0.0077 9.4E-01 0.0826 2.8E-01 Eubacterium_hallii UniRef90_R6G7T3 Cluster: D-ribose ABC transporter substrate-binding protein 0.19 -0.0146 7.9E-01 8.9E-01 -0.1588 2.1E-01 -0.0169 6.1E-01 0.0493 6.5E-01 0.1244 8.1E-02 Eubacterium_hallii UniRef90_C4Z954 Cluster: Glyceraldehyde-3-phosphate dehydrogenase 0.28 0.0143 8.1E-01 9.0E-01 -0.0800 5.5E-01 -0.0259 4.7E-01 0.0184 8.7E-01 0.0831 2.8E-01 Eubacterium_hallii UniRef90_R5GCT4 Cluster: Phosphoglucomutase (Alpha-D-glucose-1,6-bisphosphate- 0.14 0.0073 8.1E-01 9.0E-01 -0.0983 1.5E-01 -0.0235 2.0E-01 -0.0681 2.5E-01 0.0169 6.7E-01 Eubacterium_hallii UniRef90_R5GAU3 Cluster:dependent) Serine/threonine transporter SstT 0.12 0.0066 8.3E-01 9.1E-01 -0.0951 1.5E-01 -0.0301 8.8E-02 -0.0846 1.1E-01 -0.0080 8.3E-01 Eubacterium_hallii UniRef90_R5GJN1 Cluster: Glutamine ABC transporter substrate-binding protein 0.10 -0.0074 8.3E-01 9.1E-01 0.0236 7.7E-01 0.0081 7.0E-01 0.0615 3.7E-01 0.0682 1.3E-01 Eubacterium_hallii UniRef90_R6G8V1 Cluster: Probable cytosol aminopeptidase 0.11 0.0056 8.3E-01 9.1E-01 -0.0823 1.5E-01 -0.0116 4.6E-01 -0.0601 2.2E-01 0.0208 5.4E-01 Eubacterium_hallii UniRef90_R6G316 Cluster: Glycerol-1-phosphate dehydrogenase [NAD(P)+] 0.11 -0.0045 8.4E-01 9.2E-01 -0.0147 7.7E-01 -0.0130 3.4E-01 0.0105 8.0E-01 0.0081 7.8E-01 Eubacterium_hallii UniRef90_G2T4G4 Cluster: GNAT family acetyltransferase 0.17 -0.0032 8.5E-01 9.2E-01 -0.0439 2.4E-01 -0.0100 3.2E-01 0.0505 1.1E-01 0.0075 7.3E-01 Eubacterium_hallii UniRef90_R6G0V9 Cluster: Chaperone protein DnaK 0.23 0.0061 8.5E-01 9.2E-01 0.0730 3.1E-01 -0.0201 3.0E-01 0.0188 7.6E-01 0.0274 5.2E-01 Eubacterium_hallii UniRef90_R6G887 Cluster: Electron transfer flavoprotein small subunit 0.29 0.0114 8.6E-01 9.2E-01 -0.0006 1.0E+00 -0.0268 4.6E-01 -0.0502 6.6E-01 0.0484 5.4E-01 Eubacterium_hallii UniRef90_R5GNB7 Cluster: 4-hydroxy-3-methylbut-2-enyl diphosphate reductase 0.15 -0.0060 8.6E-01 9.2E-01 -0.0459 5.5E-01 -0.0164 4.2E-01 -0.0424 5.1E-01 0.0350 4.3E-01 Eubacterium_hallii UniRef90_R5GIS7 Cluster: Phosphoenolpyruvate carboxykinase (ATP) 0.10 0.0045 8.6E-01 9.3E-01 0.0173 7.7E-01 -0.0195 2.0E-01 0.0026 9.6E-01 0.0050 8.8E-01 Eubacterium_hallii UniRef90_C0EXZ8 Cluster: HPr kinase/phosphorylase 0.11 -0.0031 8.7E-01 9.3E-01 0.0188 6.4E-01 -0.0078 4.7E-01 -0.0120 7.3E-01 0.0574 1.3E-02 Eubacterium_hallii UniRef90_R5GDU0 Cluster: GTP pyrophosphokinase family protein 0.15 0.0061 8.7E-01 9.3E-01 -0.0330 7.0E-01 0.0008 9.7E-01 0.0501 4.9E-01 0.0369 4.5E-01 Eubacterium_hallii UniRef90_R6GVJ1 Cluster: Elongation factor G 0.13 -0.0041 8.8E-01 9.3E-01 -0.0675 2.6E-01 -0.0325 4.4E-02 -0.0113 8.3E-01 -0.0056 8.7E-01 Eubacterium_hallii UniRef90_R6GY12 Cluster: Transposase and inactivated derivatives 0.14 0.0037 8.8E-01 9.3E-01 0.0356 5.3E-01 0.0034 8.2E-01 0.0606 1.9E-01 0.0294 3.6E-01 Eubacterium_hallii UniRef90_R5GEF0 Cluster: Glutamate dehydrogenase 0.11 0.0033 8.9E-01 9.4E-01 -0.0388 4.5E-01 -0.0023 8.7E-01 -0.0123 7.8E-01 0.0185 5.3E-01 Eubacterium_hallii UniRef90_R5P2I7 Cluster: 30S ribosomal protein S7 0.14 0.0045 9.0E-01 9.4E-01 0.0199 8.0E-01 -0.0020 9.2E-01 -0.0068 9.2E-01 0.0482 2.9E-01 Eubacterium_hallii UniRef90_R5GB28 Cluster: Electron transfer flavoprotein FAD-binding domain protein 0.24 -0.0071 9.0E-01 9.4E-01 -0.1517 2.2E-01 -0.0514 1.1E-01 -0.0341 7.4E-01 -0.0120 8.6E-01 Eubacterium_hallii UniRef90_R6GCB1 Cluster: Tetratricopeptide repeat protein 0.11 0.0035 9.0E-01 9.4E-01 -0.0211 7.3E-01 0.0135 4.1E-01 0.0290 5.8E-01 0.0273 4.4E-01 Eubacterium_hallii UniRef90_C0EXN0 Cluster: BIG2 domain-containing protein 0.10 -0.0034 9.0E-01 9.4E-01 -0.0939 1.5E-01 -0.0121 4.8E-01 0.0646 2.4E-01 -0.0035 9.3E-01 Eubacterium_hallii UniRef90_R5GD71 Cluster: 50S ribosomal protein L2 0.10 0.0034 9.1E-01 9.5E-01 -0.0160 8.2E-01 -0.0101 5.8E-01 0.0121 8.4E-01 0.0050 9.0E-01 Eubacterium_hallii UniRef90_R6FXV2 Cluster: LexA repressor 0.11 0.0034 9.4E-01 9.6E-01 0.0224 8.2E-01 0.0091 7.3E-01 -0.0105 9.0E-01 0.0322 5.7E-01 Eubacterium_hallii UniRef90_R6G9S7 Cluster: DNA-directed RNA polymerase subunit alpha 0.13 -0.0020 9.5E-01 9.7E-01 -0.0189 7.9E-01 0.0067 7.3E-01 -0.0568 3.5E-01 0.0205 6.2E-01 Eubacterium_hallii UniRef90_R6G858 Cluster: Carbon dioxide-concentrating mechanism protein CcmK homolog 2 0.24 -0.0032 9.6E-01 9.8E-01 -0.2173 1.1E-01 -0.0237 5.2E-01 -0.0377 7.4E-01 0.0964 2.2E-01 Eubacterium_hallii UniRef90_R6GCU1 Cluster: Acetate kinase 0.12 0.0015 9.6E-01 9.8E-01 -0.1320 4.7E-02 -0.0264 1.3E-01 -0.0036 9.5E-01 0.0232 5.4E-01 Eubacterium_hallii UniRef90_R5GCS8 Cluster: Dihydroxyacetone kinase subunit DhaK 0.18 0.0022 9.6E-01 9.8E-01 -0.2048 5.9E-02 -0.0559 5.6E-02 -0.0501 5.9E-01 0.0356 5.7E-01 Eubacterium_hallii UniRef90_R5GPA4 Cluster: ATP synthase subunit alpha 0.14 -0.0010 9.7E-01 9.8E-01 -0.0546 2.7E-01 -0.0006 9.6E-01 0.0068 8.7E-01 0.0403 1.6E-01 Eubacterium_hallii UniRef90_R6GUR3 Cluster: EIICBA-Mtl 0.10 -0.0008 9.7E-01 9.8E-01 0.0284 5.3E-01 -0.0093 4.5E-01 0.0382 3.3E-01 0.0273 3.0E-01 Eubacterium_hallii UniRef90_R5TK71 Cluster: 30S ribosomal protein S12 0.13 0.0017 9.7E-01 9.8E-01 0.0047 9.6E-01 -0.0068 7.9E-01 0.0074 9.3E-01 0.0939 9.6E-02 Eubacterium_hallii UniRef90_D4LLF7 Cluster: Cardiolipin synthase 0.11 -0.0002 9.8E-01 9.9E-01 0.0004 9.8E-01 0.0003 9.2E-01 0.0297 9.1E-03 -0.0160 3.4E-02 Eubacterium_hallii UniRef90_C4Z798 Cluster: Thioredoxin domain-containing protein 0.14 -0.0003 9.8E-01 9.9E-01 -0.0433 1.2E-01 0.0030 6.9E-01 0.0050 8.3E-01 -0.0171 2.9E-01 Eubacterium_hallii UniRef90_C0EZA7 Cluster: Transposase, IS605 OrfB family 0.14 0.0002 9.9E-01 9.9E-01 -0.0147 7.3E-01 -0.0113 3.2E-01 -0.0251 4.8E-01 -0.0167 5.0E-01 Roseburia_hominis UniRef90_G2SXM9 Cluster: 50S ribosomal protein L19 0.14 0.2524 5.1E-05 6.9E-02 -0.0716 6.1E-01 -0.0144 7.0E-01 0.0795 5.0E-01 0.0725 3.6E-01 Roseburia_hominis UniRef90_R5TR32 Cluster: 30S ribosomal protein S17 0.14 0.2773 8.5E-05 5.8E-02 -0.0359 8.2E-01 0.0056 8.9E-01 0.0763 5.6E-01 0.1320 1.5E-01 Roseburia_hominis UniRef90_G2SXP9 Cluster: Putative Zn-finger-like protein, possible nucleic acid binding protein 0.18 0.3153 9.3E-05 4.2E-02 -0.2920 1.1E-01 -0.0530 2.6E-01 0.3084 4.3E-02 0.2383 1.8E-02 Roseburia_hominis UniRef90_G2SZJ3 Cluster: Vancomycin resistance protein 0.12 0.1372 1.4E-04 4.9E-02 -0.0293 7.2E-01 -0.0049 8.2E-01 0.0287 6.7E-01 0.1050 2.3E-02 Roseburia_hominis UniRef90_G2T0V5 Cluster: Extracellular solute-binding protein family 1 0.13 0.1394 3.2E-04 7.3E-02 -0.0404 6.5E-01 -0.0260 2.6E-01 0.0744 3.2E-01 0.0717 1.6E-01 Roseburia_hominis UniRef90_G2T1M4 Cluster: PTS system, N-acetylglucosamine-specific IIBC component 0.15 0.1609 3.4E-04 6.6E-02 -0.2108 3.3E-02 -0.0666 1.2E-02 -0.0929 2.7E-01 0.0091 8.7E-01 Roseburia_hominis UniRef90_G2T3E6 Cluster: Flagellar motor switch protein 0.17 0.2222 4.0E-04 6.8E-02 -0.0186 9.0E-01 0.0283 4.4E-01 0.2050 8.0E-02 0.1109 1.6E-01 Roseburia_hominis UniRef90_R5HLA1 Cluster: 50S ribosomal protein L20 0.22 0.2684 5.1E-04 7.7E-02 -0.3430 4.4E-02 -0.0030 9.5E-01 0.1093 4.4E-01 0.2599 7.0E-03 Roseburia_hominis UniRef90_G2T4N2 Cluster: 30S ribosomal protein S4 0.20 0.2758 5.5E-04 7.5E-02 -0.1455 4.1E-01 -0.0313 5.1E-01 0.0411 7.8E-01 0.2578 1.1E-02 Roseburia_hominis UniRef90_G2SXR6 Cluster: Peptidase, M24 family protein 0.15 0.1302 6.8E-04 8.4E-02 -0.1083 2.1E-01 -0.0316 1.7E-01 0.0155 8.3E-01 0.0569 2.5E-01 Roseburia_hominis UniRef90_C4ZBU6 Cluster: DNA-directed RNA polymerase subunit alpha 0.22 0.2361 8.2E-04 8.6E-02 -0.1618 3.0E-01 -0.0428 3.0E-01 0.0120 9.3E-01 0.0927 3.0E-01 Roseburia_hominis UniRef90_D4KRR1 Cluster: Predicted metal-binding protein related to the C-terminal domain 0.12 0.1576 1.1E-03 1.1E-01 -0.2178 4.2E-02 -0.0339 2.4E-01 0.0083 9.3E-01 0.0969 1.1E-01 of SecA Roseburia_hominis UniRef90_G2T3E3 Cluster: Chemotaxis protein 0.16 0.1724 1.2E-03 1.1E-01 -0.0768 5.2E-01 0.0142 6.5E-01 0.1023 2.9E-01 0.0758 2.6E-01 Roseburia_hominis UniRef90_R5I2D5 Cluster: ATP synthase subunit c 0.14 0.1734 1.2E-03 1.0E-01 -0.1481 2.1E-01 -0.0538 9.2E-02 0.1239 2.1E-01 0.0247 7.2E-01 Roseburia_hominis UniRef90_G2T5M5 Cluster: 50S ribosomal protein L29 0.17 0.2292 1.3E-03 1.0E-01 -0.1109 4.9E-01 -0.0376 3.7E-01 0.2468 6.9E-02 0.1171 2.0E-01 Roseburia_hominis UniRef90_R6AU41 Cluster: 50S ribosomal protein L10 0.17 0.1984 1.9E-03 1.4E-01 -0.1263 3.7E-01 -0.0390 2.9E-01 0.2134 7.1E-02 0.1622 4.0E-02 Roseburia_hominis UniRef90_G2T5U0 Cluster: Putative spore cortex-lytic enzyme 0.17 0.1829 1.9E-03 1.4E-01 -0.1652 2.2E-01 -0.0451 1.9E-01 0.0346 7.6E-01 0.0503 5.0E-01 Roseburia_hominis UniRef90_G2T603 Cluster: ATP synthase subunit beta 0.23 0.1858 2.0E-03 1.3E-01 -0.1648 2.2E-01 -0.0145 6.8E-01 -0.0328 7.7E-01 0.0598 4.3E-01 Roseburia_hominis UniRef90_G2T275 Cluster: Glutamine-dependent NAD(+) synthetase 0.11 0.0778 2.1E-03 1.3E-01 -0.1037 5.9E-02 -0.0218 1.3E-01 -0.0728 1.2E-01 0.0021 9.5E-01 Roseburia_hominis UniRef90_G2T1W2 Cluster: Sarcosine oxidase alpha subunit 0.12 0.1123 2.2E-03 1.3E-01 -0.0809 3.2E-01 -0.0141 5.1E-01 -0.0221 7.5E-01 0.0793 9.0E-02 Roseburia_hominis UniRef90_G2SZK6 Cluster: Flagellin 0.30 0.3962 2.3E-03 1.3E-01 -0.1622 5.8E-01 0.0256 7.3E-01 0.0556 8.2E-01 0.2483 1.2E-01 Roseburia_hominis UniRef90_G2T001 Cluster: Tim44 domain-containing protein 0.10 0.0996 2.4E-03 1.4E-01 -0.1258 8.6E-02 -0.0169 3.9E-01 -0.0287 6.4E-01 0.0218 6.0E-01 Roseburia_hominis UniRef90_G2T2F0 Cluster: Putative hemolysin-related protein 0.12 0.1244 2.5E-03 1.4E-01 -0.1096 2.4E-01 -0.0359 1.4E-01 0.0439 5.7E-01 0.0794 1.3E-01 Roseburia_hominis UniRef90_G2T413 Cluster: Putative mutarotase 0.14 0.1235 2.7E-03 1.4E-01 -0.0366 6.9E-01 0.0196 4.1E-01 -0.0282 7.1E-01 0.1013 4.7E-02 Roseburia_hominis UniRef90_G2T3C0 Cluster: Two-component system response regulator 0.12 0.1185 2.9E-03 1.4E-01 0.0053 9.5E-01 -0.0279 2.2E-01 -0.0407 5.9E-01 0.0661 1.8E-01 Roseburia_hominis UniRef90_G2SX60 Cluster: Methyl-accepting transducer domain-containing protein 0.12 0.1144 3.0E-03 1.5E-01 -0.1414 9.9E-02 -0.0031 8.9E-01 -0.0153 8.3E-01 -0.0141 7.7E-01 Roseburia_hominis UniRef90_D4KXR7 Cluster: 30S ribosomal protein S1 0.20 0.2137 3.1E-03 1.5E-01 -0.0902 5.8E-01 0.0301 4.8E-01 0.0295 8.3E-01 0.1637 7.0E-02 Roseburia_hominis UniRef90_G2SXE9 Cluster: Extracellular solute-binding protein family 1 0.21 0.2337 3.1E-03 1.4E-01 -0.1545 3.8E-01 -0.0260 5.7E-01 -0.0012 9.9E-01 0.0943 3.4E-01 Roseburia_hominis UniRef90_R5HLZ1 Cluster: Protein translocase subunit SecY 0.20 0.2143 3.2E-03 1.4E-01 -0.1223 4.6E-01 0.0176 6.8E-01 0.1593 2.4E-01 0.1096 2.3E-01 Roseburia_hominis UniRef90_G2SZE6 Cluster: FAD-dependent oxidoreductase 0.19 0.2320 3.5E-03 1.4E-01 -0.0931 6.0E-01 -0.0320 4.9E-01 0.1230 4.1E-01 0.0700 4.8E-01 Roseburia_hominis UniRef90_G2SXW6 Cluster: Beta-N-acetylhexosaminidase 0.10 0.0836 3.6E-03 1.4E-01 -0.0883 1.6E-01 -0.0127 4.6E-01 0.0413 4.3E-01 0.0234 5.3E-01 Roseburia_hominis UniRef90_D4JA60 Cluster: HTH cro/C1-type domain-containing protein 0.17 0.0453 4.1E-03 1.6E-01 -0.0316 3.6E-01 -0.0232 1.3E-02 0.0145 6.2E-01 0.0145 4.7E-01 Roseburia_hominis UniRef90_G2SXE6 Cluster: ABC transporter permease 0.12 0.1262 4.1E-03 1.5E-01 -0.1048 2.7E-01 -0.0116 6.5E-01 -0.0421 6.0E-01 0.0510 3.6E-01 Roseburia_hominis UniRef90_G2T3M9 Cluster: BMP family ABC transporter substrate-binding protein 0.21 0.2062 4.2E-03 1.5E-01 -0.2220 1.7E-01 -0.0676 1.0E-01 0.1063 4.3E-01 0.0665 4.6E-01 Roseburia_hominis UniRef90_D4L489 Cluster: Butyryl-CoA:acetate CoA-transferase 0.16 0.1331 4.7E-03 1.6E-01 -0.0691 5.1E-01 -0.0365 1.9E-01 0.1024 2.4E-01 0.0741 2.1E-01 Roseburia_hominis UniRef90_G2SZE5 Cluster: Sarcosine oxidase alpha subunit 0.19 0.2157 4.9E-03 1.6E-01 -0.1450 4.0E-01 -0.0191 6.7E-01 0.1160 4.2E-01 0.1455 1.3E-01 Roseburia_hominis UniRef90_C4ZBS3 Cluster: 30S ribosomal protein S19 0.21 0.1918 5.1E-03 1.7E-01 0.1094 4.7E-01 -0.0182 6.5E-01 0.0793 5.4E-01 0.1245 1.5E-01 Roseburia_hominis UniRef90_G2T1W3 Cluster: Glycerol-3-phosphate dehydrogenase GlpA 0.11 0.0915 5.3E-03 1.7E-01 -0.1681 2.0E-02 -0.0198 3.1E-01 -0.0070 9.1E-01 0.0510 2.2E-01 Roseburia_hominis UniRef90_G2SXD3 Cluster: Transcriptional regulator 0.17 0.1212 6.3E-03 1.9E-01 -0.0422 6.6E-01 -0.0074 7.8E-01 0.0300 7.1E-01 0.1235 2.5E-02 Roseburia_hominis UniRef90_G2SX97 Cluster: Electron transfer flavoprotein subunit beta/FixA family protein 0.14 0.1395 6.3E-03 1.9E-01 0.0286 8.1E-01 0.0067 8.3E-01 0.0856 3.7E-01 0.0470 4.7E-01 55

Supplementary Data 3b UniRef90 Family Plasma TMAO Red meat Red meat Choline Choline Species Cluster Name Detection member ID Rate Effect P FDR Effect P Effect P Effect P Effect P Roseburia_hominis UniRef90_C4ZBS4 Cluster: 50S ribosomal protein L22 0.21 0.2161 6.6E-03 1.9E-01 -0.0361 8.4E-01 -0.0179 7.0E-01 0.0363 8.0E-01 0.1716 8.9E-02 Roseburia_hominis UniRef90_G2SXJ3 Cluster: Cysteine--tRNA ligase 0.12 0.0652 6.9E-03 1.9E-01 -0.0283 5.9E-01 -0.0216 1.4E-01 0.0010 9.8E-01 -0.0002 9.9E-01 Roseburia_hominis UniRef90_G2T4S2 Cluster: HTH cro/C1-type domain-containing protein 0.11 0.0432 7.0E-03 1.9E-01 0.0691 4.7E-02 0.0262 7.0E-03 0.0542 6.9E-02 -0.0185 3.9E-01 Roseburia_hominis UniRef90_G2T5W2 Cluster: Flagellin 0.19 0.1290 7.1E-03 1.9E-01 -0.1824 8.6E-02 -0.0436 1.2E-01 0.0472 6.0E-01 0.0430 4.7E-01 Roseburia_hominis UniRef90_C4Z929 Cluster: 30S ribosomal protein S16 0.14 0.1709 7.6E-03 2.0E-01 -0.1932 1.8E-01 -0.0601 1.1E-01 0.1342 2.7E-01 0.1196 1.4E-01 Roseburia_hominis UniRef90_G2SX98 Cluster: Acyl-CoA dehydrogenase 0.13 0.1323 8.2E-03 2.2E-01 -0.0297 7.9E-01 -0.0070 8.1E-01 -0.0357 7.0E-01 0.1061 9.0E-02 Roseburia_hominis UniRef90_G2SXI1 Cluster: ABC-type sugar transport system, periplasmic component 0.14 0.1108 8.3E-03 2.1E-01 -0.0851 3.5E-01 -0.0469 5.6E-02 0.0638 4.1E-01 -0.0221 6.8E-01 Roseburia_hominis UniRef90_G2T4Z3 Cluster: Single-stranded DNA-binding protein 0.17 0.1736 8.4E-03 2.1E-01 0.0101 9.4E-01 0.0105 7.9E-01 0.2284 6.3E-02 0.1953 2.0E-02 Roseburia_hominis UniRef90_G2T205 Cluster: Carbohydrate ABC transporter permease 0.17 0.1751 9.1E-03 2.3E-01 -0.1762 2.4E-01 -0.0681 8.9E-02 0.1319 2.9E-01 0.1488 8.4E-02 Roseburia_hominis UniRef90_G2SWU5 Cluster: Ribosomal-processing cysteine protease Prp 0.12 0.1646 9.2E-03 2.2E-01 -0.0879 5.4E-01 0.0141 7.1E-01 0.1288 2.8E-01 0.2181 6.5E-03 Roseburia_hominis UniRef90_G2T331 Cluster: N-acetylmuramoyl-L-alanine amidase, C-terminus 0.14 0.1175 9.5E-03 2.3E-01 -0.0236 8.1E-01 -0.0229 3.9E-01 0.0263 7.5E-01 0.0661 2.5E-01 Roseburia_hominis UniRef90_D4JL88 Cluster: 50S ribosomal protein L2 0.24 0.1796 9.6E-03 2.3E-01 -0.2415 1.2E-01 -0.0185 6.5E-01 0.0734 5.7E-01 0.1839 3.8E-02 Roseburia_hominis UniRef90_D4KSU2 Cluster: Acetyl-CoA acetyltransferase 0.24 0.2021 9.7E-03 2.2E-01 -0.3297 6.4E-02 -0.0376 4.1E-01 0.0223 8.8E-01 0.1070 2.7E-01 Roseburia_hominis UniRef90_G2SZZ2 Cluster: Hydrolase Nlp/P60 0.18 0.1487 9.8E-03 2.2E-01 -0.0540 6.7E-01 -0.0156 6.4E-01 0.0832 4.4E-01 0.0766 2.9E-01 Roseburia_hominis UniRef90_R5I0T3 Cluster: Translation initiation factor IF-3 0.15 0.1839 1.0E-02 2.2E-01 -0.2678 9.2E-02 -0.0088 8.3E-01 0.1380 3.0E-01 0.0803 3.6E-01 Roseburia_hominis UniRef90_G2T3F5 Cluster: Flagellar biosynthesis protein FlhG 0.11 0.1068 1.0E-02 2.2E-01 -0.0985 2.9E-01 -0.0208 4.0E-01 -0.0730 3.6E-01 0.0257 6.3E-01 Roseburia_hominis UniRef90_G2T605 Cluster: ATP synthase subunit alpha 0.24 0.1595 1.0E-02 2.2E-01 -0.1256 3.6E-01 -0.0008 9.8E-01 0.0493 6.7E-01 0.2072 8.0E-03 Roseburia_hominis UniRef90_G2T5M2 Cluster: 50S ribosomal protein L24 0.14 0.1968 1.0E-02 2.1E-01 -0.1713 3.2E-01 -0.0098 8.3E-01 0.0462 7.5E-01 0.1285 1.8E-01 Roseburia_hominis UniRef90_G2T074 Cluster: Fe-ADH domain-containing protein 0.22 0.1721 1.1E-02 2.1E-01 -0.1204 4.3E-01 -0.0483 2.2E-01 0.1396 2.7E-01 -0.0036 9.7E-01 Roseburia_hominis UniRef90_G2T5B3 Cluster: Rod shape-determining protein MreB 0.17 0.1250 1.1E-02 2.2E-01 -0.2597 1.7E-02 -0.0355 2.2E-01 0.0411 6.6E-01 0.0931 1.3E-01 Roseburia_hominis UniRef90_R6BEH1 Cluster: Ribonuclease J 0.16 0.1006 1.1E-02 2.2E-01 -0.0525 5.5E-01 -0.0134 5.7E-01 -0.0802 2.9E-01 0.0418 4.1E-01 Roseburia_hominis UniRef90_G2T0P2 Cluster: Extracellular solute-binding protein 0.22 0.1780 1.3E-02 2.3E-01 0.0304 8.5E-01 -0.0315 4.5E-01 0.0672 6.2E-01 0.0648 4.7E-01 Roseburia_hominis UniRef90_G2SWV8 Cluster: Cytidylate kinase 0.13 0.1310 1.3E-02 2.3E-01 -0.1887 1.1E-01 -0.0225 4.7E-01 0.1389 1.7E-01 0.0752 2.6E-01 Roseburia_hominis UniRef90_G2T5T9 Cluster: Peptidase 0.20 0.1295 1.4E-02 2.4E-01 -0.2213 5.8E-02 -0.0247 4.2E-01 0.0034 9.7E-01 0.1076 1.0E-01 Roseburia_hominis UniRef90_G2T2Q7 Cluster: Sugars ABC transporter substrate-binding protein 0.21 0.1865 1.4E-02 2.4E-01 -0.0681 6.8E-01 0.0199 6.5E-01 0.0465 7.4E-01 0.1998 3.4E-02 Roseburia_hominis UniRef90_D4KZI6 Cluster: Phosphate acyltransferase 0.13 0.1032 1.4E-02 2.4E-01 -0.1841 4.9E-02 -0.0394 1.0E-01 0.0831 2.8E-01 0.0455 3.8E-01 Roseburia_hominis UniRef90_G2T542 Cluster: Alpha/beta hydrolase fold protein 0.11 0.0958 1.4E-02 2.3E-01 -0.1885 2.9E-02 -0.0068 7.7E-01 -0.0480 5.1E-01 0.0350 4.8E-01 Roseburia_hominis UniRef90_G2T4E0 Cluster: Ribose-phosphate diphosphokinase 0.13 0.0842 1.4E-02 2.3E-01 -0.1035 1.8E-01 -0.0159 4.4E-01 0.0012 9.8E-01 0.0712 1.1E-01 Roseburia_hominis UniRef90_C4Z2U0 Cluster: 50S ribosomal protein L14 0.22 0.1737 1.5E-02 2.4E-01 0.0372 8.1E-01 -0.0364 3.8E-01 -0.0092 9.5E-01 0.1587 7.8E-02 Roseburia_hominis UniRef90_G2T3E9 Cluster: Flagellar biosynthetic protein FliP 0.17 0.1424 1.5E-02 2.4E-01 -0.0186 8.8E-01 0.0027 9.4E-01 0.1114 3.0E-01 0.1151 1.2E-01 Roseburia_hominis UniRef90_C4ZD46 Cluster: 60 kDa chaperonin 0.19 0.1061 1.5E-02 2.4E-01 -0.0264 7.8E-01 -0.0028 9.1E-01 0.0365 6.5E-01 0.0349 5.2E-01 Roseburia_hominis UniRef90_G2SZR6 Cluster: Transmembrane protein 0.13 0.0949 1.6E-02 2.5E-01 -0.0463 6.0E-01 -0.0083 7.2E-01 -0.0034 9.6E-01 0.0576 2.5E-01 Roseburia_hominis UniRef90_G2T3H8 Cluster: Ribosome-recycling factor 0.11 0.1087 1.7E-02 2.6E-01 -0.1832 7.0E-02 -0.0534 4.7E-02 0.0141 8.7E-01 0.0908 1.1E-01 Roseburia_hominis UniRef90_G2SWV4 Cluster: 1-acyl-sn-glycerol-3-phosphate acyltransferase 0.10 0.0776 1.8E-02 2.6E-01 -0.0316 6.7E-01 0.0031 8.7E-01 0.0591 3.3E-01 0.0789 5.7E-02 Roseburia_hominis UniRef90_G2T4G4 Cluster: GNAT family acetyltransferase 0.16 0.0275 1.9E-02 2.7E-01 -0.0062 8.1E-01 0.0026 7.1E-01 0.0054 8.1E-01 0.0211 1.6E-01 Roseburia_hominis UniRef90_G2SZK0 Cluster: Flagellar assembly factor FliW 0.10 0.1070 1.9E-02 2.7E-01 -0.1635 1.1E-01 -0.0354 1.9E-01 -0.0177 8.3E-01 0.0035 9.5E-01 Roseburia_hominis UniRef90_G2T0P4 Cluster: Binding-protein-dependent transport systems inner membrane 0.13 0.0702 2.0E-02 2.7E-01 -0.1580 1.8E-02 -0.0427 1.7E-02 -0.0475 4.0E-01 0.0274 4.8E-01 component Roseburia_hominis UniRef90_D4KPE8 Cluster: 50S ribosomal protein L13 0.15 0.1360 2.0E-02 2.7E-01 -0.0436 7.4E-01 -0.0431 2.1E-01 0.1276 2.5E-01 0.1068 1.5E-01 Roseburia_hominis UniRef90_D4JN76 Cluster: Site-specific integrase 0.19 0.0207 2.0E-02 2.7E-01 -0.0085 6.7E-01 0.0061 2.5E-01 -0.0067 6.6E-01 0.0055 6.3E-01 Roseburia_hominis UniRef90_G2SZK2 Cluster: Uncharacterized flagellar protein FlaG 0.16 0.1592 2.2E-02 2.9E-01 -0.0719 6.5E-01 -0.0256 5.3E-01 0.1333 3.1E-01 0.0433 6.2E-01 Roseburia_hominis UniRef90_D4KN07 Cluster: UPF0109 protein BIV16_04340 0.11 0.1251 2.2E-02 2.8E-01 -0.0271 8.2E-01 -0.0022 9.5E-01 0.0798 4.3E-01 0.0951 1.7E-01 Roseburia_hominis UniRef90_G2T3D8 Cluster: Flagellar hook-length control protein FliK 0.21 0.1662 2.2E-02 2.8E-01 -0.0273 8.7E-01 -0.0254 5.5E-01 -0.0020 9.9E-01 0.0025 9.8E-01 Roseburia_hominis UniRef90_G2SZJ9 Cluster: Flagellin 0.19 0.1198 2.2E-02 2.8E-01 -0.1573 1.9E-01 -0.0171 5.8E-01 0.1092 2.8E-01 0.1297 5.2E-02 Roseburia_hominis UniRef90_UPI00047C605A Cluster: 50S ribosomal protein L27 0.17 0.1479 2.3E-02 2.9E-01 -0.0355 8.1E-01 -0.0236 5.4E-01 0.1427 2.4E-01 0.0732 3.7E-01 Roseburia_hominis UniRef90_D4KSU4 Cluster: Acyl-CoA dehydrogenase, short-chain specific 0.24 0.1615 2.3E-02 2.9E-01 -0.0655 6.8E-01 -0.0440 3.0E-01 0.0192 8.8E-01 0.0956 2.9E-01 Roseburia_hominis UniRef90_G2SZK4 Cluster: Flagellar secretion chaperone FliS 0.13 0.1344 2.3E-02 2.9E-01 -0.1355 3.1E-01 -0.0553 1.1E-01 0.1301 2.5E-01 0.0593 4.3E-01 Roseburia_hominis UniRef90_G2T1I0 Cluster: Rod shape-determining protein MreB 0.11 0.0883 2.3E-02 2.8E-01 0.0526 5.4E-01 -0.0195 3.9E-01 0.0256 7.2E-01 0.0552 2.6E-01 Roseburia_hominis UniRef90_O52836 Cluster: Tetracycline resistance protein TetW 0.16 0.0112 2.5E-02 3.0E-01 0.0025 8.4E-01 -0.0011 7.0E-01 -0.0025 8.0E-01 -0.0003 9.7E-01 Roseburia_hominis UniRef90_G2T5W8 Cluster: SH3b domain-containing protein 0.11 0.0542 2.5E-02 3.0E-01 -0.0743 1.8E-01 -0.0101 4.7E-01 0.0154 7.4E-01 0.0474 1.2E-01 Roseburia_hominis UniRef90_G2T2R8 Cluster: Purine nucleoside phosphorylase 0.10 0.0759 2.5E-02 2.9E-01 -0.0808 2.8E-01 0.0003 9.9E-01 0.0641 3.0E-01 0.1010 1.7E-02 Roseburia_hominis UniRef90_C4ZBU2 Cluster: 50S ribosomal protein L36 0.11 0.0840 2.5E-02 2.9E-01 0.0266 7.5E-01 -0.0005 9.8E-01 0.0274 7.0E-01 0.0633 1.9E-01 Roseburia_hominis UniRef90_G2SXW5 Cluster: Methyl-accepting chemotaxis sensory transducer 0.14 0.0943 2.6E-02 2.9E-01 -0.1941 3.5E-02 -0.0266 2.9E-01 -0.0926 2.3E-01 0.0136 8.0E-01 Roseburia_hominis UniRef90_G2T1K7 Cluster: Probable transcriptional regulatory protein RHOM_07835 0.13 0.1049 2.6E-02 2.9E-01 -0.0635 5.5E-01 -0.0453 9.6E-02 0.1203 1.7E-01 0.0537 3.6E-01 Roseburia_hominis UniRef90_G2T3K1 Cluster: Transcription termination/antitermination protein NusA 0.10 0.0654 2.6E-02 2.9E-01 -0.1024 1.1E-01 -0.0252 1.5E-01 -0.0113 8.3E-01 -0.0175 6.4E-01 Roseburia_hominis UniRef90_G2T260 Cluster: ATP-dependent 6-phosphofructokinase 0.13 0.0924 2.6E-02 2.8E-01 -0.1288 1.7E-01 -0.0324 1.9E-01 0.1019 1.9E-01 0.0229 6.6E-01 Roseburia_hominis UniRef90_G2T1Q8 Cluster: DUF3533 domain-containing protein 0.11 0.0605 2.7E-02 2.8E-01 -0.0043 9.4E-01 -0.0172 2.9E-01 0.0129 7.9E-01 -0.0221 5.3E-01 Roseburia_hominis UniRef90_G2T173 Cluster: Elongation factor P 0.14 0.1273 2.7E-02 2.8E-01 -0.1350 2.8E-01 -0.0144 6.7E-01 0.0816 4.4E-01 0.1970 6.5E-03 Roseburia_hominis UniRef90_G2T448 Cluster: LytR_cpsA_psr domain-containing protein 0.16 0.1113 2.8E-02 2.8E-01 -0.2066 6.7E-02 -0.0283 3.3E-01 0.0711 4.5E-01 0.0103 8.7E-01 Roseburia_hominis UniRef90_G2T1Q6 Cluster: Pip phage infection protein-like protein 0.10 0.0529 2.8E-02 2.8E-01 -0.0464 3.8E-01 -0.0141 3.2E-01 -0.0018 9.7E-01 0.0316 3.0E-01 Roseburia_hominis UniRef90_G2SYU2 Cluster: Transposase IS66 0.13 0.0623 2.8E-02 2.8E-01 -0.0426 4.9E-01 -0.0120 4.7E-01 -0.0315 5.5E-01 -0.0114 7.5E-01 Roseburia_hominis UniRef90_G2SX32 Cluster: Cell division protein FtsZ 0.15 0.1026 2.8E-02 2.8E-01 -0.1423 1.8E-01 -0.0494 7.3E-02 0.0597 5.0E-01 0.0126 8.3E-01 Roseburia_hominis UniRef90_G2T2F5 Cluster: LL-diaminopimelate aminotransferase 0.10 0.0664 2.8E-02 2.8E-01 -0.1126 9.3E-02 -0.0218 2.3E-01 0.0218 7.0E-01 0.0492 2.1E-01 Roseburia_hominis UniRef90_G2T5L6 Cluster: 50S ribosomal protein L18 0.16 0.1671 2.8E-02 2.8E-01 -0.2664 1.1E-01 -0.0171 7.0E-01 0.0356 8.0E-01 0.0539 5.8E-01 Roseburia_hominis UniRef90_D4KSN3 Cluster: CTP synthase 0.13 0.0693 2.8E-02 2.7E-01 -0.0622 3.8E-01 -0.0276 1.5E-01 0.0468 4.3E-01 0.0623 1.3E-01 Roseburia_hominis UniRef90_G2T3E1 Cluster: Flagellar basal body protein 0.19 0.1286 2.9E-02 2.7E-01 -0.1902 1.5E-01 -0.0100 7.7E-01 -0.0586 6.0E-01 -0.0423 5.7E-01 Roseburia_hominis UniRef90_G2T3F8 Cluster: Putative CheA signal transduction histidine kinase 0.18 0.1153 2.9E-02 2.7E-01 0.0298 8.0E-01 0.0051 8.7E-01 -0.0292 7.7E-01 0.0920 1.7E-01 Roseburia_hominis UniRef90_G2T3E5 Cluster: Flagellar motor switch protein FliM 0.16 0.1196 2.9E-02 2.7E-01 -0.0599 6.3E-01 0.0012 9.7E-01 0.1341 1.9E-01 0.1404 4.2E-02 Roseburia_hominis UniRef90_R5HJ25 Cluster: Ornithine carbamoyltransferase 0.13 0.0772 3.0E-02 2.7E-01 -0.0751 3.4E-01 -0.0082 7.0E-01 0.0391 5.6E-01 0.0518 2.6E-01 Roseburia_hominis UniRef90_R5HWL3 Cluster: 30S ribosomal protein S8 0.20 0.1561 3.0E-02 2.7E-01 -0.1863 2.5E-01 -0.0219 6.1E-01 -0.0819 5.4E-01 0.0904 3.2E-01 Roseburia_hominis UniRef90_G2SXK4 Cluster: Imidazole glycerol phosphate synthase subunit HisH 0.11 0.0765 3.0E-02 2.7E-01 -0.2105 5.9E-03 -0.0336 1.0E-01 -0.0472 4.7E-01 0.0297 5.1E-01 Roseburia_hominis UniRef90_C4Z9F2 Cluster: Methylmalonyl-CoA carboxyltransferase 5S subunit 0.22 0.1317 3.1E-02 2.7E-01 -0.1635 2.3E-01 -0.0384 2.8E-01 0.0401 7.3E-01 0.0557 4.7E-01 Roseburia_hominis UniRef90_G2SWW7 Cluster: Twitching motility protein PilT 0.11 0.1139 3.1E-02 2.7E-01 -0.0899 4.4E-01 0.0145 6.5E-01 0.1068 2.8E-01 0.0759 2.6E-01 Roseburia_hominis UniRef90_G2SXS1 Cluster: Small ribosomal subunit biogenesis GTPase RsgA 0.10 0.0610 3.3E-02 2.8E-01 -0.0684 2.7E-01 -0.0119 4.7E-01 -0.0048 9.3E-01 0.0508 1.6E-01 Roseburia_hominis UniRef90_G2T330 Cluster: 30S ribosomal protein S15 0.16 0.1698 3.3E-02 2.8E-01 -0.1252 4.8E-01 -0.0450 3.4E-01 -0.0348 8.2E-01 0.0785 4.4E-01 Roseburia_hominis UniRef90_D4KWM4 Cluster: Glutamate synthase [NADPH] small chain 0.12 0.0664 3.4E-02 2.8E-01 -0.0075 9.1E-01 0.0125 5.0E-01 0.0706 2.1E-01 0.0849 3.1E-02 Roseburia_hominis UniRef90_G2T202 Cluster: Purine nucleotide synthesis repressor 0.18 0.1354 3.4E-02 2.8E-01 -0.2180 1.3E-01 -0.0191 6.1E-01 0.1076 3.6E-01 0.1303 1.0E-01 Roseburia_hominis UniRef90_G2T1D6 Cluster: Phosphoserine aminotransferase 0.13 0.0967 3.4E-02 2.8E-01 0.0461 6.4E-01 0.0152 5.8E-01 0.0541 5.2E-01 0.0626 2.8E-01 Roseburia_hominis UniRef90_G2T456 Cluster: Transcriptional regulator 0.13 0.1444 3.4E-02 2.8E-01 -0.2349 1.3E-01 0.0062 8.8E-01 -0.2215 8.6E-02 0.0908 3.0E-01 Roseburia_hominis UniRef90_R6NIE2 Cluster: Electron transfer flavoprotein subunit alpha 0.24 0.1840 3.5E-02 2.8E-01 0.0263 8.9E-01 0.0289 5.7E-01 0.2045 2.1E-01 0.2165 4.5E-02 Roseburia_hominis UniRef90_C4ZBT1 Cluster: 50S ribosomal protein L5 0.22 0.1529 3.6E-02 2.9E-01 -0.0523 7.4E-01 -0.0359 4.0E-01 0.0507 7.1E-01 0.1928 3.8E-02 Roseburia_hominis UniRef90_D4KSF0 Cluster: ATP-dependent Clp protease ATP-binding subunit ClpX 0.12 0.0749 3.6E-02 2.9E-01 -0.1093 1.8E-01 0.0185 3.8E-01 0.0072 9.1E-01 0.0408 3.6E-01 Roseburia_hominis UniRef90_G2T0A3 Cluster: LacI family transcriptional regulator 0.21 0.1767 3.6E-02 2.9E-01 -0.0336 8.6E-01 -0.0140 7.8E-01 -0.0594 7.1E-01 0.0172 8.7E-01 Roseburia_hominis UniRef90_G2SX55 Cluster: Adenylosuccinate synthetase 0.11 0.0666 3.6E-02 2.9E-01 -0.0805 2.6E-01 -0.0235 2.1E-01 -0.0320 6.0E-01 0.0451 2.6E-01 Roseburia_hominis UniRef90_G2T2B6 Cluster: Methyl-accepting transducer domain-containing protein 0.11 0.0607 3.6E-02 2.9E-01 -0.0189 7.7E-01 0.0034 8.5E-01 -0.0057 9.1E-01 0.0559 1.4E-01 Roseburia_hominis UniRef90_G2T200 Cluster: Pyruvate kinase 0.13 0.0734 3.7E-02 2.9E-01 -0.0372 6.3E-01 -0.0147 4.8E-01 0.0367 5.8E-01 0.0685 1.2E-01 Roseburia_hominis UniRef90_G2SWZ6 Cluster: Anaerobic cobalt chelatase cbiK 0.15 0.0910 3.7E-02 2.9E-01 -0.1320 1.8E-01 -0.0139 5.9E-01 0.0718 3.8E-01 0.0962 8.3E-02 Roseburia_hominis UniRef90_R9KR53 Cluster: 30S ribosomal protein S10 0.22 0.1255 3.7E-02 2.9E-01 -0.0124 9.2E-01 -0.0019 9.6E-01 0.0910 4.1E-01 0.2332 1.8E-03 Roseburia_hominis UniRef90_G2T602 Cluster: ATP synthase epsilon chain 0.13 0.1173 3.8E-02 2.9E-01 -0.1120 3.8E-01 -0.0101 7.6E-01 0.0238 8.2E-01 0.0817 2.6E-01 Roseburia_hominis UniRef90_G2T3E7 Cluster: Chemotaxis protein CheY 0.13 0.1283 3.8E-02 2.9E-01 -0.0359 8.0E-01 0.0138 7.0E-01 0.1742 1.4E-01 0.0565 4.7E-01 Roseburia_hominis UniRef90_G2T1Z4 Cluster: Trigger factor 0.21 0.1499 3.9E-02 2.9E-01 -0.1357 4.0E-01 -0.0140 7.4E-01 0.0443 7.4E-01 0.1264 1.6E-01 Roseburia_hominis UniRef90_G2T0P6 Cluster: Dipeptide ABC transporter ATP-binding protein 0.14 0.0892 3.9E-02 2.9E-01 -0.0383 6.9E-01 -0.0249 3.3E-01 0.0687 3.9E-01 0.0077 8.9E-01 Roseburia_hominis UniRef90_G2T1T9 Cluster: Proline--tRNA ligase 0.13 0.0648 4.0E-02 2.9E-01 -0.0726 3.0E-01 -0.0297 1.1E-01 -0.1010 8.4E-02 -0.0100 8.0E-01 Roseburia_hominis UniRef90_G2SXA3 Cluster: Electron transfer flavoprotein subunit alpha 0.10 0.0969 4.0E-02 2.9E-01 0.0139 9.0E-01 -0.0138 6.2E-01 0.0008 9.9E-01 0.0034 9.5E-01 56

Supplementary Data 3b UniRef90 Family Plasma TMAO Red meat Red meat Choline Choline Species Cluster Name Detection member ID Rate Effect P FDR Effect P Effect P Effect P Effect P Roseburia_hominis UniRef90_G2T088 Cluster: 2-dehydro-3-deoxyphosphogluconate aldolase/4-hydroxy-2- 0.15 0.0960 4.0E-02 2.9E-01 -0.1253 2.3E-01 -0.0231 4.1E-01 0.0693 4.3E-01 0.1291 3.2E-02 oxoglutarate aldolase Roseburia_hominis UniRef90_G2T083 Cluster: Glycoside hydrolase family 3 protein 0.10 0.0614 4.0E-02 2.8E-01 -0.0081 9.0E-01 -0.0339 5.0E-02 -0.0582 3.1E-01 -0.0265 4.8E-01 Roseburia_hominis UniRef90_G2T4D4 Cluster: ADP-glucose pyrophosphorylase 0.19 0.1199 4.1E-02 2.9E-01 -0.2250 8.0E-02 -0.0541 1.1E-01 -0.0289 7.9E-01 -0.0044 9.5E-01 Roseburia_hominis UniRef90_G2SXI2 Cluster: Methyl-accepting chemotaxis protein 0.16 0.0908 4.1E-02 2.9E-01 -0.1206 2.2E-01 -0.0299 2.6E-01 0.0192 8.2E-01 -0.0560 3.3E-01 Roseburia_hominis UniRef90_R5I3I9 Cluster: 5-dehydro-2-deoxygluconokinase 0.13 0.0864 4.2E-02 2.9E-01 -0.0666 4.8E-01 -0.0072 7.7E-01 0.1389 8.1E-02 0.0747 1.7E-01 Roseburia_hominis UniRef90_G2T1K3 Cluster: DNA translocase FtsK 0.13 0.0590 4.2E-02 2.9E-01 -0.0196 7.6E-01 0.0028 8.7E-01 0.0030 9.6E-01 0.0547 1.4E-01 Roseburia_hominis UniRef90_G2SZF2 Cluster: Chromosomal replication initiator protein DnaA 0.11 0.0786 4.3E-02 2.9E-01 -0.0572 5.1E-01 -0.0199 3.8E-01 -0.0168 8.2E-01 0.0512 2.9E-01 Roseburia_hominis UniRef90_R5HY37 Cluster: sn-glycerol-3-phosphate ABC transporter ATP-binding protein UgpC 0.26 0.1624 4.3E-02 2.9E-01 -0.1927 2.8E-01 -0.0313 5.0E-01 0.0348 8.2E-01 0.1389 1.6E-01 Roseburia_hominis UniRef90_D4K6N3 Cluster: TnpX site-specific recombinase 0.16 0.0362 4.5E-02 3.0E-01 -0.0068 8.7E-01 -0.0203 6.3E-02 0.0056 8.7E-01 -0.0060 8.0E-01 Roseburia_hominis UniRef90_D4JAL3 Cluster: Probable transaldolase 0.14 0.0885 4.6E-02 3.0E-01 -0.1132 2.4E-01 -0.0041 8.7E-01 -0.1130 1.5E-01 0.0162 7.7E-01 Roseburia_hominis UniRef90_G2T3J5 Cluster: DegV protein 0.16 0.0884 4.6E-02 3.0E-01 -0.1700 8.7E-02 -0.0411 1.2E-01 0.0104 9.0E-01 0.0401 4.8E-01 Roseburia_hominis UniRef90_G2SX67 Cluster: Ferredoxin hydrogenase 0.12 0.0705 4.7E-02 3.0E-01 -0.1195 1.2E-01 -0.0081 7.0E-01 -0.1154 8.0E-02 0.0781 8.5E-02 Roseburia_hominis UniRef90_G2T242 Cluster: HD-GYP domain-containing protein 0.10 0.0470 4.8E-02 3.1E-01 -0.0547 3.3E-01 -0.0151 3.1E-01 -0.0053 9.1E-01 0.0254 4.3E-01 Roseburia_hominis UniRef90_G2SWU4 Cluster: 50S ribosomal protein L21 0.14 0.1140 4.9E-02 3.1E-01 -0.2091 1.2E-01 -0.0252 4.6E-01 0.0940 3.9E-01 0.1321 7.4E-02 Roseburia_hominis UniRef90_R9KQU7 Cluster: 30S ribosomal protein S13 0.21 0.1383 4.9E-02 3.1E-01 -0.1215 4.3E-01 0.0068 8.7E-01 0.0995 4.4E-01 0.0506 5.8E-01 Roseburia_hominis UniRef90_G2T3E4 Cluster: Flagellar protein FliL 0.13 0.1168 5.1E-02 3.2E-01 -0.3152 1.8E-02 -0.0192 5.8E-01 0.0474 6.7E-01 0.1057 1.6E-01 Roseburia_hominis UniRef90_G2SZE8 Cluster: Glycerol kinase 0.23 0.1965 5.2E-02 3.2E-01 -0.0011 1.0E+00 -0.0178 7.6E-01 0.1933 3.0E-01 0.1530 2.3E-01 Roseburia_hominis UniRef90_G2SZ74 Cluster: FliD_C domain-containing protein 0.13 0.0732 5.3E-02 3.2E-01 -0.1387 1.0E-01 -0.0518 2.0E-02 0.0206 7.7E-01 -0.0336 4.9E-01 Roseburia_hominis UniRef90_C4Z796 Cluster: Peroxide-responsive repressor perR 0.17 0.0312 5.3E-02 3.2E-01 0.0407 2.5E-01 0.0058 5.4E-01 -0.0165 5.8E-01 0.0107 6.0E-01 Roseburia_hominis UniRef90_G2T4H2 Cluster: Methyl-accepting chemotaxis sensory transducer with Cache sensor 0.15 0.0749 5.3E-02 3.2E-01 -0.0153 8.6E-01 -0.0171 4.5E-01 0.0826 2.5E-01 0.0511 2.9E-01 Roseburia_hominis UniRef90_R5HQR5 Cluster: 3-hydroxybutyryl-CoA dehydrogenase 0.23 0.1327 5.4E-02 3.3E-01 -0.0515 7.4E-01 -0.0202 6.1E-01 0.0338 7.9E-01 0.0735 4.0E-01 Roseburia_hominis UniRef90_G2T3M6 Cluster: ABC-type uncharacterized transport system, permease component 0.15 0.0876 5.5E-02 3.3E-01 -0.0221 8.3E-01 -0.0079 7.7E-01 0.0704 4.0E-01 0.0644 2.7E-01 Roseburia_hominis UniRef90_G2T1P2 Cluster: Threonine synthase 0.12 0.0707 5.5E-02 3.3E-01 -0.1495 6.8E-02 -0.0136 5.3E-01 0.0361 5.9E-01 0.0388 4.1E-01 Roseburia_hominis UniRef90_G2T2J7 Cluster: 3-carboxymuconate cyclase 0.14 0.0834 5.5E-02 3.3E-01 -0.1094 2.6E-01 -0.0150 5.5E-01 -0.0443 5.9E-01 0.0441 4.2E-01 Roseburia_hominis UniRef90_G2SZD8 Cluster: SseB domain-containing protein 0.14 0.0854 5.5E-02 3.3E-01 -0.2166 2.8E-02 -0.0135 6.0E-01 0.0097 9.1E-01 0.0686 2.2E-01 Roseburia_hominis UniRef90_G2T455 Cluster: Peptidase_M56 domain-containing protein 0.15 0.1096 5.6E-02 3.3E-01 -0.0752 5.5E-01 0.0015 9.7E-01 -0.0577 5.9E-01 0.0668 3.6E-01 Roseburia_hominis UniRef90_G2SXF6 Cluster: Efflux transporter, RND family, MFP subunit 0.13 0.0716 5.7E-02 3.3E-01 -0.1486 7.5E-02 -0.0351 1.2E-01 -0.0846 2.4E-01 -0.0176 7.2E-01 Roseburia_hominis UniRef90_G2T2W0 Cluster: Methyl-accepting chemotaxis protein (MCP) 0.14 0.0868 5.7E-02 3.3E-01 -0.0049 9.6E-01 -0.0294 2.7E-01 0.0223 8.0E-01 0.0284 6.2E-01 Roseburia_hominis UniRef90_G2T322 Cluster: Carboxyl transferase 0.17 0.1115 5.8E-02 3.3E-01 -0.0189 8.8E-01 -0.0143 6.8E-01 0.0439 6.9E-01 0.1598 3.2E-02 Roseburia_hominis UniRef90_G2T604 Cluster: ATP synthase gamma chain 0.21 0.1289 5.8E-02 3.3E-01 -0.1555 3.0E-01 -0.0518 1.9E-01 -0.0115 9.3E-01 0.1095 2.0E-01 Roseburia_hominis UniRef90_D4KKN6 Cluster: Serine hydroxymethyltransferase 0.11 0.0576 5.8E-02 3.3E-01 -0.1757 1.2E-02 0.0003 9.9E-01 0.0143 8.0E-01 0.0548 1.7E-01 Roseburia_hominis UniRef90_G2T1U3 Cluster: Phosphomannomutase 0.14 0.0653 5.8E-02 3.3E-01 -0.1038 1.7E-01 -0.0169 4.1E-01 -0.0186 7.6E-01 -0.0035 9.4E-01 Roseburia_hominis UniRef90_G2SWW3 Cluster: Cell division protein SepF 0.12 0.0916 6.0E-02 3.4E-01 -0.1204 2.6E-01 -0.0277 3.3E-01 0.0675 4.5E-01 -0.0033 9.6E-01 Roseburia_hominis UniRef90_G2T2T8 Cluster: LytTR family transcriptional regulator 0.12 0.1059 6.1E-02 3.3E-01 -0.2693 3.2E-02 -0.0577 7.8E-02 0.0396 7.1E-01 0.0115 8.7E-01 Roseburia_hominis UniRef90_G2T505 Cluster: PSP1 C-terminal domain-containing protein 0.13 0.0738 6.2E-02 3.4E-01 -0.1696 5.5E-02 -0.0182 4.2E-01 -0.0559 4.5E-01 0.0085 8.6E-01 Roseburia_hominis UniRef90_G2SZE4 Cluster: DUF1667 domain-containing protein 0.14 0.1438 6.2E-02 3.4E-01 0.0585 7.3E-01 0.0256 5.7E-01 0.1564 2.7E-01 0.0960 3.3E-01 Roseburia_hominis UniRef90_G2T309 Cluster: Ion-translocating oxidoreductase complex subunit C 0.11 0.0593 6.2E-02 3.4E-01 -0.0212 7.7E-01 -0.0067 7.3E-01 0.0235 6.9E-01 0.0433 2.9E-01 Roseburia_hominis UniRef90_G2SWS4 Cluster: Histidinol dehydrogenase 0.10 0.0609 6.3E-02 3.4E-01 -0.0337 6.4E-01 -0.0178 3.6E-01 0.0349 5.7E-01 0.0254 5.4E-01 Roseburia_hominis UniRef90_G2SZ87 Cluster: Sortase B family protein 0.12 0.0797 6.3E-02 3.4E-01 -0.2044 3.5E-02 -0.0309 2.2E-01 0.0026 9.7E-01 0.1061 4.9E-02 Roseburia_hominis UniRef90_G2T3F9 Cluster: Chemotaxis protein CheW 0.11 0.0893 6.4E-02 3.4E-01 -0.0038 9.7E-01 -0.0284 3.1E-01 -0.0630 4.9E-01 -0.1232 4.1E-02 Roseburia_hominis UniRef90_G2T3E0 Cluster: Flagellar protein 0.11 0.1045 6.4E-02 3.4E-01 0.0099 9.4E-01 0.0208 5.4E-01 -0.0027 9.8E-01 0.0900 2.2E-01 Roseburia_hominis UniRef90_G2SZE7 Cluster: MIP family channel protein 0.21 0.1838 6.4E-02 3.3E-01 -0.0208 9.2E-01 -0.0374 5.2E-01 0.0550 7.7E-01 0.0158 9.0E-01 Roseburia_hominis UniRef90_G2SYB5 Cluster: Cell filamentation protein fic, putative 0.15 0.0495 6.6E-02 3.4E-01 -0.0945 1.2E-01 -0.0147 3.8E-01 0.0020 9.7E-01 0.0497 1.7E-01 Roseburia_hominis UniRef90_G2T248 Cluster: LacI family transcriptional regulator 0.19 0.1206 6.6E-02 3.4E-01 -0.0969 5.1E-01 -0.0411 2.8E-01 0.1996 1.1E-01 0.0438 6.0E-01 Roseburia_hominis UniRef90_G2T623 Cluster: Ribonuclease P protein component 0.11 0.0931 6.6E-02 3.4E-01 -0.0437 7.0E-01 0.0013 9.7E-01 0.0518 5.9E-01 0.1521 2.0E-02 Roseburia_hominis UniRef90_G2T2F1 Cluster: Inosine-5'-monophosphate dehydrogenase 0.15 0.0809 6.7E-02 3.4E-01 -0.0945 3.3E-01 -0.0275 2.8E-01 0.0621 4.5E-01 0.0561 3.1E-01 Roseburia_hominis UniRef90_R7QWQ7 Cluster: Electron transfer flavoprotein beta-subunit 0.23 0.1502 6.7E-02 3.4E-01 -0.0972 5.9E-01 -0.0245 6.1E-01 0.1015 5.1E-01 0.0008 9.9E-01 Roseburia_hominis UniRef90_G2SXL8 Cluster: ABC transporter ATP-binding protein 0.13 0.0792 6.7E-02 3.4E-01 -0.1475 1.3E-01 -0.0231 3.6E-01 0.0224 7.9E-01 0.0597 2.7E-01 Roseburia_hominis UniRef90_G2T0D2 Cluster: Dihydroorotate dehydrogenase B (NAD(+)), electron transfer 0.10 0.0669 6.8E-02 3.4E-01 -0.0774 3.5E-01 -0.0424 4.5E-02 -0.0217 7.6E-01 0.0025 9.6E-01 Roseburia_hominis UniRef90_G2SXR5 Cluster:subunit DNA polymerase I 0.13 0.0516 7.0E-02 3.4E-01 -0.0619 3.3E-01 -0.0113 5.0E-01 -0.0362 5.0E-01 0.0632 8.0E-02 Roseburia_hominis UniRef90_G2SX92 Cluster: Major facilitator superfamily MFS_1 0.13 0.0893 7.1E-02 3.5E-01 -0.0905 4.2E-01 0.0015 9.6E-01 -0.0747 4.2E-01 0.0048 9.4E-01 Roseburia_hominis UniRef90_R5HHD3 Cluster: 50S ribosomal protein L17 0.19 0.1218 7.2E-02 3.5E-01 -0.1838 2.1E-01 -0.0136 7.3E-01 0.0661 6.0E-01 0.1091 2.0E-01 Roseburia_hominis UniRef90_G2SXQ9 Cluster: UPF0210 protein ROSEINA2194_00039 0.12 0.0656 7.2E-02 3.5E-01 -0.0656 4.2E-01 -0.0359 9.0E-02 -0.0320 6.3E-01 0.0099 8.3E-01 Roseburia_hominis UniRef90_G2T2S8 Cluster: GTPase 0.11 0.0571 7.4E-02 3.5E-01 -0.0568 4.2E-01 0.0065 7.3E-01 0.0764 1.9E-01 0.0480 2.3E-01 Roseburia_hominis UniRef90_G2T350 Cluster: Methyl-accepting chemotaxis sensory transducer 0.14 0.0651 7.5E-02 3.5E-01 -0.0646 4.2E-01 0.0013 9.5E-01 0.1268 6.6E-02 0.0057 9.0E-01 Roseburia_hominis UniRef90_G2T436 Cluster: Glycosyltransferase 0.11 0.0582 7.6E-02 3.5E-01 -0.0339 6.4E-01 -0.0160 4.1E-01 0.0296 6.3E-01 0.0320 4.5E-01 Roseburia_hominis UniRef90_C4Z761 Cluster: Citrate synthase 0.11 0.0060 7.6E-02 3.5E-01 -0.0045 5.7E-01 -0.0028 1.8E-01 -0.0038 5.7E-01 0.0057 2.0E-01 Roseburia_hominis UniRef90_R6SKW0 Cluster: 30S ribosomal protein S7 0.23 0.1188 7.6E-02 3.5E-01 -0.2442 9.8E-02 -0.0320 4.1E-01 0.0940 4.5E-01 0.1182 1.6E-01 Roseburia_hominis UniRef90_G2T1P1 Cluster: Chemotaxis protein CheX 0.15 0.0913 7.7E-02 3.6E-01 0.0617 5.9E-01 0.0318 2.9E-01 0.0871 3.6E-01 0.2218 5.3E-04 Roseburia_hominis UniRef90_R5I027 Cluster: FAD-binding FR-type domain-containing protein 0.13 0.0682 7.7E-02 3.6E-01 -0.1530 7.0E-02 -0.0440 5.3E-02 0.0739 2.9E-01 0.0441 3.6E-01 Roseburia_hominis UniRef90_G2SXD9 Cluster: Galactose-1-phosphate uridylyltransferase 0.13 0.0536 7.8E-02 3.6E-01 -0.0648 3.4E-01 -0.0050 7.8E-01 -0.0200 7.2E-01 -0.0085 8.3E-01 Roseburia_hominis UniRef90_G2T0P5 Cluster: ABC transporter ATP-binding protein 0.14 0.0688 7.8E-02 3.6E-01 0.0012 9.9E-01 -0.0398 8.0E-02 -0.0569 4.3E-01 -0.0199 6.8E-01 Roseburia_hominis UniRef90_G2SWP3 Cluster: Transketolase domain protein 0.14 0.0852 7.9E-02 3.6E-01 -0.0753 4.8E-01 -0.0144 6.1E-01 0.0202 8.2E-01 0.1401 2.1E-02 Roseburia_hominis UniRef90_R5I077 Cluster: Ribonuclease Y 0.21 0.1103 8.0E-02 3.6E-01 -0.0183 8.9E-01 -0.0472 2.0E-01 0.1178 3.1E-01 0.1327 9.4E-02 Roseburia_hominis UniRef90_D4LZR7 Cluster: HTH cro/C1-type domain-containing protein 0.18 0.0172 8.0E-02 3.6E-01 -0.0294 1.9E-01 -0.0101 8.3E-02 -0.0131 4.9E-01 0.0203 1.0E-01 Roseburia_hominis UniRef90_G2SYC9 Cluster: Methyl-accepting chemotaxis sensory transducer 0.16 0.0733 8.2E-02 3.7E-01 -0.1155 2.2E-01 -0.0391 1.2E-01 -0.0151 8.5E-01 0.0897 9.6E-02 Roseburia_hominis UniRef90_D4KPS8 Cluster: Argininosuccinate synthase 0.12 0.0621 8.2E-02 3.7E-01 -0.1624 3.9E-02 -0.0019 9.3E-01 -0.0738 2.7E-01 0.0343 4.4E-01 Roseburia_hominis UniRef90_G2SZE3 Cluster: HTH tetR-type domain-containing protein 0.10 0.0634 8.4E-02 3.7E-01 -0.0934 2.7E-01 0.0171 4.4E-01 0.0209 7.7E-01 0.0535 2.6E-01 Roseburia_hominis UniRef90_R5HI14 Cluster: Transcription termination/antitermination protein NusG 0.19 0.1239 8.5E-02 3.7E-01 -0.1455 3.6E-01 -0.0493 2.4E-01 0.0679 6.1E-01 0.1250 1.7E-01 Roseburia_hominis UniRef90_R7QZB0 Cluster: AA_TRNA_LIGASE_II domain-containing protein 0.15 0.0623 8.6E-02 3.7E-01 -0.0607 4.4E-01 -0.0288 1.7E-01 -0.0559 4.1E-01 0.0539 2.4E-01 Roseburia_hominis UniRef90_G2SYE3 Cluster: Flotillin 2 0.15 0.0689 8.6E-02 3.7E-01 -0.1043 2.4E-01 -0.0061 7.9E-01 0.0368 6.2E-01 -0.0243 6.3E-01 Roseburia_hominis UniRef90_D4KVH2 Cluster: Glutamine--tRNA ligase 0.16 0.0646 8.7E-02 3.7E-01 -0.0873 2.9E-01 0.0279 2.1E-01 0.0317 6.5E-01 0.0869 7.0E-02 Roseburia_hominis UniRef90_G2SWQ6 Cluster: Guanylate kinase 0.12 0.0740 8.8E-02 3.7E-01 -0.0280 7.7E-01 -0.0190 4.5E-01 -0.0150 8.5E-01 0.0285 6.0E-01 Roseburia_hominis UniRef90_R7BSZ3 Cluster: Phosphoenolpyruvate carboxykinase (ATP) 0.31 0.0816 8.9E-02 3.8E-01 -0.1183 2.7E-01 -0.0444 1.1E-01 -0.0187 8.4E-01 0.0868 1.5E-01 Roseburia_hominis UniRef90_G2SYR6 Cluster: Aldose 1-epimerase 0.11 0.0546 8.9E-02 3.8E-01 -0.0940 1.9E-01 -0.0326 8.3E-02 0.0628 3.0E-01 0.0506 2.2E-01 Roseburia_hominis UniRef90_G2SXA4 Cluster: Electron transfer flavoprotein subunit alpha/FixB family protein 0.12 0.0776 9.0E-02 3.8E-01 -0.1131 2.7E-01 -0.0153 5.7E-01 0.1151 1.8E-01 -0.0124 8.3E-01 Roseburia_hominis UniRef90_D4KMZ5 Cluster: 50S ribosomal protein L32 0.12 0.0882 9.1E-02 3.8E-01 -0.1711 1.3E-01 -0.0131 6.7E-01 0.0949 3.3E-01 0.1193 7.3E-02 Roseburia_hominis UniRef90_D4KYQ2 Cluster: Glucose-6-phosphate isomerase 0.15 0.0660 9.2E-02 3.8E-01 -0.1942 2.6E-02 -0.0139 5.6E-01 -0.0086 9.1E-01 0.0053 9.2E-01 Roseburia_hominis UniRef90_D4KPH2 Cluster: Ribosome hibernation promoting factor 0.19 0.1110 9.3E-02 3.8E-01 -0.1065 4.7E-01 -0.0471 2.3E-01 0.1066 3.9E-01 0.0674 4.2E-01 Roseburia_hominis UniRef90_R5HI46 Cluster: GTPase Der 0.11 0.0526 9.4E-02 3.8E-01 -0.0731 3.0E-01 -0.0303 1.0E-01 -0.0391 5.1E-01 -0.0340 3.9E-01 Roseburia_hominis UniRef90_G2SXV7 Cluster: DAK2 domain/DegV family protein 0.12 0.0728 9.5E-02 3.9E-01 -0.2403 1.1E-02 -0.0396 1.2E-01 -0.0583 4.7E-01 0.0797 1.4E-01 Roseburia_hominis UniRef90_G2T5X2 Cluster: TPR_REGION domain-containing protein 0.13 0.0407 9.5E-02 3.9E-01 0.0037 9.5E-01 -0.0208 1.5E-01 -0.0285 5.3E-01 0.0083 7.9E-01 Roseburia_hominis UniRef90_C4ZGI2 Cluster: 3-hydroxybutyryl-coA dehydratase 0.22 0.1118 9.8E-02 3.9E-01 -0.0793 6.0E-01 -0.0287 4.7E-01 0.0559 6.6E-01 0.1219 1.5E-01 Roseburia_hominis UniRef90_G2SXN4 Cluster: Signal recognition particle protein 0.16 0.0763 1.0E-01 4.0E-01 -0.2064 4.7E-02 -0.0425 1.1E-01 0.0443 6.0E-01 0.1322 2.4E-02 Roseburia_hominis UniRef90_G2SX93 Cluster: Na+/solute symporter 0.16 0.0885 1.0E-01 4.0E-01 -0.0214 8.7E-01 0.0173 5.8E-01 -0.0079 9.4E-01 0.0835 2.2E-01 Roseburia_hominis UniRef90_G2SZZ6 Cluster: Cell division protein FtsX 0.11 0.0519 1.0E-01 4.0E-01 -0.0610 3.9E-01 -0.0235 2.1E-01 -0.0038 9.5E-01 -0.0194 6.3E-01 Roseburia_hominis UniRef90_G2T251 Cluster: Inner membrane ABC transporter permease protein yjfF 0.13 0.0714 1.0E-01 4.0E-01 -0.1633 1.0E-01 -0.0398 1.3E-01 -0.0493 5.4E-01 -0.0308 5.8E-01 Roseburia_hominis UniRef90_G2SX99 Cluster: Enoyl-CoA hydratase 0.10 0.0703 1.1E-01 4.1E-01 0.0218 8.2E-01 0.0125 6.2E-01 0.0773 3.4E-01 0.0993 6.9E-02 Roseburia_hominis UniRef90_G2SXI8 Cluster: PIN7 domain-containing protein 0.15 0.0690 1.1E-01 4.0E-01 -0.1158 2.2E-01 -0.0068 7.9E-01 0.0701 3.8E-01 0.0802 1.3E-01 Roseburia_hominis UniRef90_G2T1D5 Cluster: Acetolactate synthase 0.10 0.0423 1.1E-01 4.0E-01 -0.0328 5.8E-01 0.0018 9.1E-01 0.0465 3.5E-01 0.0948 5.6E-03 Roseburia_hominis UniRef90_G2SXN7 Cluster: MFS transporter xanthine/uracil permease 0.13 0.0616 1.1E-01 4.0E-01 0.0756 3.8E-01 -0.0199 3.7E-01 0.0691 3.4E-01 0.0498 2.9E-01 Roseburia_hominis UniRef90_G2SWZ0 Cluster: Phosphopentomutase 0.11 0.0565 1.1E-01 4.0E-01 -0.0211 7.9E-01 -0.0221 2.9E-01 0.0203 7.6E-01 0.0549 2.2E-01 Roseburia_hominis UniRef90_G2T0B3 Cluster: Glutamine--fructose-6-phosphate aminotransferase [isomerizing] 0.13 0.0548 1.1E-01 4.1E-01 0.0050 9.5E-01 -0.0040 8.4E-01 -0.0073 9.1E-01 0.0424 3.2E-01 57

Supplementary Data 3b UniRef90 Family Plasma TMAO Red meat Red meat Choline Choline Species Cluster Name Detection member ID Rate Effect P FDR Effect P Effect P Effect P Effect P Roseburia_hominis UniRef90_G2T207 Cluster: Two-component system, PleD related family, response regulator 0.15 0.0672 1.1E-01 4.0E-01 -0.0468 6.2E-01 -0.0153 5.3E-01 -0.0664 4.0E-01 0.0371 4.8E-01 Roseburia_hominis UniRef90_G2T3H5 Cluster: Polysaccharide deacetylase Est4C 0.13 0.0720 1.1E-01 4.0E-01 -0.0959 3.4E-01 -0.0362 1.7E-01 0.0617 4.7E-01 0.0433 4.4E-01 Roseburia_hominis UniRef90_C4ZBS5 Cluster: 30S ribosomal protein S3 0.25 0.1172 1.1E-01 4.0E-01 -0.1573 3.4E-01 -0.0606 1.6E-01 -0.0155 9.1E-01 0.1253 1.8E-01 Roseburia_hominis UniRef90_G2SXK6 Cluster: Chemotaxis protein CheV 0.19 0.0901 1.1E-01 4.0E-01 -0.1277 3.2E-01 -0.0419 2.1E-01 0.0157 8.8E-01 0.0377 6.0E-01 Roseburia_hominis UniRef90_G2T3H6 Cluster: Polymer-forming cytoskeletal protein 0.11 0.0629 1.2E-01 4.0E-01 -0.0781 3.7E-01 -0.0447 5.8E-02 -0.0198 7.9E-01 -0.0081 8.7E-01 Roseburia_hominis UniRef90_G2T0A5 Cluster: Beta-methylgalactoside transporter inner membrane component 0.17 0.0828 1.2E-01 4.1E-01 -0.0818 4.8E-01 -0.0132 6.7E-01 -0.0760 4.4E-01 0.0440 5.0E-01 Roseburia_hominis UniRef90_G2T0A4 Cluster: Galactose/methyl galactoside import ATP-binding protein MglA 0.16 0.0758 1.2E-01 4.1E-01 -0.0518 6.2E-01 -0.0323 2.5E-01 -0.0055 9.5E-01 0.0475 4.3E-01 Roseburia_hominis UniRef90_G2T607 Cluster: ATP synthase subunit b 0.17 0.1071 1.2E-01 4.1E-01 0.0293 8.5E-01 0.0263 5.1E-01 0.1337 3.0E-01 0.1534 7.8E-02 Roseburia_hominis UniRef90_G2T1U0 Cluster: CCA tRNA nucleotidyltransferase 0.11 0.0524 1.2E-01 4.1E-01 -0.0377 6.2E-01 -0.0409 3.9E-02 0.0116 8.5E-01 0.0494 2.5E-01 Roseburia_hominis UniRef90_G2T029 Cluster: Phosphohydrolase 0.13 0.0593 1.2E-01 4.1E-01 -0.0095 9.1E-01 0.0227 3.2E-01 -0.0094 9.0E-01 0.0231 6.4E-01 Roseburia_hominis UniRef90_G2T2U1 Cluster: Methyl-accepting chemotaxis sensory transducer 0.14 0.0602 1.2E-01 4.1E-01 -0.0668 4.4E-01 -0.0029 9.0E-01 0.0484 5.0E-01 0.0676 1.7E-01 Roseburia_hominis UniRef90_G2T1N6 Cluster: Citrate synthase 0.11 0.0591 1.2E-01 4.1E-01 -0.1248 1.4E-01 -0.0364 9.9E-02 -0.0534 4.5E-01 0.0339 4.8E-01 Roseburia_hominis UniRef90_G2T1P3 Cluster: Methyl-accepting chemotaxis sensory transducer 0.15 0.0628 1.2E-01 4.1E-01 -0.0561 5.5E-01 -0.0177 4.7E-01 -0.0133 8.6E-01 0.0643 2.2E-01 Roseburia_hominis UniRef90_G2T4Z2 Cluster: 30S ribosomal protein S18 0.18 0.0834 1.2E-01 4.1E-01 0.0886 4.6E-01 -0.0062 8.4E-01 -0.0247 8.0E-01 0.0838 2.2E-01 Roseburia_hominis UniRef90_G2T4D5 Cluster: Glucose-1-phosphate adenylyltransferase 0.22 0.0924 1.2E-01 4.1E-01 -0.1191 3.7E-01 -0.0434 2.1E-01 0.0854 4.4E-01 0.0439 5.6E-01 Roseburia_hominis UniRef90_G2T5N3 Cluster: 50S ribosomal protein L3 0.24 0.0965 1.2E-01 4.1E-01 -0.1150 4.0E-01 -0.0428 2.4E-01 -0.1096 3.5E-01 0.0661 4.0E-01 Roseburia_hominis UniRef90_G2T0Z5 Cluster: CarD family transcriptional regulator 0.13 0.0810 1.2E-01 4.1E-01 -0.1632 1.7E-01 -0.0125 6.8E-01 -0.0523 6.0E-01 -0.0829 2.1E-01 Roseburia_hominis UniRef90_G2T3M5 Cluster: Deoxyribose-phosphate aldolase 0.11 0.0568 1.3E-01 4.1E-01 -0.1537 5.8E-02 -0.0432 4.9E-02 0.0205 7.7E-01 0.0547 2.5E-01 Roseburia_hominis UniRef90_D4LY41 Cluster: Signal transduction histidine-protein kinase BaeS 0.12 -0.0050 1.3E-01 4.1E-01 0.0136 6.5E-02 0.0020 3.0E-01 -0.0039 5.3E-01 0.0045 3.0E-01 Roseburia_hominis UniRef90_G2T186 Cluster: Capsule synthesis protein, CapA 0.12 0.0492 1.3E-01 4.2E-01 -0.1062 1.4E-01 -0.0032 8.6E-01 0.0024 9.7E-01 0.0286 4.8E-01 Roseburia_hominis UniRef90_G2T5L0 Cluster: Methionine aminopeptidase 0.12 0.0607 1.3E-01 4.2E-01 -0.1060 2.3E-01 -0.0391 9.8E-02 -0.0653 3.8E-01 0.0038 9.4E-01 Roseburia_hominis UniRef90_G2T321 Cluster: Sodium pump decarboxylase 0.17 0.0900 1.3E-01 4.2E-01 -0.1271 3.4E-01 -0.0295 4.0E-01 0.0398 7.2E-01 0.0450 5.5E-01 Roseburia_hominis UniRef90_G2T5L5 Cluster: 30S ribosomal protein S5 0.21 0.1087 1.3E-01 4.2E-01 -0.1814 2.6E-01 -0.0468 2.7E-01 0.1460 2.8E-01 0.1830 4.3E-02 Roseburia_hominis UniRef90_G2SY01 Cluster: Aspartate--tRNA ligase 0.15 0.0503 1.3E-01 4.2E-01 -0.0790 2.9E-01 -0.0303 1.2E-01 -0.0331 5.9E-01 0.0247 5.6E-01 Roseburia_hominis UniRef90_D4L1Y4 Cluster: HTH cro/C1-type domain-containing protein 0.24 0.0307 1.3E-01 4.2E-01 -0.0618 1.8E-01 -0.0052 6.7E-01 -0.0280 4.3E-01 0.0381 1.4E-01 Roseburia_hominis UniRef90_G2T311 Cluster: Protein-glutamate O-methyltransferase CheR 0.14 0.0761 1.3E-01 4.2E-01 -0.1302 2.5E-01 -0.0397 1.7E-01 0.0359 7.1E-01 0.0323 6.1E-01 Roseburia_hominis UniRef90_G2T5A0 Cluster: YbbR family protein 0.11 0.0446 1.3E-01 4.2E-01 -0.0964 1.5E-01 -0.0229 2.0E-01 0.0269 6.3E-01 0.0437 2.6E-01 Roseburia_hominis UniRef90_G2T1X5 Cluster: UDP-N-acetylenolpyruvoylglucosamine reductase 0.11 0.0544 1.4E-01 4.3E-01 -0.0376 6.4E-01 -0.0182 3.9E-01 0.0398 5.6E-01 0.0460 3.2E-01 Roseburia_hominis UniRef90_G2T5L1 Cluster: Adenylate kinase 0.12 0.0664 1.4E-01 4.3E-01 -0.0237 8.1E-01 0.0028 9.2E-01 0.0376 6.5E-01 0.0180 7.5E-01 Roseburia_hominis UniRef90_G2T1T2 Cluster: HD-GYP domain-containing protein 0.13 0.0570 1.4E-01 4.3E-01 -0.0700 4.1E-01 -0.0135 5.5E-01 0.0278 6.9E-01 0.0815 9.2E-02 Roseburia_hominis UniRef90_C4Z791 Cluster: Hemerythrin 0.14 0.0365 1.4E-01 4.3E-01 -0.0367 5.1E-01 0.0147 3.3E-01 -0.0003 9.9E-01 0.0294 3.6E-01 Roseburia_hominis UniRef90_G2T4C3 Cluster: Hydrolase 0.11 0.0440 1.4E-01 4.3E-01 -0.1063 1.0E-01 -0.0308 8.1E-02 0.0097 8.6E-01 -0.0045 9.1E-01 Roseburia_hominis UniRef90_G2T0S9 Cluster: Alpha-N-arabinofuranosidase 0.12 0.0481 1.4E-01 4.3E-01 -0.0523 4.8E-01 -0.0177 3.8E-01 -0.0093 8.8E-01 0.0317 4.6E-01 Roseburia_hominis UniRef90_G2T297 Cluster: Cysteine desulfurase IscS 0.11 0.0404 1.4E-01 4.3E-01 -0.1003 9.3E-02 -0.0213 1.9E-01 -0.0380 4.5E-01 -0.0016 9.6E-01 Roseburia_hominis UniRef90_G2SX58 Cluster: DAK2 domain/DegV family protein 0.12 0.0545 1.4E-01 4.3E-01 -0.1695 3.6E-02 -0.0383 8.1E-02 -0.0022 9.7E-01 0.0882 6.3E-02 Roseburia_hominis UniRef90_G2SWR3 Cluster: ATPase 0.13 0.0677 1.4E-01 4.3E-01 -0.0503 6.2E-01 0.0149 5.8E-01 0.0648 4.5E-01 -0.0090 8.8E-01 Roseburia_hominis UniRef90_G2T3D5 Cluster: Flagellar protein export ATPase FliI 0.17 0.0759 1.4E-01 4.3E-01 -0.2312 4.4E-02 -0.0173 5.7E-01 -0.0244 8.0E-01 0.0673 3.1E-01 Roseburia_hominis UniRef90_G2T3G0 Cluster: Chemotaxis protein CheC 0.12 0.0603 1.4E-01 4.3E-01 0.0527 5.7E-01 0.0321 1.9E-01 0.0552 4.8E-01 0.0820 1.2E-01 Roseburia_hominis UniRef90_G2T187 Cluster: 2,3-bisphosphoglycerate-independent phosphoglycerate mutase 0.15 0.0589 1.5E-01 4.3E-01 -0.1187 1.8E-01 0.0079 7.4E-01 0.0176 8.1E-01 0.0742 1.5E-01 Roseburia_hominis UniRef90_C4ZB99 Cluster: Elongation factor Tu 0.33 0.1111 1.5E-01 4.4E-01 -0.2096 2.3E-01 -0.0578 1.9E-01 -0.0707 6.3E-01 0.0973 3.1E-01 Roseburia_hominis UniRef90_G2T1K6 Cluster: Glycogen synthase 0.13 0.0498 1.5E-01 4.4E-01 0.0803 2.9E-01 0.0087 6.7E-01 0.0163 8.0E-01 0.0400 3.6E-01 Roseburia_hominis UniRef90_G2T3G8 Cluster: Elongation factor Ts 0.19 0.0876 1.5E-01 4.4E-01 -0.1565 2.4E-01 -0.0184 6.0E-01 0.1790 1.1E-01 0.1517 4.7E-02 Roseburia_hominis UniRef90_G2SXF3 Cluster: EAL domain-containing protein 0.11 0.0387 1.5E-01 4.4E-01 -0.0004 9.9E-01 0.0055 7.3E-01 0.0107 8.3E-01 0.0491 1.6E-01 Roseburia_hominis UniRef90_G2T184 Cluster: Phosphoglycerate kinase 0.21 0.0894 1.5E-01 4.4E-01 -0.0075 9.6E-01 -0.0615 8.9E-02 0.0486 6.8E-01 0.1131 1.4E-01 Roseburia_hominis UniRef90_R5HSD3 Cluster: Glycine--tRNA ligase 0.19 0.0495 1.5E-01 4.4E-01 -0.0937 2.2E-01 -0.0283 1.6E-01 -0.0729 2.6E-01 0.0764 7.9E-02 Roseburia_hominis UniRef90_G2T2H7 Cluster: Soluble lytic murein transglycosylase 0.10 0.0566 1.6E-01 4.4E-01 -0.0232 8.0E-01 -0.0208 3.9E-01 0.0748 3.3E-01 0.0068 9.0E-01 Roseburia_hominis UniRef90_R6BS42 Cluster: Beta sliding clamp 0.11 0.0510 1.6E-01 4.4E-01 -0.0055 9.5E-01 0.0125 5.5E-01 0.0460 4.9E-01 0.0699 1.2E-01 Roseburia_hominis UniRef90_G2SWV2 Cluster: LexA repressor 0.10 0.0637 1.6E-01 4.4E-01 -0.0687 4.9E-01 0.0096 7.2E-01 0.0331 6.9E-01 0.0632 2.7E-01 Roseburia_hominis UniRef90_C4Z954 Cluster: Glyceraldehyde-3-phosphate dehydrogenase 0.31 0.1024 1.6E-01 4.4E-01 -0.0285 8.6E-01 -0.0335 4.3E-01 -0.0334 8.1E-01 0.1299 1.5E-01 Roseburia_hominis UniRef90_G2T620 Cluster: Protein jag 0.12 0.0609 1.6E-01 4.4E-01 -0.1273 1.9E-01 -0.0005 9.8E-01 -0.0200 8.0E-01 -0.0133 8.1E-01 Roseburia_hominis UniRef90_G2T415 Cluster: Peptidylprolyl isomerase 0.12 0.0493 1.6E-01 4.4E-01 -0.1607 4.1E-02 -0.0142 4.8E-01 -0.0737 2.6E-01 0.0599 1.7E-01 Roseburia_hominis UniRef90_G2T1J9 Cluster: Xanthine phosphoribosyltransferase 0.11 0.0517 1.6E-01 4.4E-01 -0.1106 1.8E-01 -0.0175 4.3E-01 0.0548 4.3E-01 0.0906 5.5E-02 Roseburia_hominis UniRef90_G2T092 Cluster: ATP-dependent protease ATP-binding subunit ClpX 0.10 0.0373 1.6E-01 4.5E-01 -0.0874 1.7E-01 -0.0003 9.8E-01 -0.0124 8.2E-01 0.0626 8.7E-02 Roseburia_hominis UniRef90_G2T4Z4 Cluster: 30S ribosomal protein S6 0.19 0.0827 1.6E-01 4.5E-01 0.0080 9.5E-01 0.0024 9.4E-01 0.0952 3.9E-01 0.1685 2.3E-02 Roseburia_hominis UniRef90_G2T0P8 Cluster: Extracellular ligand-binding receptor 0.11 0.0439 1.6E-01 4.5E-01 -0.1049 1.4E-01 -0.0149 4.2E-01 0.0843 1.4E-01 0.0824 3.9E-02 Roseburia_hominis UniRef90_G2T606 Cluster: ATP synthase subunit delta 0.15 0.0945 1.6E-01 4.5E-01 -0.1352 3.7E-01 -0.0576 1.5E-01 0.0193 8.8E-01 0.1352 1.1E-01 Roseburia_hominis UniRef90_G2T597 Cluster: dTDP-4-dehydrorhamnose reductase 0.10 0.0455 1.7E-01 4.5E-01 -0.0885 2.1E-01 -0.0082 6.7E-01 -0.0520 3.9E-01 0.0523 2.1E-01 Roseburia_hominis UniRef90_R5HLG0 Cluster: IMP_cyclohyd domain-containing protein 0.13 0.0505 1.7E-01 4.5E-01 -0.1116 1.7E-01 0.0016 9.4E-01 0.0183 7.9E-01 0.0817 7.9E-02 Roseburia_hominis UniRef90_R5HWT6 Cluster: 50S ribosomal protein L23 0.18 0.1131 1.7E-01 4.5E-01 -0.1880 3.1E-01 -0.0799 9.3E-02 0.1566 3.1E-01 0.0320 7.6E-01 Roseburia_hominis UniRef90_G2T3Q6 Cluster: Stage 0 sporulation protein A homolog 0.12 0.0556 1.7E-01 4.5E-01 -0.1185 1.8E-01 0.0036 8.8E-01 0.0225 7.7E-01 0.0473 3.6E-01 Roseburia_hominis UniRef90_G2T305 Cluster: Ion-translocating oxidoreductase complex subunit A 0.13 0.0634 1.7E-01 4.5E-01 -0.0724 4.7E-01 -0.0241 3.7E-01 -0.0716 4.0E-01 0.0465 4.3E-01 Roseburia_hominis UniRef90_G2SX19 Cluster: Arginine--tRNA ligase 0.11 0.0321 1.7E-01 4.5E-01 -0.0400 4.5E-01 -0.0092 5.1E-01 -0.0020 9.7E-01 0.0088 7.7E-01 Roseburia_hominis UniRef90_G2T1R5 Cluster: Signaling protein 0.12 0.0562 1.7E-01 4.5E-01 -0.1315 1.5E-01 -0.0424 7.7E-02 0.0992 2.0E-01 0.0188 7.2E-01 Roseburia_hominis UniRef90_G2T1D7 Cluster: ACT domain-containing protein 0.11 0.0541 1.7E-01 4.5E-01 -0.2378 6.0E-03 -0.0031 8.9E-01 -0.0618 4.0E-01 0.0224 6.5E-01 Roseburia_hominis UniRef90_G2SZI6 Cluster: ATP-dependent RNA helicase 0.14 0.0444 1.7E-01 4.5E-01 -0.0930 1.9E-01 -0.0283 1.4E-01 -0.0020 9.7E-01 0.0269 5.2E-01 Roseburia_hominis UniRef90_G2SXF4 Cluster: ABC-type transport system, involved in lipoprotein release, 0.12 0.0528 1.7E-01 4.5E-01 -0.1006 2.5E-01 -0.0317 1.7E-01 -0.0260 7.3E-01 0.0830 9.6E-02 permease component Roseburia_hominis UniRef90_G2SXA6 Cluster: Aminotransferase class I/II-fold pyridoxal phosphate-dependent 0.10 0.0498 1.8E-01 4.5E-01 0.0189 8.2E-01 -0.0041 8.5E-01 -0.0669 3.3E-01 0.0194 6.8E-01 enzyme Roseburia_hominis UniRef90_G2SXS2 Cluster: Stk1 family PASTA domain-containing Ser/Thr kinase 0.12 0.0383 1.8E-01 4.5E-01 -0.0158 8.0E-01 0.0000 1.0E+00 0.0370 4.8E-01 0.0490 1.8E-01 Roseburia_hominis UniRef90_G2SYH7 Cluster: NagC/XylR family transcriptional regulator 0.11 0.0422 1.8E-01 4.6E-01 -0.0107 8.8E-01 -0.0092 6.2E-01 -0.0013 9.8E-01 0.0283 4.8E-01 Roseburia_hominis UniRef90_D4L2U4 Cluster: S-adenosylmethionine synthase 0.13 0.0482 1.8E-01 4.6E-01 -0.0925 2.4E-01 -0.0082 7.0E-01 -0.0229 7.3E-01 0.0820 7.3E-02 Roseburia_hominis UniRef90_R5W278 Cluster: NifU_N domain-containing protein 0.23 0.0849 1.8E-01 4.6E-01 -0.1871 1.8E-01 -0.0346 3.5E-01 -0.0906 4.4E-01 0.1415 7.5E-02 Roseburia_hominis UniRef90_G2SWW8 Cluster: Serine-type D-Ala-D-Ala carboxypeptidase 0.11 0.0462 1.8E-01 4.6E-01 -0.1451 5.4E-02 -0.0058 7.8E-01 -0.0531 4.1E-01 0.0666 1.3E-01 Roseburia_hominis UniRef90_G2SX95 Cluster: Acyl-CoA dehydrogenase 0.13 0.0586 1.8E-01 4.6E-01 0.0359 7.1E-01 0.0153 5.5E-01 0.0470 5.6E-01 0.0680 2.2E-01 Roseburia_hominis UniRef90_G2T0N9 Cluster: SBP_bac_5 domain-containing protein 0.20 0.0834 1.8E-01 4.6E-01 -0.1227 3.7E-01 -0.0424 2.5E-01 0.0760 5.1E-01 0.0913 2.5E-01 Roseburia_hominis UniRef90_C4ZBF9 Cluster: UDP-glucose 4-epimerase 0.12 0.0442 1.8E-01 4.5E-01 -0.0919 2.2E-01 -0.0312 1.0E-01 -0.0483 4.4E-01 -0.0038 9.3E-01 Roseburia_hominis UniRef90_D4KXM1 Cluster: Isocitrate dehydrogenase [NADP] 0.12 0.0419 1.8E-01 4.6E-01 -0.0578 4.0E-01 -0.0073 6.9E-01 0.0355 5.4E-01 0.0499 2.1E-01 Roseburia_hominis UniRef90_G2T2J6 Cluster: Peptidase U32 0.11 0.0402 1.8E-01 4.6E-01 -0.0195 7.7E-01 -0.0137 4.5E-01 -0.0219 7.0E-01 0.0503 2.0E-01 Roseburia_hominis UniRef90_G2T0C0 Cluster: Adenine deaminase 0.13 0.0439 1.8E-01 4.6E-01 0.0262 7.2E-01 -0.0160 4.1E-01 0.0633 3.1E-01 0.0490 2.4E-01 Roseburia_hominis UniRef90_G2T399 Cluster: Murein transglycosylase 0.18 0.0469 1.9E-01 4.6E-01 0.0593 4.6E-01 0.0104 6.2E-01 0.0236 7.3E-01 0.1066 1.6E-02 Roseburia_hominis UniRef90_G2T3F4 Cluster: Flagellar biosynthesis protein FlhF 0.11 0.0438 1.9E-01 4.6E-01 0.0450 5.5E-01 0.0171 3.9E-01 0.0002 1.0E+00 0.0946 2.7E-02 Roseburia_hominis UniRef90_G2SZJ7 Cluster: Flagellar hook-associated protein FlgK 0.18 0.0622 1.9E-01 4.6E-01 -0.1425 1.7E-01 -0.0270 3.3E-01 -0.0086 9.2E-01 -0.0310 6.0E-01 Roseburia_hominis UniRef90_R5HJF6 Cluster: Phosphoglucomutase 0.14 0.0363 1.9E-01 4.6E-01 0.0422 4.9E-01 -0.0084 6.1E-01 -0.0010 9.8E-01 0.0572 9.9E-02 Roseburia_hominis UniRef90_R5HWR3 Cluster: 50S ribosomal protein L11 0.17 0.0865 1.9E-01 4.6E-01 -0.1386 3.3E-01 -0.0248 5.2E-01 -0.0235 8.5E-01 0.1164 1.6E-01 Roseburia_hominis UniRef90_D4JN77 Cluster: HTH cro/C1-type domain-containing protein 0.22 0.0174 1.9E-01 4.6E-01 -0.0182 5.6E-01 -0.0026 7.4E-01 0.0169 5.2E-01 -0.0088 6.1E-01 Roseburia_hominis UniRef90_G2T592 Cluster: Transport permease protein 0.12 0.0499 1.9E-01 4.6E-01 -0.0028 9.7E-01 0.0128 5.7E-01 0.0467 5.1E-01 0.0800 9.8E-02 Roseburia_hominis UniRef90_G2SXN5 Cluster: UPF0122 protein DWX93_11955 0.10 0.0560 1.9E-01 4.7E-01 -0.1452 1.3E-01 -0.0402 1.1E-01 -0.0293 7.1E-01 0.0355 5.2E-01 Roseburia_hominis UniRef90_R5UJE0 Cluster: Chaperone protein DnaK 0.28 0.0620 1.9E-01 4.7E-01 -0.0394 7.1E-01 -0.0151 5.8E-01 -0.1105 2.2E-01 0.0507 3.9E-01 Roseburia_hominis UniRef90_G2T138 Cluster: RNA polymerase sigma factor SigA 0.16 0.0525 1.9E-01 4.7E-01 -0.0783 3.9E-01 -0.0056 8.2E-01 0.0124 8.7E-01 0.0229 6.5E-01 Roseburia_hominis UniRef90_C4ZB96 Cluster: 30S ribosomal protein S12 0.26 0.0857 2.0E-01 4.7E-01 -0.0527 7.2E-01 -0.0117 7.6E-01 0.0104 9.3E-01 0.1236 1.4E-01 Roseburia_hominis UniRef90_C4ZBS6 Cluster: 50S ribosomal protein L16 0.22 0.0933 2.0E-01 4.8E-01 -0.1359 4.1E-01 -0.0631 1.3E-01 -0.0088 9.5E-01 -0.0375 6.8E-01 Roseburia_hominis UniRef90_G2SXH2 Cluster: UDP-N-acetylmuramoyl-L-alanyl-D-glutamate--2,6- 0.11 0.0364 2.0E-01 4.8E-01 -0.0683 2.8E-01 -0.0234 1.6E-01 -0.0065 9.0E-01 0.0168 6.4E-01 diaminopimelate ligase 58

Supplementary Data 3b UniRef90 Family Plasma TMAO Red meat Red meat Choline Choline Species Cluster Name Detection member ID Rate Effect P FDR Effect P Effect P Effect P Effect P Roseburia_hominis UniRef90_G2SYJ7 Cluster: Threonine--tRNA ligase 0.12 0.0362 2.0E-01 4.8E-01 -0.0472 4.5E-01 -0.0070 6.8E-01 0.0217 6.8E-01 0.0257 4.8E-01 Roseburia_hominis UniRef90_G2SZA0 Cluster: Methyl-accepting chemotaxis protein 0.12 0.0335 2.0E-01 4.8E-01 -0.0274 6.4E-01 -0.0137 3.7E-01 0.0284 5.5E-01 0.0132 6.9E-01 Roseburia_hominis UniRef90_G2T306 Cluster: Ion-translocating oxidoreductase complex subunit E 0.14 0.0583 2.1E-01 4.8E-01 -0.0011 9.9E-01 -0.0269 3.2E-01 0.0305 7.2E-01 0.0467 4.3E-01 Roseburia_hominis UniRef90_G2SXA5 Cluster: Crotonobetaine/carnitine-CoA ligase 0.12 0.0473 2.1E-01 4.8E-01 0.0767 3.6E-01 0.0246 2.7E-01 0.0525 4.5E-01 0.0604 2.1E-01 Roseburia_hominis UniRef90_D4MXT9 Cluster: Phage_integrase domain-containing protein 0.15 0.0141 2.1E-01 4.8E-01 -0.0151 5.6E-01 -0.0009 9.0E-01 0.0088 6.9E-01 0.0213 1.4E-01 Roseburia_hominis UniRef90_D4LLF7 Cluster: Cardiolipin synthase 0.12 0.0047 2.1E-01 4.8E-01 0.0023 7.9E-01 0.0001 9.5E-01 -0.0038 6.0E-01 0.0064 1.8E-01 Roseburia_hominis UniRef90_G2T198 Cluster: Transketolase family protein 0.15 0.0585 2.1E-01 4.9E-01 -0.0271 7.9E-01 -0.0092 7.4E-01 -0.0421 6.3E-01 0.0486 4.2E-01 Roseburia_hominis UniRef90_D4KLS6 Cluster: Anaerobic sulfatase-maturating enzyme 0.17 0.0498 2.1E-01 4.9E-01 0.0548 5.3E-01 -0.0469 4.5E-02 0.0343 6.4E-01 0.0235 6.4E-01 Roseburia_hominis UniRef90_G2T1H9 Cluster: Cell shape-determining protein MreC 0.11 0.0501 2.2E-01 4.9E-01 -0.0288 7.4E-01 0.0068 7.8E-01 -0.0341 6.5E-01 0.0747 1.5E-01 Roseburia_hominis UniRef90_G2T313 Cluster: 4-hydroxy-3-methylbut-2-enyl diphosphate reductase 0.14 0.0554 2.2E-01 4.9E-01 -0.1543 1.1E-01 -0.0268 3.1E-01 -0.0305 7.1E-01 0.1102 5.4E-02 Roseburia_hominis UniRef90_G2T243 Cluster: Multi-sensor hybrid histidine kinase 0.11 0.0271 2.2E-01 4.9E-01 -0.0799 1.0E-01 -0.0272 3.7E-02 -0.0296 4.7E-01 0.0288 3.1E-01 Roseburia_hominis UniRef90_C4ZCE7 Cluster: Aspartate-semialdehyde dehydrogenase 0.10 0.0417 2.2E-01 4.9E-01 -0.1288 8.4E-02 -0.0193 3.4E-01 0.0473 4.5E-01 0.0631 1.5E-01 Roseburia_hominis UniRef90_D4KLI2 Cluster: Phosphoglucosamine mutase 0.13 0.0487 2.2E-01 4.9E-01 -0.1091 2.2E-01 -0.0405 8.2E-02 -0.0100 8.9E-01 0.0329 5.1E-01 Roseburia_hominis UniRef90_G2T414 Cluster: Asparagine--tRNA ligase 0.14 0.0411 2.2E-01 4.9E-01 -0.1104 1.4E-01 -0.0182 3.7E-01 -0.0307 6.3E-01 0.0058 8.9E-01 Roseburia_hominis UniRef90_G2T1X6 Cluster: Nucleotide-binding protein RHOM_02490 0.12 0.0476 2.2E-01 5.0E-01 0.0120 8.9E-01 0.0085 7.1E-01 -0.0744 3.0E-01 0.0726 1.4E-01 Roseburia_hominis UniRef90_G2SYR1 Cluster: Site-specific recombinase XerD 0.14 0.0349 2.2E-01 5.0E-01 0.0044 9.4E-01 -0.0166 3.2E-01 0.0695 2.0E-01 0.0186 6.1E-01 Roseburia_hominis UniRef90_G2T2Y2 Cluster: Uronate isomerase 0.14 0.0526 2.3E-01 5.0E-01 -0.0496 6.1E-01 -0.0075 7.7E-01 -0.0053 9.5E-01 0.0942 8.8E-02 Roseburia_hominis UniRef90_G2T2X6 Cluster: ABC transporter substrate-binding protein 0.19 0.0737 2.3E-01 5.0E-01 -0.1109 4.2E-01 -0.0086 8.2E-01 0.1343 2.5E-01 0.1608 4.3E-02 Roseburia_hominis UniRef90_G2SXA2 Cluster: CoA transferase 0.11 0.0448 2.3E-01 5.0E-01 0.0402 6.2E-01 -0.0021 9.2E-01 0.0322 6.4E-01 0.0358 4.5E-01 Roseburia_hominis UniRef90_G2T0P3 Cluster: Binding-protein-dependent transport systems inner membrane 0.13 0.0496 2.3E-01 5.0E-01 0.0314 7.3E-01 -0.0362 1.3E-01 0.0233 7.6E-01 0.0682 1.9E-01 component Roseburia_hominis UniRef90_P0A3Y6 Cluster: Aminoglycoside 3'-phosphotransferase 0.13 0.0382 2.3E-01 5.0E-01 -0.0588 4.0E-01 -0.0019 9.2E-01 -0.0569 3.4E-01 -0.0010 9.8E-01 Roseburia_hominis UniRef90_G2T0S6 Cluster: ABC transporter substrate-binding protein 0.20 0.0711 2.4E-01 5.1E-01 -0.1443 2.8E-01 -0.0447 2.1E-01 0.0698 5.4E-01 0.0859 2.6E-01 Roseburia_hominis UniRef90_G2T3F1 Cluster: Flagellar biosynthetic protein FliR 0.11 0.0495 2.4E-01 5.1E-01 0.0116 9.0E-01 -0.0162 5.1E-01 0.0759 3.4E-01 0.0552 3.0E-01 Roseburia_hominis UniRef90_G2T4W1 Cluster: Lysine--tRNA ligase 0.21 0.0418 2.5E-01 5.2E-01 -0.0538 5.0E-01 -0.0130 5.3E-01 -0.0818 2.2E-01 0.0357 4.3E-01 Roseburia_hominis UniRef90_G2T447 Cluster: Glycosyl transferase family 2 0.12 0.0478 2.5E-01 5.2E-01 -0.1689 7.1E-02 -0.0380 1.2E-01 0.0179 8.2E-01 0.0564 2.8E-01 Roseburia_hominis UniRef90_R5HXI3 Cluster: 50S ribosomal protein L1 0.23 0.0657 2.5E-01 5.2E-01 -0.2537 4.8E-02 -0.0766 2.1E-02 -0.0061 9.5E-01 0.1080 1.3E-01 Roseburia_hominis UniRef90_G2T5L7 Cluster: 50S ribosomal protein L6 0.26 0.0885 2.5E-01 5.2E-01 -0.0403 8.1E-01 -0.0016 9.7E-01 -0.1460 3.1E-01 0.1248 2.0E-01 Roseburia_hominis UniRef90_D4KKC1 Cluster: NADH peroxidase 0.18 0.0799 2.6E-01 5.3E-01 -0.2857 7.0E-02 -0.0388 3.5E-01 -0.0367 7.8E-01 -0.0218 8.1E-01 Roseburia_hominis UniRef90_G2SXA1 Cluster: CoA transferase 0.11 0.0455 2.6E-01 5.3E-01 0.0331 7.1E-01 -0.0243 3.0E-01 0.0358 6.4E-01 -0.0251 6.2E-01 Roseburia_hominis UniRef90_G2T3D9 Cluster: Basal-body rod modification protein FlgD 0.18 0.0715 2.7E-01 5.4E-01 -0.2724 6.0E-02 -0.0292 4.4E-01 -0.0316 7.9E-01 -0.0199 8.1E-01 Roseburia_hominis UniRef90_G2T1K2 Cluster: Formate--tetrahydrofolate ligase 0.13 0.0369 2.7E-01 5.4E-01 -0.0658 3.9E-01 -0.0074 7.1E-01 -0.0174 7.8E-01 0.0264 5.3E-01 Roseburia_hominis UniRef90_R5ZK06 Cluster: Fructose-1,6-bisphosphate aldolase, class II 0.21 0.0628 2.7E-01 5.4E-01 -0.1282 3.1E-01 -0.0505 1.3E-01 -0.0165 8.8E-01 0.1015 1.6E-01 Roseburia_hominis UniRef90_D4L2B7 Cluster: Glucose-1-phosphate thymidylyltransferase 0.11 0.0386 2.8E-01 5.4E-01 0.0210 7.9E-01 0.0056 7.9E-01 0.0091 8.9E-01 0.0187 6.8E-01 Roseburia_hominis UniRef90_G2T391 Cluster: Recombinase domain-containing protein 0.21 0.0153 2.8E-01 5.4E-01 -0.0074 8.1E-01 -0.0069 4.0E-01 -0.0133 6.1E-01 0.0002 9.9E-01 Roseburia_hominis UniRef90_G2T5N2 Cluster: 50S ribosomal protein L4 0.20 0.0774 2.8E-01 5.4E-01 -0.1026 5.2E-01 -0.0402 3.3E-01 0.0797 5.5E-01 0.1085 2.2E-01 Roseburia_hominis UniRef90_D4M5L4 Cluster: 30S ribosomal protein S21 0.12 0.0572 2.8E-01 5.4E-01 -0.0603 6.1E-01 0.0002 9.9E-01 -0.0465 6.4E-01 0.0931 1.7E-01 Roseburia_hominis UniRef90_G2T155 Cluster: Hemerythrin 0.12 0.0494 2.8E-01 5.5E-01 -0.2732 8.9E-03 -0.0330 2.3E-01 0.0603 4.9E-01 0.0055 9.3E-01 Roseburia_hominis UniRef90_G2T319 Cluster: Glutaconyl-CoA decarboxylase subunit beta 0.20 0.0543 2.8E-01 5.5E-01 -0.0793 4.7E-01 -0.0472 1.1E-01 -0.0280 7.6E-01 0.0223 7.3E-01 Roseburia_hominis UniRef90_G2SZR5 Cluster: SSD domain-containing protein 0.12 0.0387 2.8E-01 5.5E-01 0.0369 6.5E-01 -0.0351 9.4E-02 -0.0072 9.1E-01 0.0465 3.0E-01 Roseburia_hominis UniRef90_G2SZ75 Cluster: 50S ribosomal protein L33 0.13 0.0537 2.8E-01 5.5E-01 -0.1155 2.9E-01 -0.0274 3.5E-01 0.0025 9.8E-01 0.0559 3.8E-01 Roseburia_hominis UniRef90_G2T308 Cluster: Ion-translocating oxidoreductase complex subunit D 0.13 0.0477 2.9E-01 5.6E-01 -0.0720 4.9E-01 -0.0116 6.7E-01 0.0729 4.0E-01 0.0621 2.9E-01 Roseburia_hominis UniRef90_G2SZD7 Cluster: Methyl-accepting transducer domain-containing protein 0.13 0.0332 2.9E-01 5.6E-01 -0.0043 9.5E-01 -0.0011 9.5E-01 -0.0067 9.1E-01 0.0690 8.5E-02 Roseburia_hominis UniRef90_R5HNB3 Cluster: Replicative DNA helicase 0.11 0.0317 2.9E-01 5.6E-01 -0.0220 7.5E-01 -0.0049 7.9E-01 -0.0060 9.2E-01 0.0618 1.2E-01 Roseburia_hominis UniRef90_G2T148 Cluster: Chaperone protein DnaJ 0.10 0.0330 2.9E-01 5.6E-01 -0.0605 3.9E-01 -0.0111 5.4E-01 -0.0284 6.3E-01 0.0206 6.1E-01 Roseburia_hominis UniRef90_G2SXK1 Cluster: CBS domain-containing protein 0.13 0.0536 3.0E-01 5.6E-01 -0.0803 4.8E-01 -0.0185 5.4E-01 0.1271 1.9E-01 0.1045 1.1E-01 Roseburia_hominis UniRef90_G2T2S9 Cluster: Methyl-accepting chemotaxis protein 0.10 0.0258 3.0E-01 5.6E-01 -0.0737 1.9E-01 -0.0074 6.3E-01 -0.0012 9.8E-01 0.0366 2.7E-01 Roseburia_hominis UniRef90_G2T0N6 Cluster: Binding-protein-dependent transport systems inner membrane 0.11 0.0300 3.0E-01 5.7E-01 -0.0964 1.3E-01 -0.0161 3.6E-01 0.0029 9.6E-01 0.0749 4.5E-02 component Roseburia_hominis UniRef90_G2T2S3 Cluster: Methyl-accepting chemotaxis protein 0.14 0.0403 3.1E-01 5.8E-01 -0.1574 7.1E-02 -0.0127 5.9E-01 0.0724 3.2E-01 0.0626 2.2E-01 Roseburia_hominis UniRef90_G2T0S8 Cluster: Carbohydrate ABC transporter permease 0.11 0.0414 3.2E-01 5.8E-01 -0.0318 7.3E-01 -0.0222 3.6E-01 0.0098 9.0E-01 0.0616 2.4E-01 Roseburia_hominis UniRef90_G2T5X8 Cluster: Histidine kinase 0.12 0.0215 3.2E-01 5.8E-01 -0.0765 1.1E-01 -0.0181 1.6E-01 -0.0573 1.4E-01 0.0224 4.2E-01 Roseburia_hominis UniRef90_G2SXB2 Cluster: Peptide chain release factor 1 0.12 0.0300 3.2E-01 5.8E-01 -0.1164 7.9E-02 -0.0127 4.8E-01 -0.0536 3.4E-01 0.0549 1.5E-01 Roseburia_hominis UniRef90_G2T4B8 Cluster: Shikimate dehydrogenase (NADP(+)) 0.10 0.0341 3.2E-01 5.8E-01 -0.1604 3.1E-02 -0.0305 1.3E-01 0.0466 4.7E-01 0.0379 3.9E-01 Roseburia_hominis UniRef90_G2T3M7 Cluster: ABC transporter permease 0.13 0.0372 3.2E-01 5.8E-01 -0.0016 9.8E-01 -0.0246 2.7E-01 0.0080 9.1E-01 0.0458 3.4E-01 Roseburia_hominis UniRef90_G2SWR4 Cluster: Gate domain-containing protein 0.11 0.0353 3.3E-01 5.8E-01 -0.1247 1.2E-01 -0.0299 1.6E-01 0.0339 6.2E-01 0.0086 8.5E-01 Roseburia_hominis UniRef90_G2T3G3 Cluster: RNA polymerase sigma factor 0.11 0.0396 3.3E-01 5.8E-01 -0.0166 8.5E-01 -0.0218 3.6E-01 -0.0351 6.4E-01 0.0825 1.0E-01 Roseburia_hominis UniRef90_G2T2N6 Cluster: Recombinase domain-containing protein 0.29 0.0082 3.3E-01 5.8E-01 -0.0169 3.6E-01 -0.0072 1.4E-01 -0.0036 8.2E-01 0.0036 7.3E-01 Roseburia_hominis UniRef90_C4Z926 Cluster: Threonine ammonia-lyase 0.13 0.0348 3.3E-01 5.9E-01 0.0230 7.7E-01 0.0043 8.4E-01 0.0207 7.5E-01 0.0262 5.6E-01 Roseburia_hominis UniRef90_G2SWY9 Cluster: Peptide chain release factor 3 0.11 0.0276 3.3E-01 5.9E-01 -0.0514 4.1E-01 -0.0239 1.6E-01 0.0050 9.2E-01 0.0213 5.6E-01 Roseburia_hominis UniRef90_G2SWP8 Cluster: Oligoendopeptidase F 0.10 0.0231 3.3E-01 5.9E-01 -0.0635 2.2E-01 0.0024 8.7E-01 -0.0139 7.5E-01 0.0725 1.8E-02 Roseburia_hominis UniRef90_G2T0S7 Cluster: Sugar ABC transporter permease 0.11 0.0385 3.4E-01 5.9E-01 -0.0353 7.0E-01 -0.0121 6.2E-01 0.0441 5.7E-01 0.0723 1.6E-01 Roseburia_hominis UniRef90_G2SYH5 Cluster: MCP signaling domain-containing protein 0.12 0.0423 3.4E-01 5.9E-01 -0.0917 3.5E-01 -0.0110 6.7E-01 -0.0687 4.0E-01 0.0229 6.8E-01 Roseburia_hominis UniRef90_G2T204 Cluster: Binding-protein-dependent transport systems inner membrane 0.16 0.0547 3.4E-01 6.0E-01 -0.3133 1.3E-02 -0.0427 2.1E-01 -0.0747 4.9E-01 0.0574 4.4E-01 component Roseburia_hominis UniRef90_G2T3D7 Cluster: MgtE_N domain-containing protein 0.13 0.0401 3.5E-01 6.0E-01 -0.0378 6.9E-01 -0.0147 5.6E-01 -0.0319 6.9E-01 0.0348 5.2E-01 Roseburia_hominis UniRef90_G2T4M2 Cluster: Ferric uptake regulator family protein 0.11 0.0516 3.5E-01 6.0E-01 -0.1592 2.0E-01 -0.0400 2.3E-01 -0.0512 6.3E-01 -0.0018 9.8E-01 Roseburia_hominis UniRef90_G2SX78 Cluster: Hydrogenase accessory protein HypB 0.13 0.0536 3.6E-01 6.0E-01 -0.1413 2.8E-01 -0.0578 8.6E-02 -0.0102 9.3E-01 0.0608 4.1E-01 Roseburia_hominis UniRef90_D4KJW6 Cluster: Triosephosphate isomerase 0.19 0.0588 3.6E-01 6.0E-01 0.0178 9.0E-01 -0.0075 8.4E-01 0.0994 4.1E-01 0.1274 1.1E-01 Roseburia_hominis UniRef90_G2T516 Cluster: Methyl-accepting chemotaxis sensory transducer 0.14 0.0373 3.6E-01 6.1E-01 -0.1138 2.1E-01 -0.0371 1.3E-01 -0.0759 3.2E-01 -0.0248 6.4E-01 Roseburia_hominis UniRef90_G2T234 Cluster: Cadmium-translocating P-type ATPase 0.11 0.0270 3.7E-01 6.1E-01 -0.0447 5.0E-01 0.0064 7.2E-01 -0.0061 9.1E-01 0.0302 4.3E-01 Roseburia_hominis UniRef90_G2SXD6 Cluster: CPBP family intramembrane metalloprotease 0.10 0.0297 3.7E-01 6.1E-01 -0.0903 2.1E-01 0.0039 8.4E-01 -0.0086 8.9E-01 0.0454 2.7E-01 Roseburia_hominis UniRef90_G2T2X4 Cluster: Binding-protein-dependent transporters inner membrane 0.13 0.0390 3.7E-01 6.1E-01 -0.0322 7.4E-01 0.0048 8.5E-01 0.0351 6.7E-01 0.0912 1.1E-01 Roseburia_hominis UniRef90_G2T2R0 Cluster:component Catabolite control protein A 0.13 0.0432 3.8E-01 6.2E-01 -0.0017 9.9E-01 0.0215 4.6E-01 -0.1390 1.3E-01 0.0529 4.0E-01 Roseburia_hominis UniRef90_G2SWN9 Cluster: L-ribulokinase (Putative) 0.12 0.0254 3.8E-01 6.2E-01 -0.0513 4.2E-01 -0.0086 6.1E-01 -0.0618 2.5E-01 -0.0305 4.1E-01 Roseburia_hominis UniRef90_C4Z240 Cluster: Flagellar hook-associated protein 2 C-terminus 0.15 0.0316 3.8E-01 6.2E-01 -0.1649 5.1E-02 -0.0503 1.6E-02 -0.0506 4.8E-01 0.0231 6.1E-01 Roseburia_hominis UniRef90_G2SYZ6 Cluster: ATP-dependent zinc metalloprotease FtsH 0.10 0.0221 3.9E-01 6.2E-01 -0.0101 8.6E-01 -0.0022 8.8E-01 0.0243 6.1E-01 0.0268 4.1E-01 Roseburia_hominis UniRef90_G2SXW3 Cluster: Glycoside hydrolase family 2 0.10 0.0199 3.9E-01 6.3E-01 -0.0713 1.7E-01 -0.0038 7.8E-01 -0.0132 7.6E-01 0.0092 7.6E-01 Roseburia_hominis UniRef90_G2T3E2 Cluster: Motility protein A 0.17 0.0539 3.9E-01 6.3E-01 -0.0913 5.1E-01 -0.0096 7.9E-01 0.0515 6.6E-01 0.1103 1.6E-01 Roseburia_hominis UniRef90_D4KQF8 Cluster: GTP-sensing transcriptional pleiotropic repressor CodY 0.14 0.0416 3.9E-01 6.3E-01 -0.0772 4.7E-01 -0.0213 4.6E-01 0.1067 2.3E-01 0.1032 9.7E-02 Roseburia_hominis UniRef90_R5QD19 Cluster: ATP-binding protein 0.12 0.0066 4.1E-01 6.5E-01 0.0190 2.9E-01 -0.0062 1.9E-01 -0.0037 8.1E-01 0.0039 7.0E-01 Roseburia_hominis UniRef90_G2T3D4 Cluster: Flagellar biosynthesis/type III secretory pathway protein 0.12 0.0331 4.1E-01 6.5E-01 -0.1085 2.3E-01 -0.0258 2.8E-01 0.0145 8.4E-01 0.0453 3.8E-01 Roseburia_hominis UniRef90_G2SZJ8 Cluster: Flagellar hook-associated protein FlgK 0.20 0.0428 4.1E-01 6.5E-01 -0.0394 7.4E-01 -0.0246 4.2E-01 0.0898 3.7E-01 0.1000 1.3E-01 Roseburia_hominis UniRef90_G2T5C3 Cluster: Toxin-antitoxin system protein 0.11 0.0077 4.2E-01 6.5E-01 0.0119 5.6E-01 -0.0021 7.0E-01 -0.0312 7.4E-02 -0.0059 6.2E-01 Roseburia_hominis UniRef90_G2T609 Cluster: ATP synthase subunit a 0.17 0.0493 4.2E-01 6.5E-01 -0.1044 4.4E-01 0.0025 9.5E-01 0.0574 6.1E-01 0.0794 3.1E-01 Roseburia_hominis UniRef90_D4JMV4 Cluster: Tyrosine recombinase XerC 0.23 0.0094 4.2E-01 6.5E-01 -0.0395 1.3E-01 -0.0114 8.8E-02 -0.0065 7.7E-01 0.0032 8.2E-01 Roseburia_hominis UniRef90_G2T140 Cluster: Uridine kinase 0.13 0.0258 4.2E-01 6.6E-01 -0.0257 7.2E-01 0.0006 9.8E-01 0.0295 6.2E-01 0.0700 9.1E-02 Roseburia_hominis UniRef90_G2SXB0 Cluster: Steryl acetyl hydrolase 0.11 0.0314 4.3E-01 6.6E-01 0.0540 5.3E-01 -0.0181 4.4E-01 0.0022 9.8E-01 -0.0297 5.6E-01 Roseburia_hominis UniRef90_G2SY77 Cluster: Methyl-accepting chemotaxis sensory transducer 0.13 0.0228 4.3E-01 6.6E-01 0.0082 9.0E-01 -0.0126 4.6E-01 0.0586 2.8E-01 0.0214 5.6E-01 Roseburia_hominis UniRef90_G2T1A0 Cluster: Aldose 1-epimerase 0.17 0.0425 4.3E-01 6.6E-01 0.0126 9.2E-01 -0.0055 8.6E-01 -0.0837 4.1E-01 0.0396 5.6E-01 Roseburia_hominis UniRef90_G2T4Z8 Cluster: Response regulator receiver modulated diguanylate 0.10 0.0184 4.3E-01 6.6E-01 -0.0633 2.2E-01 0.0028 8.4E-01 0.0153 7.2E-01 0.0299 3.1E-01 cyclase/phosphodiesterase Roseburia_hominis UniRef90_G2T002 Cluster: Band_7_1 domain-containing protein 0.10 0.0216 4.3E-01 6.6E-01 0.0098 8.7E-01 0.0015 9.3E-01 -0.0044 9.3E-01 0.0704 4.8E-02 Roseburia_hominis UniRef90_G2T137 Cluster: DNA primase 0.10 0.0200 4.3E-01 6.6E-01 -0.0702 2.2E-01 -0.0179 2.3E-01 -0.0079 8.7E-01 0.0092 7.8E-01 59

Supplementary Data 3b UniRef90 Family Plasma TMAO Red meat Red meat Choline Choline Species Cluster Name Detection member ID Rate Effect P FDR Effect P Effect P Effect P Effect P Roseburia_hominis UniRef90_G2T506 Cluster: DNA polymerase III, delta prime subunit 0.10 0.0252 4.3E-01 6.6E-01 -0.0405 5.7E-01 -0.0292 1.2E-01 0.0437 4.7E-01 0.0374 3.5E-01 Roseburia_hominis UniRef90_G2T449 Cluster: Undecaprenyl-phosphate glucose phosphotransferase 0.17 0.0378 4.4E-01 6.6E-01 -0.0750 4.8E-01 -0.0538 5.8E-02 0.0203 8.2E-01 0.0556 3.6E-01 Roseburia_hominis UniRef90_G2T307 Cluster: Ion-translocating oxidoreductase complex subunit G 0.13 0.0397 4.4E-01 6.6E-01 -0.1407 2.2E-01 -0.0270 3.7E-01 0.0094 9.2E-01 0.0304 6.4E-01 Roseburia_hominis UniRef90_G2T2Q9 Cluster: Carbohydrate ABC transporter permease 0.10 0.0305 4.4E-01 6.6E-01 -0.0073 9.3E-01 0.0274 2.3E-01 0.0665 3.6E-01 0.1036 3.5E-02 Roseburia_hominis UniRef90_C4Z798 Cluster: Thioredoxin domain-containing protein 0.14 0.0072 4.4E-01 6.6E-01 0.0020 9.2E-01 0.0052 3.6E-01 0.0031 8.6E-01 0.0119 3.3E-01 Roseburia_hominis UniRef90_G2SXQ0 Cluster: Acetate kinase 0.13 0.0295 4.4E-01 6.7E-01 -0.0772 3.6E-01 -0.0297 1.9E-01 -0.0047 9.5E-01 0.1237 1.1E-02 Roseburia_hominis UniRef90_R5HMA7 Cluster: 3-isopropylmalate dehydratase large subunit 0.10 0.0233 4.5E-01 6.7E-01 -0.1302 5.6E-02 -0.0094 6.0E-01 -0.0071 9.0E-01 0.0503 2.0E-01 Roseburia_hominis UniRef90_G2T304 Cluster: Ion-translocating oxidoreductase complex subunit B 0.15 0.0372 4.6E-01 6.8E-01 -0.0756 4.9E-01 -0.0484 9.9E-02 -0.0272 7.7E-01 0.0111 8.6E-01 Roseburia_hominis UniRef90_G2T5B2 Cluster: Flagellar basal body protein 0.15 0.0343 4.6E-01 6.8E-01 -0.1123 2.7E-01 -0.0581 3.3E-02 0.0373 6.6E-01 0.0043 9.4E-01 Roseburia_hominis UniRef90_D4KKC7 Cluster: Phosphate acetyltransferase 0.15 0.0295 4.6E-01 6.8E-01 -0.1427 1.0E-01 -0.0221 3.4E-01 -0.0457 5.3E-01 0.0129 8.0E-01 Roseburia_hominis UniRef90_G2SWP0 Cluster: L-arabinose isomerase 0.18 0.0321 4.6E-01 6.8E-01 -0.1118 2.4E-01 -0.0201 4.3E-01 -0.0671 4.0E-01 -0.0208 7.1E-01 Roseburia_hominis UniRef90_D4KUW2 Cluster: Branched-chain-amino-acid transaminase 0.11 0.0227 4.7E-01 6.9E-01 -0.0755 2.9E-01 -0.0403 3.7E-02 0.0113 8.5E-01 0.0598 1.5E-01 Roseburia_hominis UniRef90_C4Z1K7 Cluster: Ketol-acid reductoisomerase (NADP(+)) 0.23 0.0369 4.7E-01 6.9E-01 -0.2006 7.4E-02 -0.0494 1.1E-01 0.0146 8.8E-01 0.0660 3.2E-01 Roseburia_hominis UniRef90_D4KQG3 Cluster: Flagellar motor switch protein FliG 0.15 0.0334 4.8E-01 7.0E-01 -0.1544 1.5E-01 -0.0229 4.0E-01 0.0356 6.9E-01 0.0488 4.1E-01 Roseburia_hominis UniRef90_G2T000 Cluster: Peptide chain release factor 2 0.17 0.0287 4.8E-01 7.0E-01 -0.0441 6.2E-01 -0.0215 3.7E-01 0.0100 8.9E-01 0.0366 4.8E-01 Roseburia_hominis UniRef90_C4Z639 Cluster: Bacteriophytochrome cph2 0.24 0.0104 4.9E-01 7.0E-01 0.0038 9.1E-01 -0.0067 4.7E-01 -0.0097 7.4E-01 0.0142 4.7E-01 Roseburia_hominis UniRef90_G2T5S9 Cluster: Cysteine synthase 0.13 0.0256 5.0E-01 7.1E-01 -0.0440 5.9E-01 -0.0026 9.1E-01 0.0140 8.4E-01 0.0249 6.0E-01 Roseburia_hominis UniRef90_G2SXX5 Cluster: Carbohydrate ABC transporter substrate-binding protein 0.11 0.0243 5.0E-01 7.2E-01 -0.0290 7.1E-01 -0.0399 6.1E-02 0.0145 8.3E-01 -0.0415 3.7E-01 Roseburia_hominis UniRef90_R6CT57 Cluster: 30S ribosomal protein S14 type Z 0.19 0.0378 5.0E-01 7.2E-01 0.0131 9.2E-01 -0.0094 7.8E-01 -0.0027 9.8E-01 -0.0090 9.0E-01 Roseburia_hominis UniRef90_G2SX96 Cluster: Electron transfer flavoprotein subunit alpha/FixB family protein 0.16 0.0407 5.1E-01 7.2E-01 0.1700 2.2E-01 0.0384 2.9E-01 0.0443 7.0E-01 0.0593 4.4E-01 Roseburia_hominis UniRef90_G2T3F7 Cluster: Protein-glutamate methylesterase/protein-glutamine glutaminase 0.16 0.0338 5.1E-01 7.2E-01 -0.0275 8.1E-01 0.0108 7.2E-01 0.0623 5.1E-01 0.0696 2.9E-01 Roseburia_hominis UniRef90_G2T523 Cluster: Diguanylate cyclase DosC 0.12 0.0090 5.2E-01 7.3E-01 -0.0347 3.3E-01 -0.0073 4.2E-01 -0.0311 3.0E-01 0.0259 1.8E-01 Roseburia_hominis UniRef90_G2SXE7 Cluster: Putative maltose/maltodextrin ABC transport system 0.12 0.0247 5.2E-01 7.4E-01 0.0052 9.5E-01 0.0042 8.6E-01 -0.0282 7.0E-01 0.0931 6.1E-02 Roseburia_hominis UniRef90_G2T1G1 Cluster: Diguanylate cyclase/phosphodiesterase 0.10 0.0134 5.4E-01 7.5E-01 -0.0722 1.4E-01 -0.0087 4.8E-01 0.0158 7.0E-01 -0.0036 8.9E-01 Roseburia_hominis UniRef90_G2T3Q9 Cluster: DNA repair protein RecN 0.13 0.0223 5.4E-01 7.5E-01 -0.1325 1.0E-01 -0.0129 5.5E-01 -0.1323 4.9E-02 0.0058 9.0E-01 Roseburia_hominis UniRef90_G2T5T7 Cluster: Bifunctional ligase/repressor BirA 0.11 0.0184 5.5E-01 7.6E-01 -0.0817 2.3E-01 -0.0199 2.7E-01 -0.0997 8.0E-02 0.0087 8.2E-01 Roseburia_hominis UniRef90_G2SXP7 Cluster: SdrD_B domain-containing protein 0.11 0.0203 5.5E-01 7.6E-01 0.0655 3.8E-01 -0.0286 1.5E-01 0.0412 5.2E-01 0.0689 1.1E-01 Roseburia_hominis UniRef90_G2T2E0 Cluster: ATP-binding cassette domain-containing protein 0.13 0.0171 5.5E-01 7.6E-01 -0.0065 9.2E-01 -0.0334 4.8E-02 0.0594 2.6E-01 0.0730 4.4E-02 Roseburia_hominis UniRef90_G2T621 Cluster: Membrane protein insertase YidC 0.13 0.0220 5.6E-01 7.6E-01 -0.0443 6.0E-01 -0.0302 1.7E-01 0.0311 6.6E-01 0.0530 2.6E-01 Roseburia_hominis UniRef90_G2T5A1 Cluster: Diadenylate cyclase 0.11 0.0218 5.6E-01 7.7E-01 -0.0762 3.5E-01 0.0075 7.4E-01 -0.0094 8.9E-01 0.0227 6.3E-01 Roseburia_hominis UniRef90_D4KQF0 Cluster: Glutamate--tRNA ligase 0.11 0.0153 5.6E-01 7.7E-01 -0.0574 3.3E-01 -0.0213 1.7E-01 -0.0332 5.0E-01 0.0138 6.8E-01 Roseburia_hominis UniRef90_G2SY94 Cluster: Hsp20/alpha crystallin family protein 0.10 0.0254 5.7E-01 7.7E-01 0.0290 7.7E-01 0.0059 8.2E-01 0.0893 2.9E-01 0.0346 5.4E-01 Roseburia_hominis UniRef90_G2T1U5 Cluster: DNA-binding protein 0.16 0.0402 5.7E-01 7.7E-01 -0.2356 1.3E-01 -0.0245 5.5E-01 0.0115 9.3E-01 0.0765 3.9E-01 Roseburia_hominis UniRef90_G2T3F3 Cluster: Flagellar biosynthesis protein FlhA 0.16 0.0227 5.7E-01 7.7E-01 -0.1226 1.7E-01 -0.0567 1.8E-02 -0.0818 2.9E-01 -0.0111 8.3E-01 Roseburia_hominis UniRef90_G2SXX8 Cluster: Alpha-galactosidase 0.12 -0.0166 5.7E-01 7.7E-01 -0.0342 6.0E-01 -0.0097 5.7E-01 -0.0127 8.2E-01 0.0066 8.6E-01 Roseburia_hominis UniRef90_D4KNA8 Cluster: Arabinose import ATP-binding protein AraG 0.15 0.0206 5.8E-01 7.8E-01 0.0760 3.5E-01 0.0034 8.7E-01 0.0576 4.0E-01 0.0720 1.2E-01 Roseburia_hominis UniRef90_G2T5Y6 Cluster: Metallophosphoesterase 0.14 0.0182 5.8E-01 7.8E-01 -0.0430 5.6E-01 -0.0408 3.3E-02 0.0359 5.7E-01 0.0114 7.8E-01 Roseburia_hominis UniRef90_C4Z640 Cluster: HAMP domain-containing protein 0.26 0.0111 6.0E-01 7.9E-01 0.0215 6.5E-01 0.0058 6.4E-01 -0.0135 7.4E-01 0.0291 2.7E-01 Roseburia_hominis UniRef90_D4KSS2 Cluster: Sugar diacid regulator 0.12 0.0170 6.0E-01 7.9E-01 0.0284 6.9E-01 -0.0107 5.7E-01 -0.0063 9.2E-01 0.0661 1.1E-01 Roseburia_hominis UniRef90_G2SX29 Cluster: Putative exonuclease of the beta-lactamase fold involved in RNA 0.12 0.0164 6.1E-01 7.9E-01 -0.0969 1.6E-01 -0.0018 9.2E-01 0.0197 7.4E-01 0.0359 3.7E-01 processing Roseburia_hominis UniRef90_G2T3N4 Cluster: Glycogen synthase 0.11 0.0141 6.1E-01 7.9E-01 -0.0420 4.8E-01 -0.0055 7.3E-01 0.0238 6.3E-01 0.0486 1.6E-01 Roseburia_hominis UniRef90_G2T5Z8 Cluster: PTS system, fructose-specific, IIABC component 0.11 0.0111 6.1E-01 7.9E-01 -0.0682 1.5E-01 -0.0334 7.9E-03 -0.0355 3.8E-01 -0.0022 9.4E-01 Roseburia_hominis UniRef90_G2SZF5 Cluster: DNA replication and repair protein RecF 0.11 0.0192 6.1E-01 8.0E-01 -0.1384 1.0E-01 -0.0033 8.8E-01 -0.1112 1.2E-01 -0.0052 9.1E-01 Roseburia_hominis UniRef90_G2T264 Cluster: Signaling protein 0.10 0.0123 6.1E-01 8.0E-01 -0.0394 4.6E-01 -0.0117 4.1E-01 -0.0386 3.9E-01 0.0205 5.0E-01 Roseburia_hominis UniRef90_G2T250 Cluster: Inner membrane ABC transporter permease protein ytfT 0.14 0.0236 6.2E-01 8.0E-01 -0.0915 3.9E-01 0.0001 1.0E+00 0.0477 5.9E-01 0.0752 2.1E-01 Roseburia_hominis UniRef90_G2T2G4 Cluster: 4-hydroxy-tetrahydrodipicolinate synthase 0.11 0.0210 6.2E-01 8.0E-01 -0.2382 1.2E-02 -0.0239 3.3E-01 0.0715 3.8E-01 -0.0005 9.9E-01 Roseburia_hominis UniRef90_G2SZ49 Cluster: Na/Pi-cotransporter II-related protein 0.11 0.0153 6.3E-01 8.0E-01 -0.1774 1.3E-02 -0.0362 5.4E-02 -0.0281 6.3E-01 0.0134 7.5E-01 Roseburia_hominis UniRef90_G2T042 Cluster: Uracil permease 0.10 0.0138 6.3E-01 8.1E-01 -0.0382 5.5E-01 -0.0099 5.6E-01 -0.0453 4.0E-01 0.0274 4.5E-01 Roseburia_hominis UniRef90_R6K6L3 Cluster: Glutamate dehydrogenase 0.17 0.0168 6.4E-01 8.1E-01 -0.0895 2.5E-01 -0.0125 5.6E-01 0.0610 3.6E-01 0.0897 5.0E-02 Roseburia_hominis UniRef90_D4KSZ4 Cluster: Antitoxin 0.11 -0.0082 6.5E-01 8.2E-01 -0.0013 9.7E-01 -0.0170 1.1E-01 -0.0209 5.3E-01 0.0147 5.2E-01 Roseburia_hominis UniRef90_G2T136 Cluster: Deoxyguanosinetriphosphate triphosphohydrolase-like protein 0.10 0.0142 6.5E-01 8.1E-01 -0.0683 3.1E-01 -0.0377 4.0E-02 0.0484 3.9E-01 0.0401 3.1E-01 Roseburia_hominis UniRef90_G2T441 Cluster: Pyrroline-5-carboxylate reductase 0.11 0.0179 6.6E-01 8.2E-01 -0.1040 2.5E-01 -0.0122 6.0E-01 0.1218 1.0E-01 0.1056 3.5E-02 Roseburia_hominis UniRef90_G2T2V4 Cluster: Methyl-accepting chemotaxis protein 0.12 0.0149 6.6E-01 8.2E-01 -0.0828 2.6E-01 -0.0110 5.8E-01 -0.0405 5.0E-01 -0.0064 8.8E-01 Roseburia_hominis UniRef90_D4L2B6 Cluster: dTDP-glucose 4,6-dehydratase 0.17 0.0191 6.6E-01 8.2E-01 -0.0472 6.2E-01 -0.0436 8.6E-02 -0.0229 7.8E-01 -0.0143 7.9E-01 Roseburia_hominis UniRef90_D4K7L5 Cluster: Cardiolipin synthase 0.19 0.0026 6.6E-01 8.3E-01 -0.0006 9.6E-01 -0.0003 9.4E-01 0.0042 7.2E-01 0.0152 4.3E-02 Roseburia_hominis UniRef90_D4L1I9 Cluster: Uracil phosphoribosyltransferase 0.10 -0.0148 6.8E-01 8.3E-01 0.0022 9.8E-01 -0.0203 3.3E-01 0.0149 8.3E-01 0.0448 3.2E-01 Roseburia_hominis UniRef90_G2T0N7 Cluster: Oligopeptide/dipeptide ABC transporter, ATP-binding protein 0.13 0.0128 6.9E-01 8.4E-01 -0.0439 5.3E-01 -0.0326 7.7E-02 -0.0044 9.4E-01 -0.0053 9.0E-01 Roseburia_hominis UniRef90_G2T3H7 Cluster:domain Uridylate kinase 0.12 0.0154 7.0E-01 8.5E-01 -0.1558 7.7E-02 -0.0475 4.7E-02 -0.0134 8.6E-01 0.0438 4.0E-01 Roseburia_hominis UniRef90_G2T1V5 Cluster: ATP-dependent zinc metalloprotease FtsH 0.16 0.0122 7.1E-01 8.5E-01 0.0039 9.6E-01 -0.0105 5.8E-01 -0.0287 6.2E-01 0.0405 3.1E-01 Roseburia_hominis UniRef90_G2SXA7 Cluster: Acetylesterase 0.15 0.0231 7.1E-01 8.5E-01 0.0542 6.9E-01 -0.0077 8.3E-01 0.0810 4.7E-01 -0.0082 9.2E-01 Roseburia_hominis UniRef90_D4L022 Cluster: M18 family aminopeptidase 0.14 0.0142 7.1E-01 8.5E-01 0.0538 5.3E-01 -0.0155 5.0E-01 -0.0107 8.8E-01 0.0447 3.7E-01 Roseburia_hominis UniRef90_C4Z797 Cluster: UPF0246 protein ERS852406_00003 0.14 0.0027 7.1E-01 8.5E-01 0.0127 4.2E-01 -0.0021 6.2E-01 0.0022 8.7E-01 0.0081 3.7E-01 Roseburia_hominis UniRef90_D4LY53 Cluster: Transcriptional regulator 0.15 0.0119 7.3E-01 8.6E-01 -0.0545 4.9E-01 0.0040 8.4E-01 -0.0093 8.9E-01 0.0492 2.5E-01 Roseburia_hominis UniRef90_G2T199 Cluster: L-ribulose-5-phosphate 4-epimerase 0.11 0.0140 7.4E-01 8.7E-01 -0.0413 6.6E-01 -0.0190 4.3E-01 -0.0187 8.1E-01 0.0158 7.6E-01 Roseburia_hominis UniRef90_G2T3Q7 Cluster: Sensory transduction system regulatory protein 0.11 0.0107 7.4E-01 8.7E-01 -0.1565 3.1E-02 -0.0192 3.2E-01 -0.0800 1.9E-01 -0.0012 9.8E-01 Roseburia_hominis UniRef90_G2T1X3 Cluster: HPr kinase/phosphorylase 0.11 0.0102 7.6E-01 8.8E-01 -0.0370 6.1E-01 -0.0145 4.5E-01 0.0490 4.2E-01 -0.0081 8.4E-01 Roseburia_hominis UniRef90_G2T442 Cluster: Cyclomaltodextrinase 0.10 -0.0091 7.7E-01 8.8E-01 -0.0620 3.7E-01 -0.0197 2.8E-01 0.0088 8.8E-01 -0.0014 9.7E-01 Roseburia_hominis UniRef90_D4J5R9 Cluster: Alkaline phosphatase synthesis sensor protein phoR 0.14 0.0025 7.7E-01 8.8E-01 0.0054 7.8E-01 0.0069 1.7E-01 0.0011 9.5E-01 0.0136 2.1E-01 Roseburia_hominis UniRef90_D5HH09 Cluster: H+ Antiporter protein 0.10 -0.0058 7.8E-01 8.9E-01 -0.0429 3.7E-01 0.0073 5.5E-01 -0.0101 8.0E-01 0.0403 1.2E-01 Roseburia_hominis UniRef90_C4Z753 Cluster: Choloylglycine hydrolase 0.24 0.0042 7.8E-01 8.9E-01 0.0205 5.4E-01 0.0021 8.2E-01 -0.0119 6.7E-01 0.0269 1.6E-01 Roseburia_hominis UniRef90_G2SX40 Cluster: Ribosomal RNA small subunit methyltransferase H 0.10 0.0091 7.9E-01 8.9E-01 -0.0509 5.0E-01 -0.0151 4.6E-01 0.0143 8.2E-01 0.0392 3.7E-01 Roseburia_hominis UniRef90_G2T121 Cluster: Probable multidrug resistance ABC transporter ATP- 0.11 0.0063 7.9E-01 8.9E-01 0.0020 9.7E-01 -0.0113 4.2E-01 0.0238 5.9E-01 0.0305 3.1E-01 binding/permease protein YheH Roseburia_hominis UniRef90_G2T3M8 Cluster: ABC transporter related protein 0.15 0.0101 8.0E-01 8.9E-01 -0.1035 2.3E-01 -0.0301 1.8E-01 -0.0140 8.5E-01 0.0278 5.7E-01 Roseburia_hominis UniRef90_D4L240 Cluster: CDP-diacylglycerol--glycerol-3-phosphate 3-phosphatidyltransferase 0.12 -0.0011 8.0E-01 9.0E-01 0.0047 6.4E-01 0.0012 6.4E-01 0.0051 5.4E-01 0.0086 1.4E-01 Roseburia_hominis UniRef90_G2T4T7 Cluster: Mutator family transposase 0.19 -0.0047 8.0E-01 9.0E-01 -0.0327 4.2E-01 0.0113 3.0E-01 -0.0592 8.2E-02 -0.0114 6.2E-01 Roseburia_hominis UniRef90_D4KV26 Cluster: DNA-invertase hin 0.20 0.0043 8.0E-01 9.0E-01 -0.0575 1.3E-01 -0.0060 5.5E-01 -0.0161 6.1E-01 0.0185 3.9E-01 Roseburia_hominis UniRef90_C4ZFD9 Cluster: DNA-binding response regulator 0.15 0.0011 8.0E-01 9.0E-01 -0.0042 6.6E-01 -0.0009 7.2E-01 -0.0021 8.0E-01 0.0076 1.6E-01 Roseburia_hominis UniRef90_C9YMF3 Cluster: Addiction module toxin, RelE/StbE family 0.31 0.0097 8.1E-01 9.0E-01 -0.0092 9.2E-01 -0.0124 5.9E-01 -0.0630 4.1E-01 -0.0076 8.8E-01 Roseburia_hominis UniRef90_D4LXN8 Cluster: TnpX site-specific recombinase 0.20 0.0018 8.2E-01 9.0E-01 -0.0006 9.7E-01 -0.0050 3.1E-01 0.0111 4.3E-01 0.0103 3.3E-01 Roseburia_hominis UniRef90_G2T465 Cluster: GDP-mannose 4,6-dehydratase 0.11 0.0084 8.2E-01 9.1E-01 0.0804 3.4E-01 0.0458 3.7E-02 0.0872 2.1E-01 0.0115 8.1E-01 Roseburia_hominis UniRef90_C9YMF4 Cluster: Addiction module antitoxin, RelB/DinJ family 0.23 -0.0084 8.3E-01 9.1E-01 0.0824 3.5E-01 -0.0387 9.6E-02 -0.0587 4.3E-01 -0.0242 6.3E-01 Roseburia_hominis UniRef90_G2SX22 Cluster: Histidine phosphatase family protein 0.10 0.0087 8.4E-01 9.2E-01 -0.1073 2.5E-01 -0.0329 1.8E-01 -0.0868 2.8E-01 0.0280 6.0E-01 Roseburia_hominis UniRef90_D4L0P3 Cluster: Adenylosuccinate lyase 0.14 0.0066 8.4E-01 9.2E-01 -0.1206 9.2E-02 -0.0328 9.1E-02 -0.0939 1.2E-01 0.0096 8.2E-01 Roseburia_hominis UniRef90_C4ZGA3 Cluster: Beta-xylosidase 0.19 0.0025 8.4E-01 9.2E-01 0.0026 9.2E-01 -0.0134 7.1E-02 0.0009 9.7E-01 0.0143 3.7E-01 Roseburia_hominis UniRef90_G2T5B1 Cluster: Flagellar basal-body rod protein FlgG 0.14 0.0088 8.5E-01 9.2E-01 -0.0979 3.6E-01 -0.0078 7.7E-01 0.0485 5.9E-01 0.0298 6.1E-01 Roseburia_hominis UniRef90_G2T1X9 Cluster: Putative lipid kinase 0.12 0.0069 8.5E-01 9.2E-01 -0.0577 4.8E-01 -0.0042 8.5E-01 -0.0010 9.9E-01 0.0356 4.5E-01 Roseburia_hominis UniRef90_G2T5P4 Cluster: ATP synthase subunit alpha 0.10 0.0050 8.6E-01 9.2E-01 -0.0435 4.9E-01 -0.0062 7.2E-01 -0.0425 4.3E-01 -0.0065 8.6E-01 Roseburia_hominis UniRef90_A9KJG8 Cluster: 30S ribosomal protein S11 0.25 0.0107 8.6E-01 9.3E-01 -0.0154 9.1E-01 -0.0436 2.4E-01 0.0593 6.1E-01 0.1237 1.2E-01 Roseburia_hominis UniRef90_G2T2Y3 Cluster: 4-deoxy-L-threo-5-hexosulose-uronate ketol-isomerase 0.11 0.0055 8.9E-01 9.3E-01 -0.0959 2.7E-01 -0.0343 1.3E-01 -0.0898 2.2E-01 0.0029 9.5E-01 Roseburia_hominis UniRef90_G2SYL4 Cluster: Cyclic di-GMP phosphodiesterase response regulator RpfG 0.21 0.0025 8.9E-01 9.4E-01 0.0029 9.4E-01 -0.0080 4.5E-01 -0.0224 5.1E-01 0.0160 4.8E-01 Roseburia_hominis UniRef90_G2T444 Cluster: PDZ domain-containing protein 0.10 -0.0038 9.0E-01 9.4E-01 -0.0332 6.2E-01 -0.0046 7.9E-01 -0.0435 4.5E-01 0.0241 5.3E-01 Roseburia_hominis UniRef90_M4RA63 Cluster: Methyltransferase domain protein 0.12 -0.0006 9.1E-01 9.5E-01 -0.0091 4.1E-01 0.0016 5.9E-01 -0.0311 9.3E-04 0.0005 9.4E-01 60

Supplementary Data 4a Supplementary Data 4a. Association of DNA enzyme within TMAO-associated species with plasma TMAO levels, and intakes of choline and red meat. Full model was adjusted for age, BMI, physical activity, energy intake, smoking, cumulative dietary quality, antibiotics use, probiotics use, the Bristol Stool Chart, and/or fish intake (for non-fish dietary variables). Choline Choline Red meat Red meat Plasma TMAO Species Enzyme ID Enzyme Name Detection intake-FFQ intake-7DDR intake-FFQ intake-7DDR Rate Effect P FDR Effect P Effect P Effect P Effect P Alistipes shahii 1.1.1.37 malate dehydrogenase 0.77 0.00012 6.6E-03 1.0E-02 -0.00004 6.0E-01 -0.00002 7.4E-01 -0.00003 6.5E-01 -0.00005 2.5E-01 Alistipes shahii 1.11.1.15 peroxiredoxin 0.75 0.00016 2.6E-04 3.5E-03 -0.00004 6.0E-01 -0.00006 2.4E-01 -0.00001 9.2E-01 -0.00003 5.0E-01 Alistipes shahii 1.15.1.1 superoxide dismutase 0.76 0.00015 1.2E-03 4.5E-03 -0.00001 8.9E-01 0.00001 8.1E-01 -0.00004 5.9E-01 -0.00002 5.9E-01 Alistipes shahii 1.16.3.2 bacterial non-heme ferritin 0.73 0.00011 5.4E-03 9.0E-03 0.00005 5.4E-01 -0.00001 8.7E-01 0.00002 8.1E-01 -0.00002 6.7E-01 Alistipes shahii 1.2.7.3 2-oxoglutarate synthase 0.76 0.00014 3.1E-03 6.9E-03 -0.00003 7.2E-01 0.00000 9.5E-01 -0.00007 3.5E-01 -0.00007 1.4E-01 Alistipes shahii 1.6.5.11 nadh dehydrogenase (quinone) 0.78 0.00023 2.1E-03 5.0E-03 0.00002 8.9E-01 -0.00003 7.6E-01 -0.00008 5.3E-01 -0.00003 6.6E-01 Alistipes shahii 1.6.5.3 nadh:ubiquinone reductase (h(+)-translocating) 0.77 0.00014 1.2E-03 4.5E-03 -0.00002 7.7E-01 0.00000 9.5E-01 -0.00002 8.3E-01 -0.00002 5.8E-01 Alistipes shahii 1.6.5.8 nadh:ubiquinone reductase (na(+)-transporting) 0.78 0.00018 1.7E-03 5.0E-03 -0.00003 7.8E-01 -0.00002 7.8E-01 -0.00004 7.2E-01 -0.00008 2.0E-01 Alistipes shahii 1.97.1.4 [formate-c-acetyltransferase]-activating enzyme 0.74 0.00012 1.9E-03 5.0E-03 -0.00007 3.6E-01 -0.00004 3.9E-01 -0.00004 4.8E-01 -0.00004 3.7E-01 Alistipes shahii 2.1.1.37 dna (cytosine-5-)-methyltransferase 0.47 0.00001 6.6E-01 6.9E-01 0.00004 5.8E-01 -0.00003 4.9E-01 0.00004 4.4E-01 -0.00001 7.4E-01 Alistipes shahii 2.2.1.6 acetolactate synthase 0.77 0.00012 3.5E-03 7.1E-03 -0.00005 5.2E-01 0.00004 4.5E-01 -0.00004 5.6E-01 -0.00001 8.5E-01 Alistipes shahii 2.3.1.79 maltose o-acetyltransferase 0.74 0.00012 2.0E-03 5.0E-03 0.00000 9.9E-01 0.00003 5.8E-01 0.00000 9.8E-01 -0.00004 3.9E-01 Alistipes shahii 2.4.99.17 s-adenosylmethionine:trna ribosyltransferase-isomerase 0.77 0.00013 9.0E-04 4.5E-03 -0.00002 8.4E-01 -0.00002 7.3E-01 -0.00002 7.5E-01 -0.00004 3.5E-01 Alistipes shahii 2.7.13.3 histidine kinase 0.77 0.00014 6.6E-04 4.5E-03 -0.00006 4.1E-01 0.00000 9.3E-01 -0.00007 3.0E-01 -0.00002 6.0E-01 Alistipes shahii 2.7.7.6 dna-directed rna polymerase 0.77 0.00013 8.5E-04 4.5E-03 0.00001 9.4E-01 -0.00002 6.2E-01 -0.00001 8.4E-01 -0.00005 2.0E-01 Alistipes shahii 2.7.7.7 dna-directed dna polymerase 0.78 0.00013 1.7E-02 2.2E-02 -0.00007 5.1E-01 -0.00002 7.3E-01 -0.00004 6.4E-01 -0.00008 1.4E-01 Alistipes shahii 3.1.3.5 5'-nucleotidase 0.77 0.00012 8.1E-04 4.5E-03 -0.00003 7.2E-01 0.00004 3.9E-01 0.00001 8.6E-01 -0.00003 3.6E-01 Alistipes shahii 3.1.4.46 glycerophosphodiester phosphodiesterase 0.76 0.00011 4.4E-03 7.7E-03 -0.00001 9.2E-01 -0.00002 7.5E-01 0.00001 8.2E-01 -0.00003 4.3E-01 Alistipes shahii 3.2.1.21 beta-glucosidase 0.78 0.00013 3.9E-03 7.1E-03 -0.00004 6.5E-01 -0.00004 5.0E-01 -0.00004 5.5E-01 -0.00001 7.7E-01 Alistipes shahii 3.4.13.3 transferred entry: 3.4.13.18 and 3.4.13.20 0.77 0.00011 2.1E-03 5.0E-03 -0.00003 6.4E-01 0.00000 9.7E-01 -0.00001 8.2E-01 -0.00003 4.6E-01 Alistipes shahii 3.4.21.102 c-terminal processing peptidase 0.78 0.00015 1.2E-03 4.5E-03 -0.00002 8.0E-01 0.00002 7.4E-01 -0.00003 7.2E-01 -0.00006 2.1E-01 Alistipes shahii 3.5.1.88 peptide deformylase 0.76 0.00010 2.0E-02 2.5E-02 -0.00004 5.8E-01 -0.00005 3.0E-01 0.00000 9.6E-01 -0.00003 4.7E-01 Alistipes shahii 3.6.4.12 dna helicase 0.78 0.00015 4.0E-03 7.2E-03 0.00002 8.4E-01 0.00002 7.7E-01 -0.00001 8.7E-01 -0.00008 1.5E-01 Alistipes shahii 4.1.1.41 methylmalonyl-coa decarboxylase 0.77 0.00011 1.2E-02 1.7E-02 0.00003 7.0E-01 0.00003 5.9E-01 -0.00001 8.9E-01 -0.00002 6.8E-01 Alistipes shahii 4.1.2.13 fructose-bisphosphate aldolase 0.77 0.00016 2.5E-04 3.5E-03 -0.00002 8.0E-01 0.00002 6.3E-01 -0.00006 4.3E-01 -0.00006 1.4E-01 Alistipes shahii 4.2.1.33 3-isopropylmalate dehydratase 0.77 0.00010 1.5E-02 2.0E-02 -0.00006 4.0E-01 -0.00002 6.5E-01 -0.00003 6.1E-01 -0.00001 8.7E-01 Alistipes shahii 4.2.1.46 dtdp-glucose 4,6-dehydratase 0.77 0.00014 3.1E-03 6.9E-03 -0.00007 4.1E-01 0.00001 8.2E-01 -0.00003 6.8E-01 -0.00007 1.4E-01 Alistipes shahii 5.2.1.8 peptidylprolyl Isomerase 0.78 0.00018 8.9E-03 1.3E-02 -0.00001 9.3E-01 0.00002 8.1E-01 -0.00003 8.0E-01 -0.00008 2.5E-01 Alistipes shahii 5.99.1.2 dna topoisomerase 0.76 0.00000 9.8E-01 9.9E-01 -0.00002 7.4E-01 -0.00001 7.6E-01 -0.00009 1.0E-01 0.00001 7.3E-01 Alistipes shahii 5.99.1.3 dna topoisomerase (atp-hydrolyzing) 0.78 0.00013 1.6E-03 5.0E-03 -0.00001 8.9E-01 0.00002 6.6E-01 -0.00001 8.8E-01 -0.00003 4.8E-01 Alistipes shahii 6.2.1.3 long-chain-fatty-acid--coa ligase 0.78 0.00012 2.1E-03 5.0E-03 -0.00002 7.4E-01 0.00003 5.5E-01 -0.00002 8.1E-01 -0.00006 1.6E-01 Alistipes shahii 6.3.2.9 udp-n-acetylmuramoyl-l-alanine--d-glutamate ligase 0.76 0.00016 1.1E-03 4.5E-03 -0.00007 4.7E-01 -0.00006 3.4E-01 -0.00002 7.9E-01 -0.00008 1.3E-01 Alistipes shahii 6.3.5.1 nad(+) synthase (glutamine-hydrolyzing) 0.78 0.00010 1.4E-02 1.9E-02 -0.00002 8.1E-01 0.00000 9.4E-01 -0.00005 4.8E-01 -0.00004 3.5E-01 Alistipes shahii ungrouped no_name 0.78 0.00346 1.8E-03 5.0E-03 -0.00049 8.2E-01 -0.00002 9.9E-01 -0.00147 4.3E-01 -0.00056 6.2E-01 Clostridiales bacterium 1 7 47Fungrouped no_name 0.19 0.00176 3.5E-03 7.1E-03 -0.00060 5.6E-01 0.00048 5.0E-01 0.00045 6.0E-01 0.00050 4.1E-01 Clostridium citroniae ungrouped no_name 0.16 0.00091 6.8E-02 7.7E-02 -0.00017 8.4E-01 -0.00027 6.5E-01 -0.00139 4.8E-02 -0.00057 2.6E-01 Clostridium clostridioforme ungrouped no_name 0.11 0.00299 2.5E-04 3.5E-03 0.00010 9.5E-01 0.00008 9.3E-01 0.00130 3.3E-01 -0.00002 9.8E-01 Clostridium nexile ungrouped no_name 0.14 -0.00259 1.2E-02 1.7E-02 0.00041 8.3E-01 -0.00053 6.6E-01 0.00119 4.6E-01 -0.00069 5.1E-01 Erysipelotrichaceae bacteriumungrouped no_name 0.12 0.00075 4.8E-02 5.8E-02 0.00008 9.1E-01 -0.00009 8.3E-01 0.00011 8.3E-01 -0.00053 1.7E-01 Eubacterium biforme 2.7.1.69 protein-n(pi)-phosphohistidine--sugar phosphotransferase 0.24 -0.00023 4.4E-04 4.5E-03 -0.00004 7.6E-01 -0.00003 6.8E-01 -0.00010 3.8E-01 0.00014 3.1E-02 Eubacterium biforme 2.7.7.6 dna-directed rna polymerase 0.24 -0.00015 3.5E-03 7.1E-03 -0.00003 7.7E-01 -0.00003 6.0E-01 -0.00010 2.9E-01 0.00012 2.0E-02 Eubacterium biforme 2.7.7.7 dna-directed dna polymerase 0.24 -0.00011 7.7E-03 1.1E-02 0.00000 9.6E-01 -0.00001 7.7E-01 -0.00008 3.0E-01 0.00012 3.9E-03 Eubacterium biforme 3.6.3.14 h(+)-transporting two-sector atpase 0.24 -0.00016 5.2E-03 8.8E-03 -0.00002 8.8E-01 -0.00002 7.4E-01 -0.00010 3.1E-01 0.00015 8.6E-03 Eubacterium biforme ungrouped no_name 0.24 -0.00252 3.8E-03 7.1E-03 -0.00016 9.2E-01 -0.00079 4.4E-01 -0.00183 2.3E-01 0.00202 2.0E-02 Eubacterium hallii 1.1.1.100 3-oxoacyl-[acyl-carrier-protein] reductase 0.88 0.00008 5.1E-02 5.9E-02 -0.00001 9.4E-01 0.00006 2.1E-01 0.00004 5.3E-01 -0.00004 3.9E-01 Eubacterium hallii 1.1.1.159 7-alpha-hydroxysteroid dehydrogenase 0.88 0.00008 5.1E-02 5.9E-02 -0.00001 9.4E-01 0.00006 2.1E-01 0.00004 5.3E-01 -0.00004 3.9E-01 Eubacterium hallii 1.1.1.25 shikimate dehydrogenase 0.91 0.00018 5.9E-04 4.5E-03 0.00008 3.6E-01 0.00003 6.6E-01 0.00002 7.4E-01 -0.00004 4.7E-01 Eubacterium hallii 2.2.1.2 transaldolase 0.87 0.00013 3.7E-03 7.1E-03 0.00009 2.3E-01 0.00004 4.7E-01 0.00001 8.8E-01 -0.00002 7.1E-01 Eubacterium hallii 2.7.13.3 histidine kinase 0.92 0.00011 3.6E-02 4.5E-02 0.00001 9.4E-01 0.00003 6.4E-01 -0.00003 7.2E-01 -0.00004 5.0E-01 Eubacterium hallii 2.7.7.4 sulfate adenylyltransferase 0.91 0.00016 6.3E-04 4.5E-03 0.00008 2.9E-01 0.00003 5.9E-01 0.00004 5.7E-01 -0.00002 6.4E-01

Supplementary Data 4a Choline Choline Red meat Red meat Plasma TMAO Species Enzyme ID Enzyme Name Detection intake-FFQ intake-7DDR intake-FFQ intake-7DDR Rate Effect P FDR Effect P Effect P Effect P Effect P Eubacterium hallii 2.7.7.7 dna-directed dna polymerase 0.92 0.00006 3.0E-01 3.2E-01 -0.00008 4.5E-01 -0.00002 7.8E-01 -0.00007 4.7E-01 -0.00006 3.1E-01 Eubacterium hallii 2.7.8.5 cdp-diacylglycerol--glycerol-3-phosphate 3-phosphatidyltransferase 0.92 0.00000 9.9E-01 9.9E-01 -0.00002 8.3E-01 0.00002 7.2E-01 0.00001 8.8E-01 -0.00002 6.1E-01 Eubacterium hallii 3.4.21.89 signal peptidase I 0.81 0.00013 1.8E-02 2.3E-02 0.00006 5.0E-01 0.00005 4.8E-01 0.00004 6.4E-01 -0.00007 2.2E-01 Eubacterium hallii 3.5.1.24 choloylglycine hydrolase 0.92 0.00000 9.8E-01 9.9E-01 -0.00005 5.2E-01 0.00002 7.5E-01 0.00010 1.3E-01 -0.00006 1.7E-01 Eubacterium hallii 3.6.3.14 h(+)-transporting two-sector atpase 0.92 0.00024 1.2E-04 3.5E-03 0.00010 3.4E-01 0.00007 3.2E-01 0.00005 5.3E-01 -0.00006 3.7E-01 Eubacterium hallii 3.6.4.12 dna helicase 0.91 0.00016 5.9E-03 9.6E-03 0.00014 1.9E-01 0.00002 7.5E-01 0.00005 5.7E-01 -0.00006 2.9E-01 Eubacterium hallii 5.2.1.8 peptidylprolyl Isomerase 0.9 0.00017 1.6E-04 3.5E-03 0.00011 1.7E-01 0.00002 6.6E-01 0.00002 8.0E-01 -0.00005 3.2E-01 Eubacterium hallii ungrouped no_name 0.92 0.00405 7.8E-04 4.5E-03 0.00243 2.5E-01 0.00077 5.9E-01 0.00115 5.0E-01 -0.00088 4.7E-01 Roseburia hominis 2.1.1.72 site-specific dna-methyltransferase (adenine-specific) 0.83 0.00002 6.6E-01 6.9E-01 0.00008 3.2E-01 -0.00005 3.3E-01 0.00007 3.1E-01 -0.00001 8.3E-01 Roseburia hominis 2.7.13.3 histidine kinase 0.87 0.00013 1.4E-03 4.7E-03 0.00002 8.2E-01 -0.00008 7.9E-02 0.00006 3.1E-01 -0.00005 2.3E-01 Roseburia hominis 2.7.8.5 cdp-diacylglycerol--glycerol-3-phosphate 3-phosphatidyltransferase 0.87 0.00009 5.3E-02 6.1E-02 -0.00001 8.7E-01 -0.00002 7.2E-01 0.00006 3.5E-01 -0.00001 8.6E-01 Roseburia hominis 3.2.1.23 beta-galactosidase 0.87 0.00008 4.0E-02 4.9E-02 0.00002 7.3E-01 -0.00004 4.0E-01 0.00006 3.1E-01 -0.00001 8.9E-01 Roseburia hominis 3.6.3.14 h(+)-transporting two-sector atpase 0.86 0.00016 1.8E-03 5.0E-03 -0.00002 8.4E-01 -0.00005 4.3E-01 0.00000 9.5E-01 -0.00005 3.8E-01 Roseburia hominis 3.6.4.12 dna helicase 0.87 0.00020 9.8E-04 4.5E-03 -0.00003 7.7E-01 -0.00007 3.6E-01 0.00003 7.1E-01 -0.00003 5.7E-01 Roseburia hominis 4.2.3.3 methylglyoxal synthase 0.73 0.00009 2.4E-01 2.6E-01 -0.00013 3.2E-01 -0.00016 8.2E-02 -0.00009 4.1E-01 -0.00016 4.3E-02 Roseburia hominis ungrouped no_name 0.87 0.00338 7.6E-03 1.1E-02 0.00034 8.8E-01 -0.00159 2.9E-01 0.00123 5.1E-01 -0.00112 3.8E-01

Supplementary Data 4b Supplementary Data 4b. Association of transcriptions of enzymes (RNA/DNA ratio) within TMAO-associated species with plasma TMAO levels, and intakes of choline and red meat. Full model was adjusted for age, BMI, physical activity, energy intake, smoking, cumulative dietary quality (since 1986), antibiotics use, probiotics use, the Bristol Stool Chart, and/or fish intake (for non-fish dietary variables). Enzyme Detectio Plasma TMAO Choline Choline Red meat Red meat Species Enzyme Name ID n Rate Effect P FDR Effect P Effect P Effect P Effect P alistipes_shahii 1.15.1.1 superoxide dismutase 0.38 0.0360 4.5E-01 5.9E-01 0.1295 1.5E-01 -0.0765 2.0E-01 0.0704 5.2E-01 -0.0330 2.3E-01 alistipes_shahii 2.7.1.45 2-dehydro-3-deoxygluconokinase 0.31 0.0051 8.9E-01 9.1E-01 0.0483 4.7E-01 -0.0502 2.6E-01 0.1379 7.8E-02 -0.0082 6.9E-01 alistipes_shahii 3.2.2.27 uracil-dna glycosylase 0.21 -0.0359 1.0E-01 3.2E-01 0.0035 9.3E-01 0.0323 2.4E-01 0.0571 2.4E-01 -0.0095 4.6E-01 alistipes_shahii 2.4.2.3 uridine phosphorylase 0.38 0.0633 1.8E-01 3.8E-01 0.0842 3.5E-01 -0.0118 8.4E-01 0.1013 3.5E-01 -0.0174 5.3E-01 alistipes_shahii 2.1.1.193 16s rrna (uracil(1498)-n(3))- 0.16 0.0274 1.6E-01 3.6E-01 0.0369 3.0E-01 -0.0430 8.4E-02 0.0262 5.5E-01 -0.0205 7.5E-02 methyltransferase alistipes_shahii 4.1.99.2 tyrosine phenol-lyase 0.38 0.0497 3.4E-01 5.0E-01 -0.0108 9.1E-01 -0.0096 8.8E-01 -0.0491 6.8E-01 -0.0103 7.3E-01 alistipes_shahii 5.3.1.17 5-dehydro-4-deoxy-d-glucuronate 0.34 0.0386 4.2E-01 5.6E-01 0.0966 2.8E-01 -0.0943 1.1E-01 0.0570 5.9E-01 -0.0326 2.3E-01 alistipes_shahii 1.1.1.25 shikimateIsomerase dehydrogenase 0.33 0.0449 2.9E-01 4.6E-01 0.0434 5.9E-01 0.0336 5.3E-01 0.1275 1.8E-01 0.0200 4.2E-01 alistipes_shahii 2.7.7.24 glucose-1-phosphate 0.23 0.0190 3.7E-01 5.3E-01 0.0711 7.2E-02 0.0452 1.0E-01 0.0428 3.6E-01 -0.0079 5.4E-01 alistipes_shahii 2.4.1.11 glycogen(starch)thymidylyltransferase synthase 0.43 0.0395 1.7E-01 3.7E-01 0.0634 2.4E-01 -0.0673 6.2E-02 0.0739 2.5E-01 -0.0045 7.9E-01 alistipes_shahii 2.1.1.163 demethylmenaquinone 0.16 0.0148 4.8E-01 6.1E-01 0.0343 3.6E-01 -0.0278 2.9E-01 0.0915 4.7E-02 -0.0165 1.7E-01 alistipes_shahii 2.3.1.179 beta-ketoacyl-[acyl-carrier-protein]methyltransferase 0.48 0.0543 3.8E-01 5.3E-01 0.0880 4.5E-01 -0.0256 7.4E-01 -0.0224 8.7E-01 -0.0226 5.3E-01 synthase II alistipes_shahii 1.3.5.1 succinate dehydrogenase (quinone) 0.49 0.0858 9.3E-02 3.1E-01 0.1502 1.2E-01 -0.0364 5.7E-01 -0.0274 8.1E-01 -0.0385 1.9E-01 alistipes_shahii 3.2.1.20 alpha-glucosidase 0.1 -0.0272 7.8E-02 2.9E-01 0.0168 5.6E-01 -0.0224 2.4E-01 0.0280 4.2E-01 0.0032 7.2E-01 alistipes_shahii 5.2.1.8 peptidylprolyl Isomerase 0.44 0.0399 2.7E-01 4.4E-01 0.0741 2.8E-01 -0.0365 4.2E-01 0.0841 3.0E-01 -0.0024 9.1E-01 alistipes_shahii 2.7.1.2 glucokinase 0.43 0.0594 2.4E-01 4.3E-01 0.1457 1.2E-01 -0.0302 6.3E-01 0.0181 8.7E-01 -0.0305 2.9E-01 alistipes_shahii 2.3.1.181 lipoyl(octanoyl) transferase 0.33 0.0348 3.3E-01 5.0E-01 0.1118 9.6E-02 -0.0115 8.0E-01 0.1030 2.0E-01 -0.0156 4.5E-01 alistipes_shahii 5.4.2.11 phosphoglycerate mutase (2,3- 0.37 0.0892 1.3E-01 3.3E-01 0.0726 4.9E-01 -0.0736 3.1E-01 -0.1348 3.1E-01 -0.0352 3.0E-01 diphosphoglycerate-dependent) alistipes_shahii 1.8.1.4 dihydrolipoyl dehydrogenase 0.39 0.0321 5.3E-01 6.5E-01 0.1664 8.1E-02 0.0192 7.6E-01 0.0411 7.2E-01 -0.0062 8.3E-01 alistipes_shahii 4.1.1.41 methylmalonyl-coa decarboxylase 0.51 0.0891 6.2E-02 2.7E-01 0.0797 3.8E-01 -0.0526 3.7E-01 -0.0201 8.5E-01 -0.0300 2.7E-01 alistipes_shahii 2.8.4.4 [ribosomal protein s12] (aspartate(89)- 0.35 0.0796 4.2E-02 2.5E-01 0.0022 9.8E-01 -0.0079 8.7E-01 0.0779 4.0E-01 -0.0036 8.7E-01 c(3))-methylthiotransferase alistipes_shahii 2.7.1.40 pyruvate kinase 0.38 0.0347 3.8E-01 5.3E-01 0.1019 1.6E-01 -0.0741 1.3E-01 0.0577 5.1E-01 -0.0123 5.9E-01 alistipes_shahii 2.4.1.227 acetylglucosaminyltransferase 0.34 0.0590 1.3E-01 3.3E-01 0.1284 8.1E-02 -0.0240 6.2E-01 0.1453 1.0E-01 0.0397 8.0E-02 alistipes_shahii 4.3.1.4 formimidoyltetrahydrofolate 0.34 0.0609 1.9E-01 3.8E-01 0.0668 4.4E-01 -0.0581 3.1E-01 0.0748 4.7E-01 0.0010 9.7E-01 cyclodeaminase alistipes_shahii 2.5.1.47 cysteine synthase 0.24 0.0678 1.2E-02 1.8E-01 0.0913 7.1E-02 0.0059 8.6E-01 0.0326 5.9E-01 -0.0191 2.3E-01 alistipes_shahii 2.7.2.7 butyrate kinase 0.27 0.0598 4.6E-02 2.6E-01 0.0947 9.6E-02 0.0230 5.4E-01 -0.0547 4.3E-01 -0.0021 9.1E-01 alistipes_shahii 4.1.1.49 phosphoenolpyruvate carboxykinase 0.51 0.0889 1.2E-01 3.3E-01 0.1312 2.2E-01 -0.0609 3.8E-01 -0.0112 9.3E-01 -0.0620 5.6E-02 alistipes_shahii 3.1.1.29 aminoacyl-trna(atp) hydrolase 0.23 0.0292 2.4E-01 4.3E-01 0.0426 3.6E-01 -0.0396 2.0E-01 0.0286 6.0E-01 -0.0069 6.3E-01 alistipes_shahii 1.1.1.193 5-amino-6-(5- 0.25 0.0136 6.8E-01 7.6E-01 -0.0316 6.0E-01 -0.0072 8.6E-01 0.0946 1.9E-01 -0.0049 8.0E-01 phosphoribosylamino)uracil reductase alistipes_shahii 2.7.4.8 guanylate kinase 0.17 0.0081 7.4E-01 8.1E-01 0.0246 6.1E-01 -0.0154 6.3E-01 0.0705 2.2E-01 -0.0122 4.1E-01 alistipes_shahii 1.1.1.23 histidinol dehydrogenase 0.12 0.0032 8.5E-01 8.9E-01 0.0142 6.3E-01 0.0072 7.3E-01 0.0440 2.4E-01 -0.0124 2.1E-01 alistipes_shahii 3.5.4.16 gtp cyclohydrolase I 0.13 -0.0380 1.9E-01 3.8E-01 0.0027 9.6E-01 0.0191 5.9E-01 0.1271 4.3E-02 -0.0056 7.4E-01 alistipes_shahii 1.1.1.37 malate dehydrogenase 0.52 0.0743 2.0E-01 4.0E-01 0.1098 3.2E-01 -0.0717 3.2E-01 0.0175 9.0E-01 -0.0302 3.7E-01 alistipes_shahii 2.1.1.228 trna (guanine(37)-n(1))- 0.24 0.0123 6.0E-01 7.1E-01 0.0517 2.3E-01 0.0131 6.5E-01 -0.0364 5.0E-01 -0.0238 7.9E-02 alistipes_shahii 5.99.1.2 dnamethyltransferase topoisomerase 0.1 0.0126 2.7E-01 4.4E-01 0.0221 2.7E-01 0.0087 5.4E-01 0.0084 7.4E-01 0.0064 3.3E-01 alistipes_shahii 3.1.3.45 3-deoxy-manno-octulosonate-8- 0.32 0.0223 5.9E-01 7.0E-01 0.0993 1.9E-01 -0.0424 4.1E-01 0.0377 6.8E-01 0.0013 9.6E-01 phosphatase alistipes_shahii 1.1.1.267 1-deoxy-d-xylulose-5-phosphate 0.33 0.0448 2.6E-01 4.4E-01 -0.0363 6.3E-01 -0.0227 6.4E-01 0.0440 6.3E-01 -0.0110 6.3E-01 reductoisomerase alistipes_shahii 3.1.26.4 ribonuclease h 0.26 0.0560 1.2E-01 3.3E-01 0.0202 7.6E-01 -0.0340 4.5E-01 0.0464 5.7E-01 -0.0043 8.4E-01 alistipes_shahii 3.6.5.n1 elongation factor 4 0.35 0.0287 2.9E-01 4.6E-01 0.0194 7.0E-01 -0.0402 2.4E-01 -0.0173 7.8E-01 -0.0272 8.5E-02 alistipes_shahii 3.4.21.92 endopeptidase clp 0.31 0.0399 2.5E-01 4.3E-01 0.0501 4.3E-01 -0.0097 8.2E-01 -0.0243 7.5E-01 -0.0279 1.6E-01 alistipes_shahii 2.4.2.8 hypoxanthine 0.24 -0.0070 8.2E-01 8.7E-01 0.0696 2.3E-01 0.0005 9.9E-01 0.0039 9.6E-01 -0.0239 1.8E-01 alistipes_shahii 2.1.3.9 n-acetylornithinephosphoribosyltransferase 0.42 0.0810 1.2E-01 3.3E-01 0.0748 4.4E-01 -0.0298 6.5E-01 0.0066 9.6E-01 0.0018 9.5E-01 alistipes_shahii 2.7.1.4 fructokinasecarbamoyltransferase 0.3 0.0497 2.7E-01 4.4E-01 0.0327 6.9E-01 0.0055 9.2E-01 0.0024 9.8E-01 -0.0211 4.1E-01 alistipes_shahii 4.2.1.8 mannonate dehydratase 0.27 0.0698 3.0E-02 2.2E-01 0.0597 3.3E-01 -0.0003 9.9E-01 0.0725 3.1E-01 0.0068 7.2E-01 alistipes_shahii 5.4.99.5 chorismate mutase 0.21 0.0363 1.3E-01 3.3E-01 0.0420 3.4E-01 -0.0063 8.3E-01 0.0691 1.9E-01 -0.0113 4.1E-01 alistipes_shahii 3.2.2.20 dna-3-methyladenine glycosylase I 0.17 0.0454 7.1E-02 2.8E-01 0.0072 8.7E-01 -0.0650 3.7E-02 -0.0582 3.1E-01 -0.0180 2.2E-01 alistipes_shahii 2.7.13.3 histidine kinase 0.38 0.0424 1.3E-01 3.3E-01 0.0531 3.1E-01 -0.0219 5.4E-01 0.0815 1.9E-01 -0.0233 1.6E-01 alistipes_shahii 2.2.1.1 transketolase 0.47 0.0388 4.0E-01 5.5E-01 0.1171 1.7E-01 -0.0776 1.7E-01 -0.0323 7.5E-01 -0.0246 3.5E-01 alistipes_shahii 2.5.1.15 dihydropteroate synthase 0.21 0.0326 2.6E-01 4.4E-01 0.0164 7.5E-01 -0.0435 2.2E-01 -0.0901 1.7E-01 -0.0277 9.6E-02 alistipes_shahii 3.5.4.28 s-adenosylhomocysteine deaminase 0.29 0.0597 5.8E-02 2.7E-01 0.0147 8.0E-01 -0.0579 1.4E-01 0.0473 5.0E-01 -0.0190 3.0E-01 alistipes_shahii 6.3.5.5 carbamoyl-phosphate synthase 0.26 0.0496 3.4E-02 2.4E-01 0.0310 4.8E-01 -0.0243 4.1E-01 -0.0359 4.9E-01 -0.0201 1.4E-01 (glutamine-hydrolyzing) alistipes_shahii 2.7.7.41 phosphatidate cytidylyltransferase 0.26 -0.0159 6.1E-01 7.2E-01 0.0186 7.5E-01 -0.0006 9.9E-01 0.0182 7.9E-01 0.0004 9.8E-01 alistipes_shahii 3.4.13.21 dipeptidase e 0.28 -0.0045 9.0E-01 9.2E-01 0.0315 6.2E-01 -0.0046 9.2E-01 -0.0119 8.7E-01 -0.0018 9.3E-01 alistipes_shahii 4.2.1.11 phosphopyruvate hydratase 0.44 0.0685 2.4E-01 4.3E-01 0.1176 2.8E-01 -0.0171 8.1E-01 0.0503 7.0E-01 -0.0488 1.4E-01 alistipes_shahii 4.2.99.18 dna-(apurinic or apyrimidinic site) 0.13 0.0196 3.2E-01 4.8E-01 0.0708 4.7E-02 -0.0282 2.6E-01 0.0174 6.9E-01 0.0001 1.0E+00 lyase alistipes_shahii 2.1.1.34 trna (guanosine(18)-2'-o)- 0.28 0.0136 7.0E-01 7.7E-01 0.1117 8.3E-02 -0.0577 1.9E-01 0.0704 3.7E-01 -0.0017 9.3E-01 methyltransferase alistipes_shahii 3.4.11.18 methionyl aminopeptidase 0.44 0.0669 2.6E-01 4.4E-01 0.1446 2.0E-01 -0.1026 1.6E-01 0.0823 5.4E-01 -0.0488 1.5E-01

Supplementary Data 4b Enzyme Detectio Plasma TMAO Choline Choline Red meat Red meat Species Enzyme Name ID n Rate Effect P FDR Effect P Effect P Effect P Effect P alistipes_shahii 2.7.2.1 acetate kinase 0.35 0.0371 3.5E-01 5.1E-01 -0.0399 6.0E-01 -0.0042 9.3E-01 0.0733 4.1E-01 -0.0140 5.4E-01 alistipes_shahii 2.1.1.72 site-specific dna-methyltransferase 0.19 0.0075 7.0E-01 7.7E-01 0.0303 4.1E-01 0.0029 9.1E-01 0.0550 2.0E-01 0.0092 4.3E-01 (adenine-specific) alistipes_shahii 6.1.1.3 threonine--trna ligase 0.43 0.0704 5.4E-02 2.6E-01 0.0919 1.8E-01 -0.0149 7.5E-01 0.0511 5.4E-01 -0.0288 1.7E-01 alistipes_shahii 3.1.3.25 Inositol-phosphate phosphatase 0.34 0.0574 1.7E-01 3.6E-01 0.0493 5.2E-01 -0.0652 2.1E-01 0.0863 3.5E-01 -0.0058 8.1E-01 alistipes_shahii 6.3.4.4 adenylosuccinate synthase 0.39 0.0434 3.0E-01 4.6E-01 0.0472 5.5E-01 0.0221 6.7E-01 0.0012 9.9E-01 -0.0211 3.8E-01 alistipes_shahii 2.3.1.79 maltose o-acetyltransferase 0.28 0.0583 5.4E-02 2.6E-01 0.0138 8.0E-01 -0.0135 7.2E-01 0.0687 3.0E-01 -0.0207 2.4E-01 alistipes_shahii 4.2.3.3 methylglyoxal synthase 0.26 0.0443 2.6E-01 4.4E-01 0.0050 9.4E-01 -0.0814 9.7E-02 -0.0105 9.0E-01 -0.0572 1.2E-02 alistipes_shahii 2.7.4.9 dtmp kinase 0.25 -0.0059 8.5E-01 8.9E-01 0.0355 5.4E-01 -0.0015 9.7E-01 0.0513 4.6E-01 -0.0175 3.4E-01 alistipes_shahii 2.1.1.199 16s rrna (cytosine(1402)-n(4))- 0.32 0.0659 8.4E-02 2.9E-01 0.1032 1.5E-01 -0.0172 7.1E-01 0.0468 5.9E-01 0.0130 5.5E-01 methyltransferase alistipes_shahii 4.2.1.126 n-acetylmuramic acid 6-phosphate 0.33 0.0073 8.7E-01 9.0E-01 -0.0034 9.7E-01 -0.0255 6.4E-01 -0.0092 9.2E-01 -0.0103 6.8E-01 etherase alistipes_shahii 2.1.1.223 trna(1)(val) (adenine(37)-n(6))- 0.15 0.0167 4.7E-01 6.1E-01 0.0137 7.3E-01 -0.0034 9.1E-01 0.0259 6.1E-01 0.0088 5.1E-01 methyltransferase alistipes_shahii 3.1.1.11 pectinesterase 0.18 0.0274 1.5E-01 3.5E-01 0.0235 5.1E-01 0.0444 6.7E-02 0.0199 6.3E-01 -0.0040 7.2E-01 alistipes_shahii 4.2.1.7 altronate dehydratase 0.31 0.0348 2.9E-01 4.5E-01 0.0863 1.6E-01 -0.0346 3.9E-01 0.0566 4.3E-01 -0.0205 2.8E-01 alistipes_shahii 2.4.1.21 starch synthase 0.42 0.0368 5.3E-01 6.5E-01 0.0984 3.7E-01 0.0801 2.7E-01 0.0575 6.7E-01 -0.0042 9.0E-01 alistipes_shahii 1.3.1.98 udp-n-acetylmuramate dehydrogenase 0.28 0.0211 4.6E-01 5.9E-01 0.0584 2.7E-01 -0.0067 8.5E-01 -0.0519 4.1E-01 -0.0339 3.9E-02

alistipes_shahii 1.1.1.58 tagaturonate reductase 0.26 0.0122 6.3E-01 7.3E-01 0.0107 8.2E-01 -0.0486 1.2E-01 0.0220 6.9E-01 -0.0090 5.4E-01 alistipes_shahii 2.7.7.18 nicotinate-nucleotide 0.18 0.0176 4.0E-01 5.5E-01 0.0083 8.3E-01 -0.0236 3.7E-01 0.0522 2.5E-01 0.0041 7.4E-01 adenylyltransferase alistipes_shahii 3.2.1.21 beta-glucosidase 0.44 0.0028 9.2E-01 9.3E-01 0.0386 4.5E-01 -0.0181 5.9E-01 0.0214 7.3E-01 -0.0281 7.2E-02 alistipes_shahii 3.5.4.5 cytidine deaminase 0.35 0.0320 5.3E-01 6.5E-01 0.1248 1.9E-01 -0.0579 3.6E-01 0.1620 1.6E-01 -0.0278 3.5E-01 alistipes_shahii 2.1.2.9 methionyl-trna formyltransferase 0.33 0.0662 1.1E-01 3.3E-01 0.0860 2.8E-01 -0.0147 7.8E-01 -0.0188 8.4E-01 -0.0230 3.5E-01 alistipes_shahii 2.1.3.3 ornithine carbamoyltransferase 0.42 0.0810 1.2E-01 3.3E-01 0.0748 4.4E-01 -0.0298 6.5E-01 0.0066 9.6E-01 0.0018 9.5E-01 alistipes_shahii 6.3.2.6 phosphoribosylaminoimidazolesuccino 0.31 0.0200 5.1E-01 6.4E-01 0.0262 6.4E-01 0.0034 9.3E-01 0.0267 6.9E-01 -0.0348 4.7E-02 carboxamide synthase alistipes_shahii 3.4.24.71 endothelin-converting enzyme 1 0.32 0.0352 1.3E-01 3.3E-01 0.0504 2.6E-01 -0.0070 8.1E-01 0.0399 4.5E-01 -0.0266 4.9E-02 alistipes_shahii 1.1.1.272 d-2-hydroxyacid dehydrogenase 0.21 0.0045 8.3E-01 8.8E-01 0.0546 1.5E-01 -0.0301 2.6E-01 -0.0084 8.5E-01 -0.0236 5.5E-02 (nadp(+)) alistipes_shahii 2.7.7.6 dna-directed rna polymerase 0.46 0.0932 8.4E-02 2.9E-01 0.0791 4.3E-01 -0.0670 3.2E-01 0.0874 4.7E-01 -0.0044 8.9E-01 alistipes_shahii 6.3.1.5 nad(+) synthase 0.3 0.0224 3.8E-01 5.3E-01 0.0657 1.7E-01 0.0083 8.0E-01 0.0148 8.0E-01 -0.0189 2.0E-01 alistipes_shahii 2.5.1.7 udp-n-acetylglucosamine 1- 0.34 0.0280 3.8E-01 5.3E-01 -0.0025 9.7E-01 -0.0319 4.2E-01 -0.0242 7.4E-01 -0.0236 2.0E-01 carboxyvinyltransferase alistipes_shahii 1.6.5.3 nadh:ubiquinone reductase (h(+)- 0.25 0.0143 4.3E-01 5.7E-01 0.0393 2.3E-01 -0.0197 3.8E-01 0.0472 2.2E-01 -0.0129 2.2E-01 translocating) alistipes_shahii 3.5.4.31 s-methyl-5'-thioadenosine deaminase 0.29 0.0597 5.8E-02 2.7E-01 0.0147 8.0E-01 -0.0579 1.4E-01 0.0473 5.0E-01 -0.0190 3.0E-01 alistipes_shahii 3.5.2.3 dihydroorotase 0.27 0.0294 3.1E-01 4.7E-01 0.0716 1.9E-01 -0.0014 9.7E-01 -0.0196 7.7E-01 -0.0047 7.9E-01 alistipes_shahii 2.3.1.57 diamine n-acetyltransferase 0.28 0.0095 8.0E-01 8.5E-01 0.0876 2.0E-01 -0.0049 9.2E-01 -0.0669 4.2E-01 -0.0196 3.7E-01 alistipes_shahii 2.4.2.19 nicotinate-nucleotide diphosphorylase 0.25 0.0249 4.5E-01 5.9E-01 0.1246 4.2E-02 -0.0261 5.3E-01 0.0355 6.3E-01 -0.0119 5.4E-01 (carboxylating) alistipes_shahii 3.5.1.32 hippurate hydrolase 0.24 0.0127 6.7E-01 7.6E-01 -0.0156 7.8E-01 -0.0177 6.3E-01 -0.0588 3.8E-01 -0.0175 3.0E-01 alistipes_shahii 5.3.1.1 triose-phosphate Isomerase 0.42 0.0711 1.7E-01 3.7E-01 0.0503 6.1E-01 -0.0136 8.3E-01 0.1341 2.5E-01 -0.0024 9.4E-01 alistipes_shahii 2.1.1.177 23s rrna (pseudouridine(1915)-n(3))- 0.19 0.0586 7.0E-02 2.8E-01 0.0921 1.3E-01 -0.0060 8.8E-01 0.0516 4.8E-01 -0.0144 4.4E-01 methyltransferase alistipes_shahii 3.1.3.41 4-nitrophenylphosphatase 0.26 0.0117 7.0E-01 7.7E-01 0.0107 8.5E-01 -0.0223 5.6E-01 0.0600 3.7E-01 0.0029 8.7E-01 alistipes_shahii 6.1.1.18 glutamine--trna ligase 0.33 0.0468 7.4E-02 2.8E-01 0.0401 4.2E-01 -0.0258 4.3E-01 0.0356 5.5E-01 -0.0287 5.9E-02 alistipes_shahii 4.2.1.10 3-dehydroquinate dehydratase 0.17 0.0318 2.6E-01 4.4E-01 0.0672 1.7E-01 -0.0109 7.6E-01 -0.0289 6.4E-01 0.0004 9.8E-01 alistipes_shahii 1.4.3.16 l-aspartate oxidase 0.29 0.0495 2.8E-02 2.2E-01 0.0135 7.5E-01 -0.0147 6.0E-01 0.0383 4.5E-01 -0.0190 1.5E-01 alistipes_shahii 4.2.3.1 threonine synthase 0.26 0.0492 7.9E-02 2.9E-01 0.0429 3.9E-01 0.0144 6.9E-01 0.0280 6.5E-01 0.0107 5.2E-01 alistipes_shahii 4.1.1.20 diaminopimelate decarboxylase 0.23 0.0203 3.7E-01 5.3E-01 0.0323 4.4E-01 -0.0428 1.4E-01 0.0051 9.2E-01 -0.0139 3.0E-01 alistipes_shahii 2.4.2.17 atp phosphoribosyltransferase 0.15 0.0078 6.4E-01 7.5E-01 0.0122 7.0E-01 -0.0126 5.6E-01 0.0599 1.0E-01 -0.0041 6.8E-01 alistipes_shahii 5.4.99.25 trna pseudouridine(55) synthase 0.28 0.0242 4.3E-01 5.8E-01 0.0496 3.9E-01 0.0109 7.8E-01 0.0286 6.7E-01 -0.0165 3.5E-01 alistipes_shahii 4.1.1.23 orotidine-5'-phosphate decarboxylase 0.28 0.0502 1.3E-01 3.3E-01 -0.0080 9.0E-01 -0.0071 8.7E-01 -0.0371 6.2E-01 -0.0268 1.7E-01 alistipes_shahii 2.7.7.60 2-c-methyl-d-erythritol 4-phosphate 0.25 0.0122 7.2E-01 7.9E-01 0.0296 6.5E-01 -0.0041 9.2E-01 0.0818 2.9E-01 -0.0326 1.0E-01 cytidylyltransferase alistipes_shahii 3.5.1.24 choloylglycine hydrolase 0.13 0.0148 5.2E-01 6.4E-01 0.0052 9.0E-01 0.0091 7.4E-01 -0.0420 4.0E-01 -0.0134 3.0E-01 alistipes_shahii 5.99.1.3 dna topoisomerase (atp-hydrolyzing) 0.51 0.0500 3.5E-01 5.0E-01 0.1199 2.4E-01 -0.0157 8.1E-01 0.0377 7.6E-01 -0.0086 7.8E-01 alistipes_shahii 3.6.3.4 cu(2+)-exporting atpase 0.27 0.0623 1.4E-02 1.8E-01 0.0824 7.9E-02 0.0159 6.2E-01 0.0385 5.0E-01 -0.0010 9.5E-01 alistipes_shahii 3.5.1.88 peptide deformylase 0.23 0.0238 4.1E-01 5.6E-01 0.0136 8.0E-01 0.0095 7.9E-01 0.0419 5.1E-01 -0.0164 3.3E-01 alistipes_shahii 1.1.1.85 3-isopropylmalate dehydrogenase 0.24 0.0210 4.5E-01 5.9E-01 0.0379 4.4E-01 -0.0099 7.8E-01 -0.0124 8.4E-01 -0.0059 7.1E-01 alistipes_shahii 2.5.1.75 trna dimethylallyltransferase 0.22 0.0254 3.3E-01 5.0E-01 0.0075 8.8E-01 0.0214 5.2E-01 0.0401 5.0E-01 -0.0102 5.1E-01 alistipes_shahii 3.5.99.6 glucosamine-6-phosphate deaminase 0.38 0.0760 1.1E-01 3.3E-01 0.0698 4.4E-01 0.0027 9.6E-01 0.0017 9.9E-01 -0.0196 4.7E-01 alistipes_shahii 1.2.7.3 2-oxoglutarate synthase 0.43 0.0713 1.7E-01 3.7E-01 0.0668 5.0E-01 -0.0968 1.3E-01 0.0920 4.4E-01 -0.0278 3.6E-01 alistipes_shahii 3.1.3.5 5'-nucleotidase 0.36 0.0282 3.6E-01 5.2E-01 0.1216 3.3E-02 0.0244 5.2E-01 0.0126 8.5E-01 0.0055 7.5E-01 alistipes_shahii 1.16.3.2 bacterial non-heme ferritin 0.35 0.0401 4.2E-01 5.7E-01 0.0678 4.7E-01 -0.0148 8.1E-01 -0.0357 7.5E-01 -0.0191 5.1E-01 alistipes_shahii 1.2.1.38 n-acetyl-gamma-glutamyl-phosphate 0.26 0.0292 3.6E-01 5.2E-01 0.0255 6.7E-01 -0.0886 2.9E-02 0.0304 6.7E-01 -0.0132 4.8E-01 reductase alistipes_shahii 4.2.1.49 urocanate hydratase 0.42 0.0519 2.2E-01 4.1E-01 0.1204 1.3E-01 -0.0428 4.2E-01 0.0685 4.8E-01 0.0040 8.7E-01 alistipes_shahii 4.2.1.20 tryptophan synthase 0.15 0.0232 2.1E-01 4.0E-01 0.0789 2.0E-02 -0.0094 6.9E-01 0.0492 2.3E-01 -0.0155 1.5E-01 65

Supplementary Data 4b Enzyme Detectio Plasma TMAO Choline Choline Red meat Red meat Species Enzyme Name ID n Rate Effect P FDR Effect P Effect P Effect P Effect P alistipes_shahii 1.5.1.20 methylenetetrahydrofolate reductase 0.27 0.0512 1.1E-01 3.3E-01 0.0746 2.1E-01 -0.0273 5.0E-01 0.0869 2.2E-01 -0.0208 2.6E-01 (nad(p)h) alistipes_shahii 2.7.7.38 3-deoxy-manno-octulosonate 0.3 0.0506 2.1E-01 4.0E-01 -0.0128 8.6E-01 -0.0399 4.3E-01 0.0198 8.3E-01 -0.0269 2.5E-01 cytidylyltransferase alistipes_shahii 6.3.2.17 tetrahydrofolate synthase 0.24 0.0304 1.1E-01 3.3E-01 0.0177 6.2E-01 -0.0013 9.6E-01 0.0123 7.7E-01 -0.0138 2.1E-01 alistipes_shahii 2.3.1.39 [acyl-carrier-protein] s- 0.3 0.0182 5.7E-01 6.8E-01 0.0846 1.5E-01 0.0589 1.4E-01 0.0450 5.2E-01 -0.0018 9.2E-01 malonyltransferase alistipes_shahii 2.4.2.10 orotate phosphoribosyltransferase 0.24 -0.0203 5.6E-01 6.8E-01 -0.0317 6.4E-01 -0.0315 4.6E-01 -0.0354 6.6E-01 -0.0239 2.3E-01 alistipes_shahii 2.1.1.63 methylated-dna--[protein]-cysteine s- 0.11 -0.0023 9.1E-01 9.3E-01 0.0797 4.4E-02 -0.0258 3.3E-01 0.1484 1.2E-03 -0.0101 4.2E-01 methyltransferase alistipes_shahii 4.2.1.46 dtdp-glucose 4,6-dehydratase 0.36 0.0172 5.4E-01 6.6E-01 0.0301 5.7E-01 -0.0613 8.3E-02 0.0256 6.8E-01 -0.0071 6.7E-01 alistipes_shahii 2.7.1.148 4-(cytidine 5'-diphospho)-2-c-methyl-d- 0.3 0.0158 7.0E-01 7.7E-01 0.1158 1.2E-01 0.0075 8.8E-01 0.0170 8.5E-01 0.0223 3.4E-01 erythritol kinase alistipes_shahii 3.1.3.18 phosphoglycolate phosphatase 0.15 0.0341 1.4E-01 3.4E-01 0.0254 5.6E-01 -0.0294 3.2E-01 0.0103 8.5E-01 -0.0057 6.8E-01 alistipes_shahii 6.1.1.21 histidine--trna ligase 0.3 0.0402 1.2E-01 3.3E-01 0.0363 4.6E-01 -0.0130 6.8E-01 -0.0505 3.9E-01 -0.0098 5.1E-01 alistipes_shahii 6.3.4.19 trna(ile)-lysidine synthetase 0.25 0.0376 1.3E-01 3.3E-01 -0.0131 7.8E-01 -0.0163 5.9E-01 0.0041 9.4E-01 -0.0162 2.5E-01 alistipes_shahii 2.1.1.33 trna (guanine(46)-n(7))- 0.23 0.0343 1.7E-01 3.7E-01 0.0009 9.8E-01 -0.0311 3.2E-01 -0.0880 1.1E-01 -0.0134 3.6E-01 methyltransferase alistipes_shahii 6.3.5.1 nad(+) synthase (glutamine- 0.46 0.0517 2.5E-01 4.3E-01 0.0626 4.5E-01 -0.0584 3.0E-01 0.0122 9.0E-01 -0.0256 3.2E-01 hydrolyzing) alistipes_shahii 3.6.1.27 undecaprenyl-diphosphate 0.29 0.0457 2.0E-01 3.9E-01 0.1371 3.7E-02 -0.0100 8.2E-01 0.0250 7.5E-01 -0.0085 6.8E-01 phosphatase alistipes_shahii 1.8.98.1 cob--com heterodisulfide reductase 0.31 0.0988 1.2E-02 1.8E-01 0.0513 4.8E-01 -0.0315 5.3E-01 0.0063 9.4E-01 -0.0230 3.2E-01 alistipes_shahii 3.5.1.14 n-acyl-aliphatic-l-amino acid 0.24 0.0127 6.7E-01 7.6E-01 -0.0156 7.8E-01 -0.0177 6.3E-01 -0.0588 3.8E-01 -0.0175 3.0E-01 amidohydrolase alistipes_shahii 5.3.1.13 arabinose-5-phosphate Isomerase 0.35 0.0334 4.3E-01 5.8E-01 0.1076 1.7E-01 -0.0236 6.6E-01 -0.0309 7.5E-01 -0.0065 7.9E-01 alistipes_shahii 2.3.1.29 glycine c-acetyltransferase 0.39 0.0493 2.6E-01 4.4E-01 0.1008 2.3E-01 -0.0389 4.8E-01 0.0357 7.2E-01 -0.0256 3.1E-01 alistipes_shahii 1.3.99.22 coproporphyrinogen dehydrogenase 0.27 0.0129 6.9E-01 7.7E-01 0.0402 5.0E-01 -0.0226 5.7E-01 -0.0290 6.8E-01 -0.0120 5.2E-01 alistipes_shahii 3.5.4.12 dcmp deaminase 0.24 0.0153 6.3E-01 7.4E-01 0.0546 3.5E-01 -0.0062 8.8E-01 0.0967 1.6E-01 -0.0068 7.1E-01 alistipes_shahii 6.1.1.15 proline--trna ligase 0.42 0.0444 2.1E-01 4.0E-01 0.0467 4.9E-01 0.0151 7.3E-01 0.0915 2.6E-01 -0.0115 5.8E-01 alistipes_shahii 1.17.1.2 4-hydroxy-3-methylbut-2-enyl 0.24 0.0508 5.5E-02 2.6E-01 0.0423 3.9E-01 0.0243 4.7E-01 0.0954 1.0E-01 -0.0086 5.8E-01 diphosphate reductase alistipes_shahii 2.7.4.3 adenylate kinase 0.18 0.0548 3.1E-02 2.2E-01 0.0190 6.9E-01 -0.0494 1.2E-01 0.0448 4.2E-01 -0.0245 9.3E-02 alistipes_shahii 6.3.5.2 gmp synthase (glutamine-hydrolyzing) 0.4 0.1193 1.3E-02 1.8E-01 0.0634 4.8E-01 -0.0118 8.4E-01 0.0200 8.6E-01 -0.0070 8.0E-01

alistipes_shahii 3.4.13.3 transferred entry: 3.4.13.18 and 0.45 0.0630 1.6E-01 3.6E-01 0.1102 1.9E-01 -0.0006 9.9E-01 0.1132 2.7E-01 -0.0138 6.0E-01 3.4.13.20 alistipes_shahii 3.1.21.2 deoxyribonuclease Iv 0.35 0.0524 1.8E-01 3.8E-01 -0.0270 7.2E-01 0.0320 5.1E-01 0.0559 5.3E-01 -0.0018 9.4E-01 alistipes_shahii 4.1.1.11 aspartate 1-decarboxylase 0.13 0.0213 2.1E-01 4.0E-01 0.0178 5.5E-01 -0.0137 5.2E-01 0.0017 9.6E-01 -0.0119 2.3E-01 alistipes_shahii 1.3.99.5 3-oxo-5-alpha-steroid 4- 0.23 0.0352 1.7E-01 3.7E-01 0.0051 9.1E-01 0.0128 6.9E-01 0.0016 9.8E-01 -0.0073 6.3E-01 dehydrogenase (acceptor) alistipes_shahii 5.3.1.9 glucose-6-phosphate Isomerase 0.38 0.0200 5.9E-01 7.0E-01 0.0712 3.0E-01 -0.0097 8.4E-01 0.0067 9.4E-01 -0.0288 1.8E-01 alistipes_shahii 2.4.2.1 purine-nucleoside phosphorylase 0.4 0.0645 1.9E-01 3.8E-01 0.1043 2.6E-01 0.0371 5.4E-01 0.0985 3.8E-01 0.0001 1.0E+00 alistipes_shahii 2.1.1.297 peptide chain release factor n(5)- 0.35 0.0756 1.7E-01 3.7E-01 0.0741 4.8E-01 -0.0890 1.9E-01 0.0529 6.7E-01 -0.0035 9.1E-01 glutamine methyltransferase alistipes_shahii 5.3.1.12 glucuronate Isomerase 0.28 0.0204 4.1E-01 5.6E-01 0.0046 9.2E-01 -0.0158 6.1E-01 0.0639 2.5E-01 -0.0223 1.2E-01 alistipes_shahii 2.1.2.10 aminomethyltransferase 0.32 0.0264 5.0E-01 6.3E-01 0.0403 5.8E-01 0.0152 7.5E-01 0.0302 7.3E-01 0.0032 8.9E-01 alistipes_shahii 2.8.1.7 cysteine desulfurase 0.35 0.0603 1.7E-01 3.6E-01 0.0659 4.2E-01 -0.0156 7.7E-01 0.0543 5.8E-01 -0.0027 9.2E-01 alistipes_shahii 5.1.3.1 ribulose-phosphate 3-epimerase 0.28 0.0497 2.8E-01 4.4E-01 0.0548 5.3E-01 0.0334 5.5E-01 0.0121 9.1E-01 -0.0120 6.5E-01 alistipes_shahii 3.2.1.22 alpha-galactosidase 0.34 -0.0002 1.0E+00 1.0E+00 0.0477 3.8E-01 -0.0502 1.7E-01 -0.0475 4.7E-01 -0.0106 5.3E-01 alistipes_shahii 2.3.1.234 n(6)-l-threonylcarbamoyladenine 0.23 0.0311 1.5E-01 3.4E-01 0.0685 9.1E-02 0.0278 3.2E-01 -0.0089 8.5E-01 -0.0068 6.0E-01 synthase alistipes_shahii 1.4.1.1 alanine dehydrogenase 0.32 0.0696 7.1E-02 2.8E-01 0.0902 2.2E-01 -0.0199 6.8E-01 -0.0051 9.5E-01 -0.0100 6.5E-01 alistipes_shahii 3.5.2.7 Imidazolonepropionase 0.34 0.0661 1.2E-01 3.3E-01 0.0742 3.6E-01 -0.0016 9.8E-01 -0.0097 9.2E-01 -0.0069 7.8E-01 alistipes_shahii 3.1.4.46 glycerophosphodiester 0.33 0.0359 2.4E-01 4.3E-01 0.0137 8.1E-01 0.0213 5.9E-01 0.0569 4.1E-01 -0.0290 1.1E-01 phosphodiesterase alistipes_shahii 6.1.1.5 Isoleucine--trna ligase 0.37 0.0252 2.9E-01 4.6E-01 -0.0287 5.3E-01 -0.0413 1.7E-01 0.0291 5.9E-01 -0.0240 8.7E-02 alistipes_shahii 4.2.1.2 fumarate hydratase 0.41 0.0575 1.4E-01 3.4E-01 0.1017 1.7E-01 -0.0219 6.5E-01 0.0529 5.6E-01 -0.0262 2.5E-01 alistipes_shahii 6.2.1.1 acetate--coa ligase 0.3 0.0196 4.8E-01 6.2E-01 0.0820 1.1E-01 -0.0431 2.2E-01 0.0688 2.7E-01 -0.0104 5.2E-01 alistipes_shahii 3.4.11.9 xaa-pro aminopeptidase 0.41 0.0513 2.7E-01 4.4E-01 0.0508 5.7E-01 -0.0133 8.2E-01 0.0418 7.0E-01 -0.0148 5.8E-01 alistipes_shahii 2.3.1.129 acyl-[acyl-carrier-protein]--udp-n- 0.33 0.0546 1.4E-01 3.3E-01 0.0776 2.4E-01 0.0207 6.6E-01 0.0800 3.2E-01 -0.0195 3.7E-01 acetylglucosamine o-acyltransferase alistipes_shahii 6.3.4.15 biotin--[acetyl-coa-carboxylase] ligase 0.38 0.0448 4.1E-01 5.6E-01 0.2782 5.9E-03 -0.0560 4.0E-01 0.0826 5.1E-01 -0.0026 9.3E-01

alistipes_shahii 4.3.99.3 7-carboxy-7-deazaguanine synthase 0.23 0.0087 7.9E-01 8.5E-01 0.0616 3.1E-01 -0.0421 3.0E-01 -0.0037 9.6E-01 -0.0181 3.3E-01 alistipes_shahii 2.7.8.8 cdp-diacylglycerol--serine o- 0.19 0.0262 3.1E-01 4.7E-01 -0.0424 3.8E-01 -0.0206 5.2E-01 -0.0356 5.3E-01 -0.0275 6.6E-02 phosphatidyltransferase alistipes_shahii 1.17.1.8 4-hydroxy-tetrahydrodipicolinate 0.35 0.0557 2.3E-01 4.1E-01 0.0081 9.2E-01 -0.1301 2.4E-02 -0.0478 6.5E-01 -0.0297 2.7E-01 reductase alistipes_shahii 1.1.1.22 udp-glucose 6-dehydrogenase 0.26 0.0320 2.7E-01 4.4E-01 0.0586 2.8E-01 0.0173 6.3E-01 0.0419 5.2E-01 -0.0130 4.4E-01 alistipes_shahii 1.6.5.8 nadh:ubiquinone reductase (na(+)- 0.45 0.0506 1.2E-01 3.3E-01 0.0621 3.1E-01 -0.0529 1.9E-01 0.0226 7.6E-01 -0.0172 3.6E-01 transporting) 66

Supplementary Data 4b Enzyme Detectio Plasma TMAO Choline Choline Red meat Red meat Species Enzyme Name ID n Rate Effect P FDR Effect P Effect P Effect P Effect P alistipes_shahii ungrouped no_name 0.6 0.0491 1.2E-01 3.3E-01 0.0751 2.0E-01 -0.0440 2.6E-01 0.0503 4.8E-01 -0.0080 6.6E-01 alistipes_shahii 1.2.1.41 glutamate-5-semialdehyde 0.36 0.0317 5.5E-01 6.7E-01 0.1702 8.2E-02 -0.1159 7.7E-02 0.0506 6.8E-01 -0.0068 8.2E-01 dehydrogenase alistipes_shahii 2.7.7.7 dna-directed dna polymerase 0.49 0.0638 1.9E-01 3.8E-01 0.1188 1.9E-01 -0.0493 4.1E-01 0.0855 4.4E-01 -0.0281 3.2E-01 alistipes_shahii 3.5.1.1 asparaginase 0.22 0.0385 4.4E-02 2.6E-01 0.0303 4.1E-01 -0.0097 6.9E-01 0.0122 7.8E-01 -0.0093 4.0E-01 alistipes_shahii 6.1.1.11 serine--trna ligase 0.28 0.0349 1.9E-01 3.8E-01 0.0113 8.2E-01 -0.0380 2.5E-01 0.0239 6.9E-01 -0.0276 6.9E-02 alistipes_shahii 5.4.99.18 5-(carboxyamino)imidazole 0.17 0.0293 2.1E-01 4.0E-01 0.0089 8.4E-01 0.0049 8.7E-01 0.0046 9.3E-01 -0.0191 1.6E-01 ribonucleotide mutase alistipes_shahii 1.1.1.274 2,5-didehydrogluconate reductase (2- 0.25 0.0108 7.2E-01 7.8E-01 0.0512 3.5E-01 -0.0058 8.8E-01 0.0678 3.0E-01 -0.0037 8.3E-01 dehydro-d-gluconate-forming) alistipes_shahii 1.1.1.205 Imp dehydrogenase 0.38 0.0552 1.3E-01 3.3E-01 0.0385 5.8E-01 -0.0098 8.3E-01 0.0751 3.6E-01 -0.0053 8.0E-01 alistipes_shahii 3.5.4.33 trna(adenine(34)) deaminase 0.11 0.0258 1.7E-01 3.7E-01 -0.0159 6.5E-01 -0.0256 2.8E-01 0.0027 9.5E-01 -0.0169 1.3E-01 alistipes_shahii 4.3.1.1 aspartate ammonia-lyase 0.34 0.0636 6.3E-02 2.7E-01 0.0713 2.7E-01 0.0326 4.4E-01 0.0649 4.0E-01 0.0084 6.7E-01 alistipes_shahii 2.5.1.78 6,7-dimethyl-8-ribityllumazine 0.34 0.0520 2.8E-01 4.4E-01 0.0664 4.6E-01 0.0019 9.7E-01 0.0416 7.0E-01 0.0235 4.0E-01 synthase alistipes_shahii 2.7.4.22 ump kinase 0.37 0.0803 1.1E-01 3.3E-01 0.1532 1.0E-01 0.0359 5.6E-01 0.1446 2.0E-01 0.0092 7.5E-01 alistipes_shahii 1.1.1.28 d-lactate dehydrogenase 0.29 0.0026 9.4E-01 9.5E-01 0.0547 4.0E-01 -0.0131 7.6E-01 0.0018 9.8E-01 -0.0163 4.2E-01 alistipes_shahii 2.5.1.55 3-deoxy-8-phosphooctulonate synthase 0.21 -0.0112 6.7E-01 7.6E-01 0.0034 9.4E-01 -0.0649 4.8E-02 0.0603 2.9E-01 -0.0262 8.6E-02

alistipes_shahii 4.3.3.7 4-hydroxy-tetrahydrodipicolinate 0.37 0.0849 5.6E-02 2.6E-01 0.1669 4.3E-02 -0.0336 5.4E-01 0.1296 2.0E-01 0.0035 8.9E-01 synthase alistipes_shahii 1.17.4.2 ribonucleoside-triphosphate reductase 0.15 0.0080 5.1E-01 6.4E-01 0.0010 9.6E-01 0.0109 4.8E-01 -0.0159 5.5E-01 0.0000 1.0E+00

alistipes_shahii 5.4.99.12 trna pseudouridine(38-40) synthase 0.3 0.0630 9.3E-02 3.1E-01 0.0765 2.8E-01 -0.0034 9.4E-01 0.1003 2.3E-01 -0.0092 6.8E-01 alistipes_shahii 6.3.4.13 phosphoribosylamine--glycine ligase 0.28 0.0377 1.3E-01 3.3E-01 0.0493 2.8E-01 -0.0282 3.6E-01 -0.0237 6.7E-01 -0.0164 2.5E-01 alistipes_shahii 4.2.1.59 3-hydroxyacyl-[acyl-carrier-protein] 0.33 0.0451 1.2E-01 3.3E-01 0.0756 1.6E-01 0.0088 8.1E-01 0.0372 5.6E-01 -0.0121 4.7E-01 dehydratase alistipes_shahii 5.3.1.6 ribose-5-phosphate Isomerase 0.32 0.0583 2.2E-01 4.1E-01 0.0619 4.8E-01 -0.0472 4.3E-01 -0.0355 7.4E-01 -0.0155 5.8E-01 alistipes_shahii 2.4.2.9 uracil phosphoribosyltransferase 0.28 0.0361 2.5E-01 4.3E-01 0.1050 7.4E-02 -0.0067 8.6E-01 0.0488 4.9E-01 -0.0227 2.0E-01 alistipes_shahii 2.5.1.9 riboflavin synthase 0.36 0.0612 1.9E-01 3.9E-01 0.0275 7.6E-01 -0.0717 2.2E-01 -0.0063 9.5E-01 -0.0225 4.1E-01 alistipes_shahii 2.4.2.29 trna-guanine(34) transglycosylase 0.33 0.0252 5.2E-01 6.4E-01 0.0326 6.6E-01 -0.0120 8.1E-01 0.0225 8.0E-01 -0.0027 9.0E-01 alistipes_shahii 2.3.1.117 2,3,4,5-tetrahydropyridine-2,6- 0.43 0.0642 2.8E-01 4.4E-01 0.1363 2.2E-01 -0.0593 4.2E-01 0.0267 8.5E-01 -0.0089 7.9E-01 dicarboxylate n-succinyltransferase alistipes_shahii 1.8.1.9 thioredoxin-disulfide reductase 0.32 0.0592 9.6E-02 3.2E-01 0.0504 4.5E-01 -0.0144 7.4E-01 0.0366 6.5E-01 -0.0319 1.2E-01 alistipes_shahii 4.1.2.25 dihydroneopterin aldolase 0.17 0.0057 8.4E-01 8.8E-01 0.0085 8.7E-01 -0.0071 8.4E-01 0.0518 4.1E-01 -0.0067 6.8E-01 alistipes_shahii 1.11.1.15 peroxiredoxin 0.28 0.0672 5.5E-02 2.6E-01 0.0446 5.0E-01 0.0308 4.8E-01 0.1256 1.1E-01 -0.0290 1.5E-01 alistipes_shahii 2.7.1.11 6-phosphofructokinase 0.32 0.0978 6.3E-03 1.8E-01 0.0503 4.5E-01 -0.0156 7.3E-01 0.0546 5.0E-01 -0.0078 7.1E-01 alistipes_shahii 2.6.1.11 acetylornithine transaminase 0.35 0.0480 2.3E-01 4.2E-01 0.0830 2.6E-01 -0.0766 1.3E-01 0.0525 5.6E-01 -0.0078 7.4E-01 alistipes_shahii 2.7.1.21 thymidine kinase 0.24 0.0350 2.2E-01 4.1E-01 -0.0058 9.1E-01 0.0024 9.5E-01 0.0091 8.9E-01 -0.0158 3.4E-01 alistipes_shahii 2.5.1.19 3-phosphoshikimate 1- 0.4 0.0761 2.8E-01 4.5E-01 0.0174 9.0E-01 -0.0825 3.4E-01 -0.0300 8.5E-01 0.0204 6.2E-01 carboxyvinyltransferase alistipes_shahii 6.3.4.5 argininosuccinate synthase 0.35 0.0706 5.7E-02 2.6E-01 0.1824 7.8E-03 -0.0101 8.3E-01 0.1005 2.3E-01 -0.0004 9.8E-01 alistipes_shahii 5.3.1.8 mannose-6-phosphate Isomerase 0.29 0.0338 3.0E-01 4.6E-01 0.0536 3.8E-01 -0.0374 3.5E-01 0.0277 7.0E-01 -0.0246 1.9E-01 alistipes_shahii 1.1.1.3 homoserine dehydrogenase 0.3 0.0329 2.2E-01 4.1E-01 0.0695 1.7E-01 0.0039 9.1E-01 0.0950 1.2E-01 -0.0164 2.9E-01 alistipes_shahii 3.2.1.52 beta-n-acetylhexosaminidase 0.11 -0.0142 1.5E-01 3.5E-01 -0.0043 8.0E-01 0.0001 1.0E+00 0.0257 2.3E-01 -0.0144 1.3E-02 alistipes_shahii 2.1.2.2 phosphoribosylglycinamide 0.28 0.0022 9.6E-01 9.7E-01 0.0402 6.1E-01 0.0595 2.6E-01 -0.0322 7.3E-01 -0.0131 5.9E-01 formyltransferase alistipes_shahii 2.4.99.17 s-adenosylmethionine:trna 0.38 0.0243 4.0E-01 5.5E-01 0.0836 1.2E-01 -0.0106 7.7E-01 0.0285 6.6E-01 -0.0338 4.4E-02 ribosyltransferase-isomerase alistipes_shahii 4.1.2.4 deoxyribose-phosphate aldolase 0.4 0.0296 5.5E-01 6.7E-01 -0.0053 9.5E-01 -0.0824 1.8E-01 -0.0590 5.9E-01 -0.0601 3.4E-02 alistipes_shahii 2.7.2.3 phosphoglycerate kinase 0.38 0.0461 2.0E-01 3.9E-01 0.0724 2.9E-01 0.0208 6.5E-01 -0.0363 6.5E-01 -0.0425 4.3E-02 alistipes_shahii 5.4.2.12 phosphoglycerate mutase (2,3- 0.34 0.0414 1.6E-01 3.6E-01 0.0315 5.7E-01 0.0325 3.8E-01 -0.0131 8.4E-01 -0.0337 4.7E-02 diphosphoglycerate-independent) alistipes_shahii 3.5.1.11 penicillin amidase 0.13 0.0148 5.2E-01 6.4E-01 0.0052 9.0E-01 0.0091 7.4E-01 -0.0420 4.0E-01 -0.0134 3.0E-01 alistipes_shahii 1.8.4.11 peptide-methionine (s)-s-oxide 0.37 0.0068 9.1E-01 9.3E-01 0.0625 5.8E-01 -0.0847 2.6E-01 0.0145 9.2E-01 -0.0154 6.6E-01 reductase alistipes_shahii 6.4.1.3 propionyl-coa carboxylase 0.49 0.0852 6.7E-02 2.7E-01 0.1015 2.5E-01 -0.0393 5.0E-01 -0.0238 8.2E-01 -0.0340 2.1E-01 alistipes_shahii 6.3.2.9 udp-n-acetylmuramoyl-l-alanine--d- 0.22 0.0172 3.6E-01 5.1E-01 0.0405 2.4E-01 0.0056 8.1E-01 0.0273 5.1E-01 -0.0141 1.9E-01 glutamate ligase alistipes_shahii 3.2.1.1 alpha-amylase 0.41 0.0551 2.5E-01 4.3E-01 0.0341 7.1E-01 -0.0240 6.9E-01 0.1465 1.8E-01 -0.0114 6.8E-01 alistipes_shahii 2.7.4.25 (d)cmp kinase 0.22 0.0376 1.9E-01 3.8E-01 -0.0041 9.4E-01 -0.0153 6.7E-01 -0.0548 3.9E-01 -0.0116 4.9E-01 alistipes_shahii 2.6.99.2 pyridoxine 5'-phosphate synthase 0.28 0.0780 4.1E-02 2.5E-01 0.0618 3.9E-01 0.0012 9.8E-01 0.0480 5.7E-01 -0.0255 2.4E-01 alistipes_shahii 6.1.1.2 tryptophan--trna ligase 0.26 0.0102 6.7E-01 7.6E-01 0.0740 9.4E-02 0.0727 1.6E-02 -0.0231 6.6E-01 -0.0133 3.5E-01 alistipes_shahii 2.5.1.72 quinolinate synthase 0.27 -0.0133 6.5E-01 7.5E-01 0.0534 3.3E-01 0.0165 6.6E-01 0.0948 1.4E-01 -0.0068 6.9E-01 alistipes_shahii 4.2.1.33 3-isopropylmalate dehydratase 0.38 0.0336 4.3E-01 5.8E-01 0.1020 1.9E-01 -0.0695 1.9E-01 0.1572 1.1E-01 0.0032 9.0E-01 alistipes_shahii 3.3.1.1 adenosylhomocysteinase 0.3 0.0573 2.3E-02 2.0E-01 0.0214 6.6E-01 0.0131 6.8E-01 0.0370 5.1E-01 -0.0010 9.5E-01 alistipes_shahii 3.1.26.5 ribonuclease p 0.13 -0.0153 5.1E-01 6.4E-01 -0.0306 4.8E-01 0.0497 8.8E-02 -0.0743 1.4E-01 -0.0190 1.6E-01 alistipes_shahii 1.6.5.11 nadh dehydrogenase (quinone) 0.39 0.0105 7.0E-01 7.7E-01 0.0408 4.4E-01 -0.0190 5.8E-01 0.0037 9.5E-01 -0.0128 4.2E-01 alistipes_shahii 1.1.1.290 4-phosphoerythronate dehydrogenase 0.33 0.0140 7.4E-01 8.0E-01 0.0241 7.6E-01 -0.0150 7.7E-01 -0.0055 9.5E-01 -0.0521 2.9E-02 alistipes_shahii 1.1.1.133 dtdp-4-dehydrorhamnose reductase 0.25 0.0096 7.7E-01 8.3E-01 0.0270 6.5E-01 -0.0072 8.6E-01 0.0926 1.9E-01 -0.0180 3.3E-01 alistipes_shahii 3.4.21.89 signal peptidase I 0.34 0.0138 6.8E-01 7.7E-01 0.0189 7.7E-01 -0.0278 5.1E-01 0.0826 2.9E-01 -0.0151 4.4E-01 alistipes_shahii 2.7.1.130 tetraacyldisaccharide 4'-kinase 0.39 0.0558 2.9E-01 4.5E-01 0.1165 2.4E-01 0.0034 9.6E-01 0.1879 1.1E-01 -0.0030 9.2E-01 67

Supplementary Data 4b Enzyme Detectio Plasma TMAO Choline Choline Red meat Red meat Species Enzyme Name ID n Rate Effect P FDR Effect P Effect P Effect P Effect P alistipes_shahii 2.3.1.18 galactoside o-acetyltransferase 0.24 0.0912 2.0E-02 2.0E-01 -0.0271 7.1E-01 -0.0033 9.5E-01 0.0220 8.0E-01 -0.0272 2.3E-01 alistipes_shahii 5.1.3.13 dtdp-4-dehydrorhamnose 3,5- 0.16 0.0684 1.0E-03 1.0E-01 0.0137 7.2E-01 0.0219 4.1E-01 0.0044 9.2E-01 -0.0106 3.9E-01 epimerase alistipes_shahii 6.1.1.1 tyrosine--trna ligase 0.39 0.0339 3.4E-01 5.0E-01 0.1063 1.1E-01 0.0031 9.4E-01 0.0144 8.6E-01 -0.0115 5.7E-01 alistipes_shahii 3.6.4.12 dna helicase 0.44 0.0288 3.5E-01 5.1E-01 0.1202 3.6E-02 -0.0550 1.5E-01 0.0405 5.6E-01 -0.0215 2.3E-01 alistipes_shahii 2.6.1.16 glutamine--fructose-6-phosphate 0.26 0.0501 2.0E-02 2.0E-01 -0.0284 4.9E-01 0.0045 8.7E-01 0.0032 9.5E-01 -0.0096 4.6E-01 transaminase (isomerizing) alistipes_shahii 3.2.1.45 glucosylceramidase 0.26 0.0325 2.7E-01 4.4E-01 0.0173 7.5E-01 -0.0446 2.3E-01 0.0218 7.4E-01 -0.0196 2.5E-01 alistipes_shahii 2.5.1.6 methionine adenosyltransferase 0.37 0.0650 1.1E-01 3.3E-01 0.0528 4.9E-01 0.0005 9.9E-01 0.0988 2.9E-01 -0.0062 7.9E-01 alistipes_shahii 1.3.1.12 prephenate dehydrogenase 0.37 0.0342 4.4E-01 5.8E-01 0.0633 4.4E-01 -0.0043 9.4E-01 0.0512 6.0E-01 0.0024 9.2E-01 alistipes_shahii 6.1.1.22 asparagine--trna ligase 0.4 0.0385 3.7E-01 5.3E-01 0.0441 5.8E-01 -0.0693 1.9E-01 0.0182 8.5E-01 -0.0329 1.8E-01 alistipes_shahii 3.2.2.1 purine nucleosidase 0.11 0.0150 3.1E-01 4.7E-01 -0.0114 6.9E-01 -0.0012 9.5E-01 0.0568 9.4E-02 -0.0025 7.7E-01 alistipes_shahii 4.1.99.1 tryptophanase 0.38 0.0497 3.4E-01 5.0E-01 -0.0108 9.1E-01 -0.0096 8.8E-01 -0.0491 6.8E-01 -0.0103 7.3E-01 alistipes_shahii 5.4.2.6 beta-phosphoglucomutase 0.14 0.0085 6.7E-01 7.6E-01 0.0007 9.9E-01 -0.0089 7.2E-01 0.0337 4.4E-01 -0.0130 2.7E-01 alistipes_shahii 2.7.4.16 thiamine-phosphate kinase 0.43 0.0706 1.2E-01 3.3E-01 0.0695 4.2E-01 -0.0440 4.4E-01 0.1173 2.6E-01 -0.0066 8.0E-01 alistipes_shahii 2.4.1.1 glycogen phosphorylase 0.43 0.0395 1.7E-01 3.7E-01 0.0634 2.4E-01 -0.0673 6.2E-02 0.0739 2.5E-01 -0.0045 7.9E-01 alistipes_shahii 2.1.2.11 3-methyl-2-oxobutanoate 0.27 0.0098 7.9E-01 8.5E-01 0.0917 1.8E-01 -0.0263 5.7E-01 0.0112 8.9E-01 -0.0302 1.6E-01 hydroxymethyltransferase alistipes_shahii 2.7.1.71 shikimate kinase 0.27 0.0216 5.9E-01 7.1E-01 0.0626 4.1E-01 0.0253 6.2E-01 0.1261 1.7E-01 -0.0087 7.1E-01 alistipes_shahii 2.5.1.54 3-deoxy-7-phosphoheptulonate 0.21 0.0363 1.3E-01 3.3E-01 0.0420 3.4E-01 -0.0063 8.3E-01 0.0691 1.9E-01 -0.0113 4.1E-01 synthase alistipes_shahii 6.1.1.19 arginine--trna ligase 0.32 0.0393 1.9E-01 3.8E-01 0.0777 1.7E-01 -0.0075 8.4E-01 0.1492 2.4E-02 0.0068 7.0E-01 alistipes_shahii 4.1.2.13 fructose-bisphosphate aldolase 0.44 0.0477 1.4E-01 3.3E-01 0.1139 5.6E-02 -0.0113 7.8E-01 -0.0066 9.3E-01 -0.0241 1.9E-01 alistipes_shahii 3.6.1.13 adp-ribose diphosphatase 0.23 0.0366 2.4E-01 4.3E-01 -0.0035 9.5E-01 -0.0026 9.5E-01 -0.0022 9.8E-01 0.0159 3.8E-01 alistipes_shahii 1.11.1.6 catalase 0.29 0.0525 9.1E-02 3.1E-01 0.0275 6.4E-01 -0.0534 1.6E-01 -0.0054 9.4E-01 -0.0226 2.0E-01 alistipes_shahii 6.3.4.18 5-(carboxyamino)imidazole 0.27 0.0355 2.4E-01 4.3E-01 0.0501 3.7E-01 -0.0022 9.5E-01 -0.0225 7.4E-01 -0.0232 1.9E-01 ribonucleotide synthase alistipes_shahii 1.2.7.8 Indolepyruvate ferredoxin 0.27 0.0840 6.1E-02 2.7E-01 0.0151 8.5E-01 -0.0605 2.8E-01 0.0572 5.7E-01 -0.0144 5.8E-01 oxidoreductase alistipes_shahii 6.3.3.2 5-formyltetrahydrofolate cyclo-ligase 0.24 0.0680 8.2E-02 2.9E-01 0.0731 3.1E-01 -0.0523 2.8E-01 -0.0033 9.7E-01 -0.0032 8.9E-01 alistipes_shahii 6.1.1.6 lysine--trna ligase 0.42 0.0648 1.3E-01 3.3E-01 0.0889 2.7E-01 0.0460 3.8E-01 0.1454 1.3E-01 -0.0116 6.4E-01 alistipes_shahii 1.1.1.95 phosphoglycerate dehydrogenase 0.42 0.0441 4.3E-01 5.8E-01 0.1519 1.5E-01 -0.0311 6.5E-01 0.1100 3.9E-01 -0.0132 6.8E-01 alistipes_shahii 2.5.1.10 (2e,6e)-farnesyl diphosphate synthase 0.33 0.0244 5.1E-01 6.4E-01 0.0727 3.0E-01 0.0234 6.2E-01 0.0390 6.4E-01 -0.0237 2.8E-01

alistipes_shahii 3.6.1.19 nucleoside-triphosphate diphosphatase 0.12 -0.0017 9.5E-01 9.6E-01 -0.0742 1.0E-01 -0.0319 3.0E-01 0.0504 3.8E-01 0.0178 2.2E-01

alistipes_shahii 1.11.1.5 cytochrome-c peroxidase 0.19 0.0515 1.7E-01 3.7E-01 0.0248 7.3E-01 0.0571 2.1E-01 0.0751 3.8E-01 -0.0252 2.4E-01 alistipes_shahii 3.1.22.4 crossover junction 0.2 0.0475 1.1E-01 3.3E-01 -0.0543 3.3E-01 -0.0524 1.5E-01 -0.0798 2.3E-01 -0.0406 1.6E-02 endodeoxyribonuclease alistipes_shahii 2.7.6.1 ribose-phosphate diphosphokinase 0.31 0.0543 8.3E-02 2.9E-01 0.0033 9.5E-01 -0.0215 5.8E-01 -0.0466 5.1E-01 -0.0105 5.6E-01 alistipes_shahii 2.7.1.23 nad(+) kinase 0.25 0.0330 2.9E-01 4.5E-01 0.0575 3.1E-01 0.0118 7.6E-01 -0.0133 8.5E-01 -0.0181 3.1E-01 alistipes_shahii 2.7.2.11 glutamate 5-kinase 0.39 0.1168 4.6E-02 2.6E-01 0.0244 8.2E-01 -0.1733 1.6E-02 0.0801 5.5E-01 0.0170 6.1E-01 alistipes_shahii 2.7.1.24 dephospho-coa kinase 0.24 0.0351 2.7E-01 4.4E-01 0.0248 6.8E-01 0.0026 9.5E-01 -0.0119 8.7E-01 -0.0302 1.2E-01 alistipes_shahii 6.3.2.1 pantoate--beta-alanine ligase (amp- 0.27 0.0201 4.9E-01 6.3E-01 0.0333 5.4E-01 -0.0261 4.8E-01 0.0520 4.2E-01 -0.0326 5.5E-02 forming) alistipes_shahii 6.3.3.1 phosphoribosylformylglycinamidine 0.33 0.0246 4.1E-01 5.6E-01 0.1070 4.9E-02 0.0118 7.5E-01 0.0283 6.7E-01 -0.0072 6.8E-01 cyclo-ligase alistipes_shahii 3.6.3.34 Iron-chelate-transporting atpase 0.17 0.0410 4.5E-02 2.6E-01 0.0194 6.0E-01 0.0008 9.8E-01 0.0141 7.5E-01 -0.0104 3.9E-01 alistipes_shahii 3.5.1.2 glutaminase 0.17 -0.0060 8.5E-01 8.9E-01 0.0244 6.9E-01 -0.0376 3.5E-01 0.0698 3.3E-01 -0.0111 5.6E-01 alistipes_shahii 1.17.7.3 (e)-4-hydroxy-3-methylbut-2-enyl- 0.31 0.0461 7.3E-02 2.8E-01 0.0485 3.1E-01 -0.0250 4.4E-01 0.0622 2.8E-01 -0.0113 4.5E-01 diphosphate synthase (flavodoxin) alistipes_shahii 4.3.1.3 histidine ammonia-lyase 0.38 0.0752 1.5E-01 3.4E-01 0.1019 2.9E-01 -0.0139 8.3E-01 0.0384 7.4E-01 0.0019 9.5E-01 alistipes_shahii 1.97.1.4 [formate-c-acetyltransferase]- 0.23 0.0250 3.4E-01 5.0E-01 0.0551 2.5E-01 -0.0050 8.8E-01 0.0435 4.5E-01 -0.0093 5.4E-01 activating enzyme alistipes_shahii 6.1.1.20 phenylalanine--trna ligase 0.33 0.0045 8.9E-01 9.2E-01 0.0090 8.9E-01 -0.0120 7.7E-01 0.0013 9.9E-01 -0.0333 7.6E-02 alistipes_shahii 5.4.2.8 phosphomannomutase 0.48 0.1096 4.7E-02 2.6E-01 0.1450 1.6E-01 -0.0132 8.5E-01 0.0557 6.6E-01 -0.0120 7.1E-01 alistipes_shahii 2.7.2.8 acetylglutamate kinase 0.28 0.0371 2.3E-01 4.3E-01 0.0980 9.5E-02 0.0284 4.8E-01 0.0469 5.0E-01 -0.0176 3.4E-01 alistipes_shahii 4.1.1.65 phosphatidylserine decarboxylase 0.23 0.0139 6.1E-01 7.1E-01 0.0436 3.8E-01 0.0459 1.8E-01 0.0189 7.5E-01 -0.0007 9.7E-01 alistipes_shahii 4.4.1.5 lactoylglutathione lyase 0.13 0.0312 1.5E-01 3.5E-01 -0.0177 6.5E-01 -0.0209 4.5E-01 0.0122 8.0E-01 -0.0317 1.3E-02 alistipes_shahii 2.7.8.13 phospho-n-acetylmuramoyl- 0.17 0.0204 2.2E-01 4.1E-01 0.0090 7.7E-01 -0.0166 4.3E-01 0.0516 1.7E-01 -0.0076 4.4E-01 pentapeptide-transferase alistipes_shahii 6.2.1.3 long-chain-fatty-acid--coa ligase 0.45 0.0624 5.2E-02 2.6E-01 0.1150 6.0E-02 -0.0177 6.7E-01 0.0215 7.7E-01 -0.0168 3.8E-01 alistipes_shahii 6.3.4.2 ctp synthase (glutamine hydrolyzing) 0.42 0.0495 2.2E-01 4.1E-01 0.1007 1.9E-01 -0.0259 6.1E-01 0.0025 9.8E-01 -0.0335 1.5E-01 alistipes_shahii 3.4.21.102 c-terminal processing peptidase 0.44 0.0341 2.8E-01 4.4E-01 0.1191 4.4E-02 -0.0221 5.7E-01 0.0803 2.6E-01 -0.0038 8.3E-01 alistipes_shahii 4.6.1.12 2-c-methyl-d-erythritol 2,4- 0.36 0.1067 9.8E-02 3.2E-01 0.0469 7.0E-01 -0.0719 3.7E-01 -0.0248 8.7E-01 -0.0177 6.4E-01 cyclodiphosphate synthase alistipes_shahii 2.3.1.n2 phosphate acyltransferase 0.42 0.0837 9.1E-02 3.1E-01 0.1120 2.3E-01 -0.0059 9.2E-01 0.2186 5.3E-02 -0.0163 5.7E-01 alistipes_shahii 2.7.1.48 uridine kinase 0.41 0.0626 1.2E-01 3.3E-01 0.1006 1.7E-01 -0.0002 1.0E+00 0.0557 5.3E-01 -0.0002 9.9E-01 alistipes_shahii 3.4.23.36 signal peptidase II 0.16 0.0184 3.5E-01 5.1E-01 0.0204 5.8E-01 -0.0143 5.6E-01 -0.0230 6.0E-01 -0.0077 5.0E-01 alistipes_shahii 3.4.11.4 tripeptide aminopeptidase 0.3 0.0035 9.0E-01 9.2E-01 0.0753 1.5E-01 -0.0117 7.4E-01 -0.0078 9.0E-01 -0.0116 4.8E-01 alistipes_shahii 6.3.2.8 udp-n-acetylmuramate--l-alanine 0.26 0.0363 1.0E-01 3.2E-01 0.0419 3.1E-01 -0.0182 5.1E-01 0.0171 7.3E-01 -0.0033 8.0E-01 ligase 68

Supplementary Data 4b Enzyme Detectio Plasma TMAO Choline Choline Red meat Red meat Species Enzyme Name ID n Rate Effect P FDR Effect P Effect P Effect P Effect P alistipes_shahii 4.1.1.15 glutamate decarboxylase 0.27 0.0118 6.9E-01 7.7E-01 0.0461 4.1E-01 -0.0606 1.0E-01 0.0335 6.1E-01 -0.0030 8.6E-01 alistipes_shahii 3.6.3.14 h(+)-transporting two-sector atpase 0.47 0.0548 2.7E-01 4.4E-01 0.0234 8.0E-01 -0.0050 9.3E-01 0.0070 9.5E-01 -0.0280 3.3E-01 alistipes_shahii 2.1.2.1 glycine hydroxymethyltransferase 0.4 0.0616 1.6E-01 3.6E-01 0.1458 7.3E-02 -0.0724 1.8E-01 0.0129 9.0E-01 -0.0287 2.6E-01 alistipes_shahii 2.2.1.6 acetolactate synthase 0.26 -0.0122 6.1E-01 7.2E-01 0.0919 4.7E-02 -0.0144 6.6E-01 0.0011 9.8E-01 -0.0085 5.7E-01 alistipes_shahii 4.2.3.5 chorismate synthase 0.39 0.0705 1.6E-01 3.6E-01 0.0773 4.1E-01 -0.0375 5.5E-01 0.0904 4.3E-01 -0.0163 5.7E-01 alistipes_shahii 6.3.2.10 udp-n-acetylmuramoyl-tripeptide--d- 0.29 0.0417 1.8E-01 3.7E-01 0.0396 4.9E-01 0.0113 7.7E-01 0.0663 3.4E-01 -0.0162 3.6E-01 alanyl-d-alanine ligase eubacterium_hallii 3.5.1.24 choloylglycine hydrolase 0.36 0.0013 8.6E-01 8.9E-01 0.0324 1.3E-02 -0.0048 5.9E-01 -0.0081 6.0E-01 0.0000 9.9E-01 eubacterium_hallii 2.7.1.11 6-phosphofructokinase 0.15 -0.0063 6.7E-01 7.6E-01 -0.0381 1.7E-01 -0.0092 6.2E-01 -0.0618 5.6E-02 -0.0085 3.3E-01 eubacterium_hallii 4.3.3.7 4-hydroxy-tetrahydrodipicolinate 0.24 -0.0301 3.0E-01 4.6E-01 0.0252 6.4E-01 0.0226 5.4E-01 -0.0902 1.6E-01 -0.0176 3.0E-01 synthase eubacterium_hallii 3.4.21.89 signal peptidase I 0.12 -0.0157 4.3E-01 5.8E-01 -0.0341 3.7E-01 0.0025 9.2E-01 -0.0557 2.1E-01 -0.0241 4.2E-02 eubacterium_hallii 2.7.1.16 ribulokinase 0.2 0.0208 2.0E-01 3.9E-01 0.0390 1.9E-01 0.0191 3.5E-01 -0.0121 7.3E-01 -0.0029 7.6E-01 eubacterium_hallii 6.1.1.19 arginine--trna ligase 0.15 -0.0001 9.9E-01 9.9E-01 -0.0251 3.3E-01 0.0010 9.5E-01 -0.0431 1.5E-01 -0.0109 1.6E-01 eubacterium_hallii 6.3.5.2 gmp synthase (glutamine-hydrolyzing) 0.28 0.0359 2.6E-01 4.4E-01 0.0012 9.8E-01 0.0260 5.2E-01 -0.1184 8.9E-02 0.0017 9.3E-01

eubacterium_hallii 5.4.2.12 phosphoglycerate mutase (2,3- 0.13 0.0029 8.7E-01 9.0E-01 -0.0077 7.9E-01 0.0291 1.7E-01 -0.0133 7.2E-01 -0.0076 4.4E-01 diphosphoglycerate-independent) eubacterium_hallii 2.7.1.30 glycerol kinase 0.7 0.0365 5.6E-01 6.8E-01 0.0778 5.2E-01 -0.0234 7.7E-01 -0.1677 2.4E-01 -0.0550 1.4E-01 eubacterium_hallii 2.1.2.1 glycine hydroxymethyltransferase 0.14 0.0185 2.6E-01 4.4E-01 0.0153 6.2E-01 0.0195 3.5E-01 -0.0236 5.1E-01 -0.0092 3.4E-01 eubacterium_hallii 2.7.3.9 phosphoenolpyruvate--protein 0.59 0.0339 5.8E-01 6.9E-01 0.0985 3.9E-01 0.0141 8.5E-01 -0.0786 5.6E-01 -0.0259 4.7E-01 phosphotransferase eubacterium_hallii 4.2.1.10 3-dehydroquinate dehydratase 0.13 -0.0091 6.5E-01 7.5E-01 -0.0005 9.9E-01 -0.0021 9.3E-01 -0.0359 4.1E-01 0.0006 9.6E-01 eubacterium_hallii 6.3.4.5 argininosuccinate synthase 0.19 0.0324 6.1E-02 2.7E-01 0.0243 4.5E-01 0.0383 7.6E-02 -0.0154 6.8E-01 -0.0096 3.4E-01 eubacterium_hallii 4.1.1.49 phosphoenolpyruvate carboxykinase 0.23 0.0392 1.6E-01 3.6E-01 0.0238 6.5E-01 0.0357 3.0E-01 0.0096 8.8E-01 -0.0149 3.5E-01 (atp) eubacterium_hallii 6.3.4.13 phosphoribosylamine--glycine ligase 0.12 0.0036 8.4E-01 8.8E-01 -0.0067 8.3E-01 0.0020 9.3E-01 -0.0074 8.5E-01 -0.0105 3.2E-01 eubacterium_hallii 1.17.1.8 4-hydroxy-tetrahydrodipicolinate 0.23 0.0847 1.3E-02 1.8E-01 0.0021 9.7E-01 0.0372 4.0E-01 -0.0959 2.2E-01 -0.0063 7.6E-01 reductase eubacterium_hallii 2.4.1.21 starch synthase 0.23 -0.0105 5.5E-01 6.7E-01 0.0319 3.6E-01 -0.0208 3.8E-01 -0.0412 3.2E-01 -0.0009 9.3E-01 eubacterium_hallii 1.17.1.2 4-hydroxy-3-methylbut-2-enyl 0.33 -0.0071 8.5E-01 8.9E-01 -0.0130 8.6E-01 0.0163 7.3E-01 -0.0662 4.4E-01 -0.0287 1.9E-01 diphosphate reductase eubacterium_hallii 3.6.5.n1 elongation factor 4 0.1 0.0083 5.2E-01 6.5E-01 0.0029 9.1E-01 0.0313 6.2E-02 -0.0236 4.4E-01 -0.0019 8.1E-01 eubacterium_hallii 6.1.1.6 lysine--trna ligase 0.17 0.0236 5.6E-02 2.6E-01 0.0432 8.1E-02 0.0069 6.9E-01 -0.0032 9.1E-01 0.0004 9.6E-01 eubacterium_hallii 3.6.3.14 h(+)-transporting two-sector atpase 0.54 0.0151 4.9E-01 6.2E-01 -0.0251 5.4E-01 0.0245 3.7E-01 -0.0852 8.1E-02 -0.0045 7.2E-01 eubacterium_hallii 2.7.13.3 histidine kinase 0.31 0.0083 3.3E-02 2.3E-01 0.0046 5.2E-01 0.0020 6.8E-01 -0.0020 8.2E-01 -0.0011 6.3E-01 eubacterium_hallii 6.1.1.15 proline--trna ligase 0.11 0.0158 1.1E-01 3.3E-01 0.0069 7.3E-01 -0.0030 8.3E-01 -0.0234 3.2E-01 -0.0023 7.2E-01 eubacterium_hallii 1.4.1.16 diaminopimelate dehydrogenase 0.19 -0.0034 9.0E-01 9.2E-01 0.0068 8.9E-01 0.0293 3.7E-01 0.0370 5.2E-01 0.0214 1.6E-01 eubacterium_hallii 2.5.1.6 methionine adenosyltransferase 0.62 0.1071 7.6E-02 2.9E-01 0.0176 8.8E-01 -0.0021 9.8E-01 -0.2593 5.2E-02 -0.0355 3.3E-01 eubacterium_hallii 2.1.2.11 3-methyl-2-oxobutanoate 0.12 0.0279 9.3E-02 3.1E-01 -0.0107 7.3E-01 -0.0085 6.9E-01 0.0063 8.6E-01 -0.0055 5.8E-01 hydroxymethyltransferase eubacterium_hallii 2.4.2.7 adenine phosphoribosyltransferase 0.15 0.0479 1.0E-01 3.2E-01 -0.0049 9.3E-01 -0.0024 9.5E-01 -0.0633 3.3E-01 -0.0346 4.3E-02 eubacterium_hallii 6.3.4.3 formate--tetrahydrofolate ligase 0.18 0.0566 2.0E-03 1.3E-01 0.0113 7.4E-01 0.0179 4.3E-01 -0.0082 8.4E-01 -0.0097 3.6E-01 eubacterium_hallii 2.7.7.4 sulfate adenylyltransferase 0.21 0.0164 2.5E-01 4.3E-01 0.0084 7.5E-01 -0.0147 4.1E-01 0.0112 7.1E-01 0.0030 7.2E-01 eubacterium_hallii 1.2.7.8 Indolepyruvate ferredoxin 0.13 0.0264 2.4E-01 4.3E-01 0.0111 7.9E-01 0.0349 2.2E-01 -0.0144 7.7E-01 -0.0097 4.6E-01 oxidoreductase eubacterium_hallii 6.1.1.14 glycine--trna ligase 0.26 0.0260 2.6E-01 4.4E-01 -0.0425 3.2E-01 0.0084 7.8E-01 -0.0126 8.0E-01 -0.0060 6.6E-01 eubacterium_hallii 2.8.1.7 cysteine desulfurase 0.1 0.0108 5.1E-01 6.4E-01 0.0368 2.7E-01 -0.0058 7.9E-01 0.0185 6.4E-01 -0.0019 8.6E-01 eubacterium_hallii 2.4.1.25 4-alpha-glucanotransferase 0.19 0.0061 6.7E-01 7.6E-01 -0.0115 6.7E-01 -0.0004 9.8E-01 -0.0105 7.4E-01 -0.0084 3.3E-01 eubacterium_hallii 2.7.7.7 dna-directed dna polymerase 0.31 0.0157 8.0E-02 2.9E-01 0.0266 9.9E-02 0.0047 6.8E-01 0.0137 4.9E-01 0.0004 9.4E-01 eubacterium_hallii 3.4.21.88 repressor lexa 0.24 -0.0154 7.5E-01 8.1E-01 0.0422 6.4E-01 0.0441 4.7E-01 0.0357 7.4E-01 0.0199 4.8E-01 eubacterium_hallii 1.1.1.42 Isocitrate dehydrogenase (nadp(+)) 0.13 -0.0075 6.7E-01 7.6E-01 -0.0722 3.7E-02 -0.0186 4.3E-01 -0.0295 4.7E-01 -0.0086 4.3E-01 eubacterium_hallii 5.4.2.10 phosphoglucosamine mutase 0.17 0.0333 1.4E-01 3.4E-01 -0.0022 9.6E-01 0.0260 3.6E-01 0.0429 4.0E-01 0.0072 5.9E-01 eubacterium_hallii 6.2.1.30 phenylacetate--coa ligase 0.12 0.0187 2.7E-01 4.4E-01 0.0247 4.3E-01 0.0214 3.2E-01 -0.0308 4.1E-01 -0.0110 2.7E-01 eubacterium_hallii 2.7.7.24 glucose-1-phosphate 0.17 0.0154 5.4E-01 6.6E-01 0.0489 3.0E-01 -0.0014 9.6E-01 -0.0455 4.1E-01 -0.0073 6.2E-01 thymidylyltransferase eubacterium_hallii 6.3.4.4 adenylosuccinate synthase 0.15 0.0076 7.1E-01 7.7E-01 0.0329 3.8E-01 0.0473 6.1E-02 -0.0212 6.3E-01 -0.0030 8.0E-01 eubacterium_hallii 2.7.7.27 glucose-1-phosphate 0.31 0.0589 6.4E-02 2.7E-01 0.0084 8.9E-01 0.0752 6.0E-02 -0.0503 4.8E-01 -0.0307 1.0E-01 adenylyltransferase eubacterium_hallii 1.1.1.205 Imp dehydrogenase 0.25 0.0403 1.5E-01 3.5E-01 0.0037 9.4E-01 0.0321 3.6E-01 -0.0120 8.5E-01 -0.0173 2.9E-01 eubacterium_hallii 2.6.1.52 phosphoserine transaminase 0.11 0.0238 7.9E-02 2.9E-01 -0.0219 3.8E-01 0.0154 3.7E-01 -0.0145 6.2E-01 0.0024 7.6E-01 eubacterium_hallii 2.1.1.199 16s rrna (cytosine(1402)-n(4))- 0.15 0.0094 4.9E-01 6.3E-01 -0.0134 6.0E-01 0.0091 6.0E-01 -0.0200 5.1E-01 0.0001 9.9E-01 methyltransferase eubacterium_hallii 5.99.1.2 dna topoisomerase 0.1 0.0104 3.1E-01 4.7E-01 0.0279 1.5E-01 0.0098 4.6E-01 0.0175 4.5E-01 -0.0002 9.8E-01 eubacterium_hallii 3.4.11.18 methionyl aminopeptidase 0.1 -0.0099 4.5E-01 5.9E-01 -0.0362 1.3E-01 -0.0051 7.5E-01 0.0023 9.4E-01 -0.0028 7.1E-01 eubacterium_hallii 6.1.1.3 threonine--trna ligase 0.13 0.0138 2.0E-01 3.9E-01 0.0099 6.2E-01 0.0002 9.9E-01 -0.0085 7.2E-01 0.0046 4.6E-01 eubacterium_hallii 6.3.2.4 d-alanine--d-alanine ligase 0.14 0.0354 1.4E-01 3.4E-01 -0.0112 8.1E-01 0.0099 7.6E-01 -0.0818 1.3E-01 -0.0125 4.0E-01 eubacterium_hallii 2.7.2.3 phosphoglycerate kinase 0.41 0.0169 6.6E-01 7.5E-01 -0.0491 4.9E-01 0.0378 4.4E-01 -0.0807 3.3E-01 -0.0236 3.0E-01 eubacterium_hallii ungrouped no_name 0.87 0.0239 1.3E-01 3.3E-01 0.0016 9.6E-01 0.0027 8.9E-01 -0.0509 1.5E-01 -0.0126 1.8E-01 eubacterium_hallii 2.1.2.2 phosphoribosylglycinamide 0.11 0.0361 6.3E-02 2.7E-01 -0.0452 2.1E-01 0.0169 4.9E-01 -0.0848 4.8E-02 -0.0156 1.7E-01 formyltransferase eubacterium_hallii 6.1.1.18 glutamine--trna ligase 0.12 0.0197 1.9E-01 3.9E-01 -0.0289 3.1E-01 0.0071 7.0E-01 -0.0566 9.1E-02 -0.0099 2.6E-01 69

Supplementary Data 4b Enzyme Detectio Plasma TMAO Choline Choline Red meat Red meat Species Enzyme Name ID n Rate Effect P FDR Effect P Effect P Effect P Effect P eubacterium_hallii 4.2.1.46 dtdp-glucose 4,6-dehydratase 0.1 0.0082 6.0E-01 7.1E-01 -0.0170 5.5E-01 0.0234 2.3E-01 0.0049 8.9E-01 0.0038 6.8E-01 eubacterium_hallii 2.7.1.144 tagatose-6-phosphate kinase 0.12 0.0234 2.0E-01 3.9E-01 0.0101 7.6E-01 -0.0111 6.3E-01 0.0027 9.4E-01 -0.0092 3.9E-01 eubacterium_hallii 5.3.1.1 triose-phosphate Isomerase 0.27 0.0337 2.4E-01 4.3E-01 -0.0188 7.2E-01 0.0442 2.1E-01 -0.0763 2.3E-01 -0.0020 9.0E-01 eubacterium_hallii 2.7.7.6 dna-directed rna polymerase 0.32 0.0114 7.1E-01 7.8E-01 -0.0686 2.6E-01 -0.0005 9.9E-01 -0.0371 6.1E-01 -0.0060 7.6E-01 eubacterium_hallii 2.2.1.2 transaldolase 0.26 -0.0033 9.1E-01 9.3E-01 -0.0319 5.8E-01 0.0337 3.9E-01 -0.0191 7.7E-01 0.0157 3.8E-01 eubacterium_hallii 2.7.2.1 acetate kinase 0.25 -0.0017 9.5E-01 9.6E-01 -0.0306 5.3E-01 -0.0015 9.6E-01 -0.0446 4.3E-01 -0.0238 1.2E-01 eubacterium_hallii 4.3.2.2 adenylosuccinate lyase 0.18 0.0145 5.6E-01 6.8E-01 -0.0400 4.2E-01 0.0573 7.8E-02 -0.0485 4.1E-01 0.0019 9.0E-01 eubacterium_hallii 6.3.4.2 ctp synthase (glutamine hydrolyzing) 0.22 0.0569 1.3E-02 1.8E-01 0.0625 1.5E-01 0.0110 7.1E-01 0.0224 6.6E-01 -0.0106 4.3E-01 eubacterium_hallii 6.3.2.6 phosphoribosylaminoimidazolesuccino 0.14 -0.0010 9.5E-01 9.6E-01 0.0438 1.9E-01 -0.0146 5.2E-01 -0.0215 5.8E-01 -0.0088 4.0E-01 carboxamide synthase eubacterium_hallii 6.3.3.1 phosphoribosylformylglycinamidine 0.19 0.0235 3.0E-01 4.6E-01 0.0047 9.1E-01 0.0092 7.5E-01 -0.0213 6.8E-01 0.0049 7.1E-01 cyclo-ligase eubacterium_hallii 2.7.8.5 cdp-diacylglycerol--glycerol-3- 0.34 -0.0091 1.4E-01 3.4E-01 0.0241 3.6E-02 -0.0067 4.0E-01 -0.0076 5.8E-01 0.0007 8.5E-01 phosphate 3-phosphatidyltransferase eubacterium_hallii 6.1.1.17 glutamate--trna ligase 0.12 -0.0014 9.2E-01 9.3E-01 0.0342 2.3E-01 0.0212 2.6E-01 0.0338 3.2E-01 -0.0006 9.5E-01 eubacterium_hallii 2.2.1.6 acetolactate synthase 0.18 -0.0133 4.5E-01 5.9E-01 -0.0060 8.6E-01 -0.0207 3.6E-01 -0.0250 5.2E-01 -0.0121 2.5E-01 eubacterium_hallii 6.3.5.5 carbamoyl-phosphate synthase 0.11 -0.0005 9.7E-01 9.7E-01 -0.0302 2.0E-01 -0.0153 3.4E-01 -0.0097 7.3E-01 -0.0059 4.3E-01 (glutamine-hydrolyzing) eubacterium_hallii 2.7.4.22 ump kinase 0.19 0.0458 1.2E-01 3.3E-01 -0.0866 1.1E-01 0.0632 8.8E-02 -0.0793 2.2E-01 0.0077 6.5E-01 eubacterium_hallii 6.1.1.1 tyrosine--trna ligase 0.11 0.0036 8.3E-01 8.8E-01 -0.0551 9.3E-02 0.0187 3.9E-01 -0.0399 3.1E-01 -0.0124 2.2E-01 eubacterium_hallii 6.3.4.21 nicotinate phosphoribosyltransferase 0.1 0.0059 6.8E-01 7.6E-01 -0.0708 7.3E-03 0.0159 3.8E-01 -0.0785 1.2E-02 -0.0085 3.1E-01 eubacterium_hallii 3.6.4.12 dna helicase 0.27 0.0168 1.8E-01 3.7E-01 -0.0038 8.7E-01 -0.0033 8.3E-01 -0.0046 8.7E-01 -0.0063 3.9E-01 eubacterium_hallii 5.3.1.9 glucose-6-phosphate Isomerase 0.34 -0.0167 6.6E-01 7.6E-01 0.0296 6.8E-01 0.0770 1.1E-01 0.0035 9.7E-01 -0.0100 6.6E-01 eubacterium_hallii 5.2.1.8 peptidylprolyl Isomerase 0.22 0.0209 3.7E-01 5.3E-01 -0.0222 6.1E-01 0.0169 5.6E-01 -0.0358 4.9E-01 -0.0059 6.6E-01 eubacterium_hallii 1.1.1.86 ketol-acid reductoisomerase (nadp(+)) 0.26 0.0076 8.0E-01 8.5E-01 0.0817 1.5E-01 0.0641 9.4E-02 -0.0434 5.1E-01 0.0010 9.6E-01

eubacterium_hallii 4.2.1.9 dihydroxy-acid dehydratase 0.11 0.0429 1.7E-03 1.3E-01 0.0170 5.1E-01 0.0342 4.8E-02 0.0083 7.8E-01 -0.0024 7.7E-01 eubacterium_hallii 2.4.1.18 1,4-alpha-glucan branching enzyme 0.23 0.0208 2.7E-01 4.4E-01 -0.0294 4.1E-01 -0.0030 9.0E-01 -0.0572 1.8E-01 -0.0086 4.5E-01 eubacterium_hallii 2.7.4.25 (d)cmp kinase 0.17 0.0076 8.1E-01 8.6E-01 -0.0114 8.5E-01 0.0426 2.9E-01 -0.1277 7.7E-02 -0.0102 5.9E-01 eubacterium_hallii 2.7.7.60 2-c-methyl-d-erythritol 4-phosphate 0.18 0.0125 5.7E-01 6.9E-01 -0.0819 3.7E-02 0.0185 5.1E-01 -0.0535 2.7E-01 -0.0187 1.5E-01 cytidylyltransferase eubacterium_hallii 1.1.1.25 shikimate dehydrogenase 0.2 0.0067 6.9E-01 7.7E-01 0.0251 4.4E-01 0.0165 4.5E-01 -0.0166 6.7E-01 -0.0029 7.8E-01 eubacterium_hallii 2.5.1.78 6,7-dimethyl-8-ribityllumazine 0.17 0.0271 3.6E-01 5.2E-01 0.0234 6.8E-01 -0.0265 4.9E-01 -0.0471 4.8E-01 -0.0022 9.0E-01 synthase eubacterium_hallii 4.1.2.4 deoxyribose-phosphate aldolase 0.13 -0.0051 8.0E-01 8.5E-01 -0.0086 8.2E-01 0.0028 9.1E-01 0.0504 2.5E-01 -0.0026 8.2E-01 eubacterium_hallii 1.2.99.2 carbon-monoxide dehydrogenase 0.3 0.0353 2.0E-01 3.9E-01 0.0753 1.5E-01 0.0632 7.2E-02 -0.0599 3.2E-01 -0.0008 9.6E-01 (acceptor) eubacterium_hallii 5.99.1.3 dna topoisomerase (atp-hydrolyzing) 0.27 0.0208 2.9E-01 4.6E-01 0.0158 6.9E-01 0.0352 1.7E-01 -0.0244 6.0E-01 0.0122 3.1E-01 eubacterium_hallii 1.1.1.17 mannitol-1-phosphate 5- 0.22 0.0107 5.9E-01 7.0E-01 0.0005 9.9E-01 0.0198 4.3E-01 0.0355 4.2E-01 0.0088 4.5E-01 dehydrogenase eubacterium_hallii 2.6.1.16 glutamine--fructose-6-phosphate 0.46 0.0741 4.5E-02 2.6E-01 0.1008 1.4E-01 0.0709 1.3E-01 -0.0841 3.0E-01 -0.0058 7.9E-01 transaminase (isomerizing) roseburia_hominis 4.2.3.3 methylglyoxal synthase 0.25 0.0862 5.5E-03 1.8E-01 0.0270 6.4E-01 0.0674 8.7E-02 0.1103 1.1E-01 0.0228 2.2E-01 roseburia_hominis 2.1.1.297 peptide chain release factor n(5)- 0.16 0.0560 7.2E-02 2.8E-01 -0.0355 5.2E-01 -0.0105 7.9E-01 -0.0793 2.6E-01 0.0042 8.2E-01 glutamine methyltransferase roseburia_hominis 2.1.1.192 23s rrna (adenine(2503)-c(2))- 0.17 0.0684 2.8E-02 2.2E-01 0.0111 8.4E-01 -0.0217 5.8E-01 -0.0314 6.4E-01 0.0086 6.4E-01 methyltransferase roseburia_hominis 3.2.2.27 uracil-dna glycosylase 0.18 0.0359 3.5E-01 5.1E-01 -0.1394 4.8E-02 -0.0295 5.5E-01 -0.1089 2.0E-01 -0.0198 3.8E-01 roseburia_hominis 1.17.1.8 4-hydroxy-tetrahydrodipicolinate 0.15 0.0137 6.1E-01 7.1E-01 -0.0375 4.4E-01 0.0189 5.8E-01 -0.0572 3.3E-01 0.0148 3.5E-01 reductase roseburia_hominis 2.7.7.6 dna-directed rna polymerase 0.49 0.1754 1.0E-02 1.8E-01 0.0011 9.9E-01 -0.0140 8.7E-01 0.0046 9.8E-01 -0.0355 3.7E-01 roseburia_hominis 2.1.1.182 16s rrna (adenine(1518)- 0.15 0.0500 1.0E-01 3.2E-01 0.0145 8.0E-01 0.0313 4.2E-01 -0.0533 4.3E-01 0.0198 2.7E-01 n(6)/adenine(1519)-n(6))- dimethyltransferase roseburia_hominis 5.99.1.3 dna topoisomerase (atp-hydrolyzing) 0.18 0.0486 1.1E-01 3.3E-01 -0.0550 3.4E-01 -0.0137 7.2E-01 -0.0252 7.1E-01 -0.0075 6.8E-01 roseburia_hominis 6.1.1.17 glutamate--trna ligase 0.22 0.0607 7.6E-02 2.9E-01 -0.0711 2.6E-01 -0.0457 2.9E-01 -0.0841 2.7E-01 -0.0152 4.4E-01 roseburia_hominis 2.7.1.90 diphosphate--fructose-6-phosphate 1- 0.12 0.0266 3.2E-01 4.8E-01 -0.0450 3.6E-01 -0.0045 9.0E-01 -0.0694 2.3E-01 -0.0126 4.2E-01 phosphotransferase roseburia_hominis 2.7.7.3 pantetheine-phosphate 0.17 0.0745 2.8E-02 2.2E-01 -0.0199 7.5E-01 -0.0061 8.9E-01 -0.0584 4.4E-01 -0.0298 1.4E-01 adenylyltransferase roseburia_hominis 2.7.7.2 fad synthetase 0.12 0.0513 2.1E-02 2.0E-01 0.0205 6.2E-01 -0.0062 8.3E-01 -0.0411 4.0E-01 -0.0169 2.0E-01 roseburia_hominis 4.1.2.4 deoxyribose-phosphate aldolase 0.21 0.0389 3.4E-01 5.0E-01 -0.0203 7.9E-01 -0.0156 7.6E-01 -0.1395 1.2E-01 -0.0504 3.6E-02 roseburia_hominis 1.2.1.41 glutamate-5-semialdehyde 0.14 0.0327 1.5E-01 3.5E-01 -0.0248 5.6E-01 -0.0255 3.8E-01 -0.0468 3.5E-01 0.0032 8.1E-01 dehydrogenase roseburia_hominis 5.3.1.12 glucuronate Isomerase 0.27 0.1051 1.8E-02 2.0E-01 -0.0482 5.6E-01 0.0481 3.9E-01 0.0031 9.8E-01 -0.0078 7.7E-01 roseburia_hominis 3.6.3.14 h(+)-transporting two-sector atpase 0.61 0.1657 7.8E-03 1.8E-01 0.0740 5.2E-01 0.0182 8.2E-01 -0.0750 6.0E-01 -0.0201 5.8E-01 roseburia_hominis 3.6.1.3 adenosinetriphosphatase 0.14 0.0529 7.2E-02 2.8E-01 -0.0107 8.4E-01 -0.0269 4.7E-01 -0.0628 3.3E-01 -0.0149 3.8E-01 roseburia_hominis 1.7.99.1 hydroxylamine reductase 0.23 0.0706 1.9E-02 2.0E-01 -0.0606 2.8E-01 -0.0220 5.6E-01 -0.0301 6.5E-01 -0.0174 3.2E-01 roseburia_hominis 5.3.1.23 s-methyl-5-thioribose-1-phosphate 0.16 0.0641 2.0E-02 2.0E-01 -0.0361 4.8E-01 -0.0255 4.7E-01 -0.0537 3.7E-01 -0.0060 7.1E-01 Isomerase roseburia_hominis 5.2.1.8 peptidylprolyl Isomerase 0.51 0.1586 3.1E-02 2.2E-01 -0.0094 9.5E-01 0.0070 9.4E-01 -0.1727 3.0E-01 -0.0597 1.6E-01 roseburia_hominis 2.4.2.9 uracil phosphoribosyltransferase 0.23 0.0719 9.7E-02 3.2E-01 -0.0572 4.8E-01 -0.0131 8.1E-01 -0.0381 6.9E-01 -0.0026 9.2E-01 70

Supplementary Data 4b Enzyme Detectio Plasma TMAO Choline Choline Red meat Red meat Species Enzyme Name ID n Rate Effect P FDR Effect P Effect P Effect P Effect P roseburia_hominis 2.6.1.42 branched-chain-amino-acid 0.22 0.0648 5.7E-02 2.6E-01 0.0366 5.7E-01 0.0050 9.1E-01 -0.1302 8.7E-02 -0.0497 1.5E-02 transaminase roseburia_hominis 2.7.1.40 pyruvate kinase 0.32 0.0254 5.4E-01 6.6E-01 0.0067 9.3E-01 0.0131 8.0E-01 0.0025 9.8E-01 -0.0073 7.6E-01 roseburia_hominis 2.7.2.8 acetylglutamate kinase 0.12 0.0223 3.3E-01 4.9E-01 -0.0422 3.3E-01 0.0004 9.9E-01 0.0228 6.6E-01 -0.0121 3.7E-01 roseburia_hominis 1.5.1.2 pyrroline-5-carboxylate reductase 0.24 0.1059 2.4E-02 2.1E-01 0.0261 7.6E-01 0.0013 9.8E-01 -0.1460 1.6E-01 -0.0199 4.6E-01 roseburia_hominis 2.5.1.16 spermidine synthase 0.14 0.0379 1.1E-01 3.3E-01 0.0254 5.6E-01 0.0047 8.8E-01 -0.0908 8.1E-02 -0.0183 2.0E-01 roseburia_hominis 1.1.1.25 shikimate dehydrogenase 0.23 0.0446 2.5E-01 4.3E-01 -0.0824 2.5E-01 -0.0244 6.2E-01 -0.0645 4.4E-01 -0.0194 3.9E-01 roseburia_hominis 3.5.4.2 adenine deaminase 0.26 0.0741 5.6E-02 2.6E-01 -0.0367 6.0E-01 0.0404 4.1E-01 -0.0357 6.8E-01 -0.0085 7.1E-01 roseburia_hominis 2.7.1.95 kanamycin kinase 0.25 0.0541 1.4E-01 3.3E-01 0.0190 7.8E-01 0.0316 4.9E-01 0.0906 2.6E-01 -0.0047 8.2E-01 roseburia_hominis 6.3.4.4 adenylosuccinate synthase 0.26 0.0502 9.7E-02 3.2E-01 -0.0531 3.4E-01 0.0072 8.5E-01 -0.0801 2.3E-01 -0.0258 1.5E-01 roseburia_hominis 2.7.7.87 l-threonylcarbamoyladenylate synthase 0.17 0.0787 1.6E-02 1.9E-01 -0.0181 7.5E-01 -0.0405 3.2E-01 -0.1041 1.6E-01 -0.0022 9.1E-01

roseburia_hominis 3.6.5.n1 elongation factor 4 0.15 0.0257 3.0E-01 4.6E-01 -0.0781 7.7E-02 -0.0038 9.0E-01 -0.0208 7.0E-01 0.0032 8.3E-01 roseburia_hominis 2.7.7.27 glucose-1-phosphate 0.53 0.2035 6.0E-03 1.8E-01 -0.0515 7.1E-01 -0.1143 2.1E-01 -0.1055 5.2E-01 -0.1121 8.6E-03 adenylyltransferase roseburia_hominis 2.4.2.22 xanthine phosphoribosyltransferase 0.2 0.0446 3.1E-01 4.7E-01 0.0088 9.2E-01 0.0101 8.6E-01 -0.0693 4.9E-01 -0.0229 3.8E-01 roseburia_hominis 2.4.99.17 s-adenosylmethionine:trna 0.13 0.0529 8.6E-02 3.0E-01 -0.0272 6.4E-01 0.0247 5.3E-01 -0.0348 6.2E-01 0.0150 4.1E-01 ribosyltransferase-isomerase roseburia_hominis 2.3.1.234 n(6)-l-threonylcarbamoyladenine 0.2 0.0219 5.1E-01 6.4E-01 0.0021 9.7E-01 0.0275 5.2E-01 -0.0425 5.7E-01 -0.0089 6.5E-01 synthase roseburia_hominis 2.7.1.6 galactokinase 0.2 0.0638 2.3E-02 2.0E-01 -0.0480 3.4E-01 -0.0046 9.0E-01 -0.0337 5.9E-01 -0.0227 1.7E-01 roseburia_hominis 2.1.2.3 phosphoribosylaminoimidazolecarboxa 0.19 0.0452 1.1E-01 3.3E-01 0.0119 8.1E-01 0.0115 7.5E-01 -0.0368 5.6E-01 0.0173 3.0E-01 mide formyltransferase roseburia_hominis 2.7.2.1 acetate kinase 0.28 0.0868 3.8E-02 2.5E-01 -0.0589 4.5E-01 0.0256 6.3E-01 -0.1916 3.7E-02 -0.0239 3.3E-01 roseburia_hominis 1.1.1.23 histidinol dehydrogenase 0.18 0.1130 6.3E-04 9.0E-02 -0.0223 7.3E-01 -0.0122 7.7E-01 -0.0529 4.9E-01 -0.0037 8.5E-01 roseburia_hominis 4.2.3.4 3-dehydroquinate synthase 0.12 0.0158 6.4E-01 7.4E-01 -0.1173 5.6E-02 -0.0602 1.5E-01 -0.0347 6.4E-01 -0.0162 4.0E-01 roseburia_hominis 2.5.1.54 3-deoxy-7-phosphoheptulonate 0.24 0.0413 2.1E-01 4.0E-01 -0.0543 3.7E-01 0.0353 3.9E-01 0.0064 9.3E-01 0.0146 4.5E-01 synthase roseburia_hominis 2.3.1.9 acetyl-coa c-acetyltransferase 0.5 0.2530 2.7E-03 1.6E-01 0.0300 8.5E-01 0.0072 9.5E-01 -0.1480 4.5E-01 -0.0457 3.5E-01 roseburia_hominis 6.3.4.3 formate--tetrahydrofolate ligase 0.23 0.0766 5.3E-02 2.6E-01 -0.0646 3.9E-01 -0.0026 9.6E-01 -0.0847 3.4E-01 -0.0218 3.4E-01 roseburia_hominis 2.7.7.24 glucose-1-phosphate 0.2 0.0104 7.9E-01 8.5E-01 -0.0403 5.8E-01 -0.0172 7.1E-01 0.0059 9.5E-01 0.0104 6.4E-01 thymidylyltransferase roseburia_hominis 6.3.2.4 d-alanine--d-alanine ligase 0.13 0.0553 6.8E-02 2.8E-01 -0.0461 4.0E-01 0.0160 6.7E-01 0.0612 3.6E-01 0.0202 2.5E-01 roseburia_hominis 2.1.2.9 methionyl-trna formyltransferase 0.21 0.0721 5.1E-02 2.6E-01 -0.0078 9.1E-01 0.0603 1.9E-01 -0.1338 1.1E-01 -0.0416 5.4E-02 roseburia_hominis 2.7.1.148 4-(cytidine 5'-diphospho)-2-c-methyl-d- 0.14 0.1018 5.8E-04 9.0E-02 0.0255 6.4E-01 0.0249 5.1E-01 -0.0403 5.4E-01 -0.0142 4.2E-01 erythritol kinase roseburia_hominis 2.4.2.17 atp phosphoribosyltransferase 0.11 0.0312 1.9E-01 3.9E-01 -0.0171 7.0E-01 0.0371 2.2E-01 -0.0342 5.1E-01 -0.0037 7.9E-01 roseburia_hominis 5.3.1.4 l-arabinose Isomerase 0.39 0.0592 2.2E-01 4.1E-01 -0.0117 9.0E-01 -0.0564 3.6E-01 -0.0022 9.8E-01 -0.0013 9.6E-01 roseburia_hominis 2.3.1.8 phosphate acetyltransferase 0.34 0.1008 4.2E-02 2.5E-01 -0.0060 9.5E-01 0.0472 4.5E-01 -0.0052 9.6E-01 -0.0086 7.7E-01 roseburia_hominis 6.1.1.20 phenylalanine--trna ligase 0.12 0.0269 3.2E-01 4.7E-01 -0.0903 6.2E-02 -0.0024 9.4E-01 -0.0288 6.2E-01 -0.0089 5.7E-01 roseburia_hominis 1.5.1.20 methylenetetrahydrofolate reductase 0.13 0.0517 3.0E-02 2.2E-01 -0.0632 1.6E-01 -0.0051 8.7E-01 -0.0408 4.5E-01 -0.0054 7.1E-01 (nad(p)h) roseburia_hominis 3.6.1.19 nucleoside-triphosphate diphosphatase 0.11 0.0199 4.0E-01 5.5E-01 -0.0239 6.0E-01 -0.0145 6.3E-01 -0.0323 5.5E-01 0.0019 8.9E-01

roseburia_hominis 4.2.1.8 mannonate dehydratase 0.31 0.0456 1.4E-01 3.4E-01 0.0154 7.9E-01 -0.0070 8.6E-01 -0.0586 4.0E-01 -0.0054 7.7E-01 roseburia_hominis 2.1.1.193 16s rrna (uracil(1498)-n(3))- 0.11 0.0228 1.2E-01 3.3E-01 0.0155 5.7E-01 0.0033 8.6E-01 -0.0211 5.1E-01 -0.0038 6.6E-01 methyltransferase roseburia_hominis 2.1.2.2 phosphoribosylglycinamide 0.13 0.0447 1.3E-01 3.3E-01 -0.0572 2.9E-01 -0.0187 6.2E-01 -0.0687 2.8E-01 -0.0168 3.3E-01 formyltransferase roseburia_hominis 2.5.1.47 cysteine synthase 0.26 0.0319 4.9E-01 6.2E-01 -0.0505 5.4E-01 -0.0078 8.9E-01 -0.0749 4.6E-01 -0.0046 8.6E-01 roseburia_hominis 6.3.2.8 udp-n-acetylmuramate--l-alanine 0.12 0.0126 5.8E-01 6.9E-01 -0.0033 9.4E-01 -0.0218 4.5E-01 -0.0448 3.6E-01 -0.0036 7.9E-01 ligase roseburia_hominis 3.4.23.36 signal peptidase II 0.17 0.0268 4.7E-01 6.1E-01 -0.0389 5.7E-01 -0.0290 5.4E-01 -0.0443 5.9E-01 -0.0278 2.0E-01 roseburia_hominis 3.6.1.1 Inorganic diphosphatase 0.15 0.0185 3.7E-01 5.3E-01 -0.0264 4.8E-01 -0.0115 6.6E-01 0.0134 7.6E-01 -0.0031 8.0E-01 roseburia_hominis 5.3.1.17 5-dehydro-4-deoxy-d-glucuronate 0.2 0.0282 4.4E-01 5.8E-01 -0.0853 2.1E-01 -0.0208 6.5E-01 -0.1088 1.8E-01 -0.0162 4.5E-01 Isomerase roseburia_hominis 3.1.1.11 pectinesterase 0.14 -0.0055 8.0E-01 8.5E-01 -0.0414 3.0E-01 0.0070 8.0E-01 -0.0005 9.9E-01 0.0091 4.7E-01 roseburia_hominis 3.5.99.6 glucosamine-6-phosphate deaminase 0.17 0.0507 2.1E-02 2.0E-01 0.0547 1.8E-01 -0.0071 8.0E-01 -0.0304 5.3E-01 0.0097 4.5E-01 roseburia_hominis 1.17.7.3 (e)-4-hydroxy-3-methylbut-2-enyl- 0.15 0.0677 5.7E-02 2.6E-01 -0.0840 2.1E-01 -0.0865 5.0E-02 -0.0267 7.4E-01 0.0067 7.4E-01 diphosphate synthase (flavodoxin) roseburia_hominis 2.1.1.72 site-specific dna-methyltransferase 0.16 -0.0088 6.1E-01 7.1E-01 -0.0282 3.7E-01 -0.0100 6.4E-01 0.0356 3.4E-01 -0.0026 7.7E-01 (adenine-specific) roseburia_hominis 2.8.4.3 trna-2-methylthio-n(6)- 0.14 0.0449 5.4E-02 2.6E-01 0.0611 1.6E-01 0.0118 6.9E-01 0.0191 7.1E-01 0.0023 8.7E-01 dimethylallyladenosine synthase roseburia_hominis 3.4.11.4 tripeptide aminopeptidase 0.14 0.0395 5.0E-02 2.6E-01 -0.0245 5.0E-01 -0.0245 3.4E-01 -0.0518 2.4E-01 0.0031 7.9E-01 roseburia_hominis 3.1.11.6 exodeoxyribonuclease vii 0.18 0.0464 1.5E-01 3.5E-01 -0.0490 4.2E-01 -0.0183 6.5E-01 -0.0253 7.2E-01 0.0044 8.2E-01 roseburia_hominis 2.3.1.30 serine o-acetyltransferase 0.12 0.0204 4.4E-01 5.8E-01 -0.0295 5.6E-01 -0.0701 4.3E-02 -0.0449 4.6E-01 -0.0029 8.5E-01 roseburia_hominis 4.1.1.49 phosphoenolpyruvate carboxykinase 0.66 0.1132 4.2E-02 2.5E-01 -0.0225 8.3E-01 0.0306 6.6E-01 -0.0656 6.0E-01 -0.0278 3.9E-01 (atp) roseburia_hominis 6.3.2.6 phosphoribosylaminoimidazolesuccino 0.2 0.0877 1.6E-02 1.9E-01 -0.0282 6.8E-01 0.0412 3.7E-01 -0.0309 7.1E-01 0.0045 8.3E-01 carboxamide synthase roseburia_hominis 6.1.1.1 tyrosine--trna ligase 0.13 0.0415 7.4E-02 2.8E-01 0.0087 8.4E-01 0.0212 4.7E-01 -0.0448 3.9E-01 -0.0086 5.3E-01 71

roseburia_hominis 4.1.1.23 orotidine-5'-phosphate decarboxylase 0.12 0.0635 8.8E-03 1.8E-01 -0.0070 8.8E-01 -0.0253 4.1E-01 -0.0059 9.1E-01 -0.0121 4.0E-01 roseburia_hominis 6.1.1.12 aspartate--trna ligase 0.32 0.0749 2.6E-02 2.1E-01 -0.0047 9.4E-01 0.0017 9.7E-01 -0.1160 1.2E-01 -0.0174 3.8E-01 roseburia_hominis 6.1.1.3 threonine--trna ligase 0.26 0.0743 2.6E-02 2.2E-01 0.0114 8.5E-01 0.0162 7.0E-01 -0.0396 5.9E-01 0.0061 7.5E-01 roseburia_hominis 2.1.1.228 trna (guanine(37)-n(1))- 0.16 0.0523 3.9E-02 2.5E-01 -0.0468 3.2E-01 0.0022 9.5E-01 -0.0705 2.2E-01 0.0105 4.8E-01 methyltransferase roseburia_hominis 2.5.1.72 quinolinate synthase 0.18 0.0382 2.6E-01 4.4E-01 0.0008 9.9E-01 -0.0187 6.6E-01 -0.0043 9.6E-01 -0.0021 9.2E-01 roseburia_hominis 1.1.1.85 3-isopropylmalate dehydrogenase 0.18 0.0569 8.3E-02 2.9E-01 -0.0094 8.8E-01 0.0323 4.3E-01 -0.0701 3.3E-01 -0.0072 7.1E-01 roseburia_hominis 2.1.2.1 glycine hydroxymethyltransferase 0.19 0.0555 9.8E-02 3.2E-01 0.0219 7.3E-01 -0.0253 5.5E-01 -0.1145 1.3E-01 0.0041 8.3E-01 roseburia_hominis 2.4.2.29 trna-guanine(34) transglycosylase 0.16 0.0189 5.0E-01 6.3E-01 -0.0478 3.5E-01 0.0151 6.7E-01 -0.0426 4.9E-01 -0.0127 4.4E-01 roseburia_hominis 4.3.2.2 adenylosuccinate lyase 0.3 0.0416 2.4E-01 4.3E-01 -0.1011 1.2E-01 -0.0102 8.2E-01 -0.1240 1.1E-01 -0.0083 6.9E-01 roseburia_hominis 2.7.1.11 6-phosphofructokinase 0.36 0.1364 7.4E-03 1.8E-01 0.0644 5.0E-01 -0.0220 7.3E-01 -0.0684 5.5E-01 -0.0309 3.0E-01 roseburia_hominis 3.5.1.25 n-acetylglucosamine-6-phosphate 0.11 0.0465 1.0E-02 1.8E-01 -0.0200 5.4E-01 -0.0032 8.9E-01 -0.0313 4.4E-01 -0.0001 9.9E-01 deacetylase roseburia_hominis 6.3.4.5 argininosuccinate synthase 0.2 0.0818 3.1E-02 2.2E-01 -0.0358 6.1E-01 -0.0596 2.2E-01 -0.0749 3.7E-01 -0.0292 1.9E-01 roseburia_hominis 2.6.1.9 histidinol-phosphate transaminase 0.16 0.0606 2.0E-02 2.0E-01 -0.0422 3.9E-01 0.0083 8.0E-01 -0.0202 7.3E-01 -0.0036 8.1E-01 roseburia_hominis 2.3.1.51 1-acylglycerol-3-phosphate o- 0.15 0.0710 1.4E-02 1.8E-01 0.0694 2.0E-01 0.0116 7.5E-01 -0.0047 9.4E-01 -0.0102 5.5E-01 acyltransferase roseburia_hominis 2.7.2.4 aspartate kinase 0.19 0.0709 2.5E-02 2.1E-01 -0.0179 7.6E-01 0.0182 6.5E-01 -0.0213 7.6E-01 0.0034 8.5E-01 roseburia_hominis 1.1.1.3 homoserine dehydrogenase 0.17 0.0635 6.0E-02 2.7E-01 -0.1518 1.5E-02 -0.0398 3.4E-01 -0.0618 4.1E-01 -0.0138 4.8E-01 roseburia_hominis 5.4.99.18 5-(carboxyamino)imidazole 0.12 0.0442 1.9E-01 3.8E-01 0.0893 1.5E-01 0.0350 4.0E-01 0.0049 9.5E-01 0.0011 9.5E-01 ribonucleotide mutase roseburia_hominis 2.6.1.52 phosphoserine transaminase 0.28 0.0823 1.1E-01 3.3E-01 -0.0567 5.6E-01 -0.0641 3.2E-01 -0.0731 5.3E-01 -0.0097 7.5E-01 roseburia_hominis 2.7.1.33 pantothenate kinase 0.15 0.0371 2.1E-01 4.0E-01 -0.0297 5.8E-01 -0.0909 1.3E-02 -0.0171 7.9E-01 -0.0064 7.1E-01 roseburia_hominis 2.4.1.227 acetylglucosaminyltransferase 0.19 0.0764 4.8E-02 2.6E-01 0.0060 9.3E-01 -0.0171 7.2E-01 0.0080 9.3E-01 -0.0255 2.5E-01 roseburia_hominis 5.1.1.3 glutamate racemase 0.11 0.0443 3.9E-02 2.5E-01 0.0133 7.3E-01 -0.0126 6.4E-01 -0.0347 4.6E-01 0.0043 7.3E-01 roseburia_hominis 2.2.1.2 transaldolase 0.29 0.0758 1.4E-01 3.3E-01 -0.0583 5.3E-01 -0.0124 8.4E-01 -0.0432 7.0E-01 -0.0142 6.3E-01 roseburia_hominis 2.5.1.7 udp-n-acetylglucosamine 1- 0.18 0.0309 3.6E-01 5.2E-01 -0.0937 1.3E-01 -0.0547 2.0E-01 -0.0164 8.3E-01 0.0011 9.6E-01 carboxyvinyltransferase roseburia_hominis 5.4.2.12 phosphoglycerate mutase (2,3- 0.31 0.1197 1.6E-02 1.9E-01 0.0227 8.1E-01 0.0109 8.6E-01 -0.0612 5.8E-01 0.0017 9.5E-01 diphosphoglycerate-independent) roseburia_hominis 6.1.1.6 lysine--trna ligase 0.48 0.0961 2.1E-02 2.0E-01 -0.0385 6.2E-01 0.0384 4.6E-01 0.0342 7.1E-01 0.0119 6.2E-01 roseburia_hominis 4.3.2.1 argininosuccinate lyase 0.17 0.0567 6.2E-02 2.7E-01 -0.0023 9.7E-01 -0.0234 5.4E-01 -0.0413 5.5E-01 -0.0299 9.6E-02 roseburia_hominis 3.4.21.88 repressor lexa 0.23 0.1202 1.1E-02 1.8E-01 -0.0046 9.6E-01 0.0374 5.4E-01 -0.0661 5.3E-01 0.0253 3.7E-01 roseburia_hominis 2.7.13.3 histidine kinase 0.22 0.0142 6.3E-02 2.7E-01 -0.0019 9.0E-01 -0.0021 8.3E-01 0.0000 1.0E+00 -0.0012 7.9E-01 roseburia_hominis 1.1.1.86 ketol-acid reductoisomerase (nadp(+)) 0.51 0.0981 1.2E-01 3.3E-01 0.0145 9.0E-01 0.0449 5.7E-01 -0.1163 4.0E-01 -0.0357 3.3E-01

roseburia_hominis 3.1.26.11 ribonuclease z 0.2 0.0446 1.9E-01 3.8E-01 -0.0877 1.5E-01 -0.0632 1.4E-01 -0.1055 1.6E-01 -0.0218 2.8E-01 roseburia_hominis 6.3.2.10 udp-n-acetylmuramoyl-tripeptide--d- 0.12 0.0104 6.7E-01 7.6E-01 -0.0508 2.6E-01 -0.0724 2.2E-02 -0.0194 7.2E-01 -0.0190 1.9E-01 alanyl-d-alanine ligase roseburia_hominis 2.7.8.13 phospho-n-acetylmuramoyl- 0.16 0.0742 1.4E-02 1.8E-01 0.0398 4.6E-01 0.0238 5.3E-01 0.0302 6.5E-01 0.0020 9.1E-01 pentapeptide-transferase roseburia_hominis 3.5.1.44 protein-glutamine glutaminase 0.15 0.0758 8.6E-03 1.8E-01 -0.0591 2.9E-01 0.0102 7.8E-01 -0.0031 9.6E-01 -0.0019 9.2E-01 roseburia_hominis 1.17.1.2 4-hydroxy-3-methylbut-2-enyl 0.29 0.1017 4.7E-02 2.6E-01 -0.0846 3.7E-01 -0.0611 3.5E-01 -0.1992 7.4E-02 -0.0626 3.8E-02 diphosphate reductase roseburia_hominis 6.1.1.15 proline--trna ligase 0.26 0.0957 1.1E-02 1.8E-01 -0.0173 8.1E-01 -0.0060 9.0E-01 -0.0888 2.9E-01 -0.0112 6.1E-01 72

Supplementary Data 4b Enzyme Detectio Plasma TMAO Choline Choline Red meat Red meat Species Enzyme Name ID n Rate Effect P FDR Effect P Effect P Effect P Effect P roseburia_hominis 4.2.1.10 3-dehydroquinate dehydratase 0.13 0.0092 7.4E-01 8.0E-01 -0.0011 9.8E-01 0.0122 7.3E-01 0.0203 7.4E-01 -0.0193 2.4E-01 roseburia_hominis 6.1.1.14 glycine--trna ligase 0.42 0.0713 6.4E-02 2.7E-01 -0.0476 5.1E-01 0.0377 4.4E-01 -0.0857 3.1E-01 -0.0287 2.0E-01 roseburia_hominis 2.4.1.25 4-alpha-glucanotransferase 0.18 0.0502 1.3E-01 3.3E-01 -0.1219 4.7E-02 -0.0287 4.9E-01 -0.1018 1.7E-01 0.0058 7.7E-01 roseburia_hominis 3.4.21.89 signal peptidase I 0.11 0.0194 3.4E-01 5.0E-01 0.0218 5.6E-01 0.0108 6.7E-01 0.0462 3.0E-01 -0.0041 7.2E-01 roseburia_hominis 6.3.4.13 phosphoribosylamine--glycine ligase 0.17 0.0886 3.5E-03 1.8E-01 -0.0621 2.8E-01 0.0118 7.6E-01 -0.0141 8.3E-01 0.0181 3.2E-01 roseburia_hominis 2.4.1.21 starch synthase 0.38 0.1099 1.0E-02 1.8E-01 0.0797 3.2E-01 0.0715 1.9E-01 0.0331 7.3E-01 0.0076 7.7E-01 roseburia_hominis 2.7.1.30 glycerol kinase 0.59 0.3203 1.6E-03 1.3E-01 0.1683 3.8E-01 -0.0751 5.6E-01 0.0095 9.7E-01 -0.0111 8.5E-01 roseburia_hominis 2.6.1.83 ll-diaminopimelate aminotransferase 0.2 0.0971 6.1E-03 1.8E-01 -0.0267 6.8E-01 -0.0173 7.0E-01 -0.1610 4.5E-02 -0.0105 6.1E-01 roseburia_hominis 3.5.1.88 peptide deformylase 0.19 0.0280 4.5E-01 5.9E-01 0.0158 8.1E-01 0.0082 8.6E-01 -0.0515 5.3E-01 -0.0091 6.8E-01 roseburia_hominis 5.1.3.11 cellobiose epimerase 0.11 0.0743 1.1E-03 1.0E-01 0.0148 7.3E-01 0.0067 8.2E-01 0.0287 5.7E-01 0.0058 6.7E-01 roseburia_hominis 3.1.26.3 ribonuclease III 0.12 0.0194 2.9E-01 4.5E-01 -0.0505 1.3E-01 -0.0041 8.6E-01 0.0093 8.2E-01 -0.0009 9.3E-01 roseburia_hominis 2.2.1.6 acetolactate synthase 0.31 0.0548 1.0E-01 3.2E-01 -0.0459 4.6E-01 0.0138 7.5E-01 0.0079 9.2E-01 -0.0038 8.5E-01 roseburia_hominis 6.3.3.1 phosphoribosylformylglycinamidine 0.18 0.0360 2.5E-01 4.3E-01 -0.0254 6.6E-01 -0.0168 6.7E-01 -0.1245 7.0E-02 -0.0341 6.1E-02 cyclo-ligase roseburia_hominis 2.7.2.11 glutamate 5-kinase 0.16 0.0664 2.3E-02 2.0E-01 -0.0313 5.7E-01 -0.0128 7.3E-01 -0.0236 7.2E-01 0.0026 8.8E-01 roseburia_hominis 2.4.1.281 4-o-beta-d-mannosyl-d-glucose 0.12 0.0429 8.3E-02 2.9E-01 -0.0173 7.1E-01 -0.0207 5.1E-01 -0.0345 5.2E-01 0.0020 8.9E-01 phosphorylase roseburia_hominis 2.7.8.5 cdp-diacylglycerol--glycerol-3- 0.25 -0.0001 9.9E-01 9.9E-01 0.0076 4.0E-01 0.0015 8.1E-01 -0.0068 5.2E-01 -0.0006 8.3E-01 phosphate 3-phosphatidyltransferase roseburia_hominis 2.5.1.75 trna dimethylallyltransferase 0.1 0.0038 8.5E-01 8.9E-01 0.0214 5.6E-01 -0.0018 9.4E-01 0.0391 3.6E-01 0.0053 6.4E-01 roseburia_hominis 1.1.1.42 Isocitrate dehydrogenase (nadp(+)) 0.23 0.0879 8.6E-03 1.8E-01 -0.0112 8.5E-01 0.0252 5.5E-01 -0.0301 6.8E-01 0.0174 3.8E-01 roseburia_hominis 1.4.1.13 glutamate synthase (nadph) 0.22 0.0819 3.5E-02 2.4E-01 0.0101 8.9E-01 0.0166 7.3E-01 0.0588 5.0E-01 0.0068 7.6E-01 roseburia_hominis 2.3.1.n2 phosphate acyltransferase 0.27 0.0961 3.0E-02 2.2E-01 0.0645 4.4E-01 -0.0474 4.0E-01 -0.1950 5.2E-02 -0.0069 7.9E-01 roseburia_hominis 2.5.1.19 3-phosphoshikimate 1- 0.13 0.0486 7.9E-02 2.9E-01 -0.1011 6.8E-02 -0.0113 7.5E-01 -0.0271 6.6E-01 -0.0149 3.7E-01 carboxyvinyltransferase roseburia_hominis 6.1.1.19 arginine--trna ligase 0.25 0.0755 2.7E-02 2.2E-01 -0.0821 2.0E-01 -0.0414 3.3E-01 -0.0296 7.0E-01 -0.0155 4.4E-01 roseburia_hominis 5.4.2.7 phosphopentomutase 0.21 0.0547 1.8E-01 3.8E-01 -0.1084 1.6E-01 -0.0270 6.0E-01 0.0372 6.8E-01 -0.0229 3.4E-01 roseburia_hominis 2.4.2.10 orotate phosphoribosyltransferase 0.16 0.0587 5.3E-02 2.6E-01 -0.0210 7.0E-01 -0.0179 6.4E-01 0.0104 8.8E-01 0.0094 5.9E-01 roseburia_hominis 4.2.1.11 phosphopyruvate hydratase 0.18 0.0557 1.6E-01 3.6E-01 -0.0477 5.2E-01 -0.0611 2.2E-01 -0.0474 6.0E-01 0.0213 3.6E-01 roseburia_hominis 4.2.1.46 dtdp-glucose 4,6-dehydratase 0.34 0.0611 2.7E-01 4.4E-01 0.0044 9.7E-01 -0.0319 6.5E-01 -0.0534 6.7E-01 -0.0642 4.6E-02 roseburia_hominis 1.1.1.94 glycerol-3-phosphate dehydrogenase 0.2 0.0819 1.2E-02 1.8E-01 -0.0152 8.0E-01 0.0430 3.0E-01 -0.1355 5.9E-02 -0.0102 5.9E-01 (nad(p)(+)) roseburia_hominis 3.4.21.92 endopeptidase clp 0.19 0.0880 4.3E-02 2.6E-01 0.0145 8.6E-01 0.0609 2.7E-01 -0.0678 4.8E-01 0.0076 7.7E-01 roseburia_hominis 1.4.1.14 glutamate synthase (nadh) 0.22 0.0819 3.5E-02 2.4E-01 0.0101 8.9E-01 0.0166 7.3E-01 0.0588 5.0E-01 0.0068 7.6E-01 roseburia_hominis 2.1.2.11 3-methyl-2-oxobutanoate 0.11 0.0328 2.4E-01 4.3E-01 -0.0783 1.3E-01 -0.0282 4.2E-01 -0.0143 8.1E-01 -0.0142 3.9E-01 hydroxymethyltransferase roseburia_hominis 2.7.4.8 guanylate kinase 0.24 0.0703 1.2E-01 3.3E-01 0.0258 7.5E-01 -0.0150 7.9E-01 -0.1027 3.0E-01 -0.0053 8.4E-01 roseburia_hominis 3.5.2.3 dihydroorotase 0.2 0.0387 2.7E-01 4.4E-01 -0.0818 2.1E-01 -0.0168 7.1E-01 -0.0805 3.0E-01 0.0006 9.8E-01 roseburia_hominis 4.1.1.20 diaminopimelate decarboxylase 0.12 0.0162 4.8E-01 6.1E-01 0.0174 6.8E-01 -0.0046 8.7E-01 -0.0158 7.5E-01 -0.0121 3.7E-01 roseburia_hominis 2.1.1.198 16s rrna (cytidine(1402)-2'-o)- 0.14 0.0078 7.7E-01 8.3E-01 0.0277 5.7E-01 -0.0177 6.0E-01 -0.0757 1.9E-01 -0.0094 5.5E-01 methyltransferase roseburia_hominis 2.7.1.23 nad(+) kinase 0.14 0.0610 5.2E-02 2.6E-01 -0.0763 1.9E-01 -0.0007 9.9E-01 0.0887 2.0E-01 0.0109 5.5E-01 roseburia_hominis 2.8.4.4 [ribosomal protein s12] (aspartate(89)- 0.17 0.0793 4.4E-03 1.8E-01 -0.0456 3.7E-01 0.0053 8.8E-01 -0.0947 1.4E-01 -0.0213 1.9E-01 c(3))-methylthiotransferase

roseburia_hominis 2.7.1.48 uridine kinase 0.2 0.0994 6.5E-03 1.8E-01 -0.0517 4.5E-01 0.0156 7.4E-01 0.0179 8.2E-01 -0.0170 4.3E-01 roseburia_hominis 2.2.1.7 1-deoxy-d-xylulose-5-phosphate 0.2 0.0397 1.0E-01 3.2E-01 -0.0353 4.3E-01 -0.0508 9.5E-02 -0.0971 7.2E-02 -0.0229 1.1E-01 synthase roseburia_hominis 1.1.1.267 1-deoxy-d-xylulose-5-phosphate 0.12 0.0456 8.4E-02 2.9E-01 -0.0494 3.1E-01 -0.0070 8.3E-01 -0.0387 5.1E-01 -0.0083 5.9E-01 reductoisomerase roseburia_hominis 3.1.26.5 ribonuclease p 0.22 0.0901 5.0E-02 2.6E-01 0.0635 4.5E-01 0.0207 7.2E-01 -0.0872 3.9E-01 -0.0066 8.1E-01 roseburia_hominis 3.1.1.61 protein-glutamate methylesterase 0.32 0.1354 1.0E-02 1.8E-01 0.0003 1.0E+00 0.0583 3.8E-01 0.0129 9.1E-01 0.0266 3.9E-01 roseburia_hominis 2.7.4.3 adenylate kinase 0.26 0.0781 1.1E-01 3.3E-01 0.0538 5.5E-01 0.0353 5.6E-01 -0.1277 2.3E-01 -0.0015 9.6E-01 roseburia_hominis 2.8.1.4 trna sulfurtransferase 0.18 0.0261 4.0E-01 5.5E-01 -0.0188 7.4E-01 0.0256 5.1E-01 -0.0579 4.0E-01 -0.0011 9.5E-01 roseburia_hominis 1.3.99.2 transferred entry: 1.3.8.1 0.52 0.1524 6.1E-02 2.7E-01 0.0498 7.4E-01 -0.0246 8.1E-01 -0.1239 4.9E-01 -0.0422 3.7E-01 roseburia_hominis 4.3.3.7 4-hydroxy-tetrahydrodipicolinate 0.22 0.0699 1.0E-01 3.2E-01 -0.0018 9.8E-01 -0.0591 2.7E-01 -0.1611 8.0E-02 -0.0278 2.6E-01 synthase roseburia_hominis 5.3.1.9 glucose-6-phosphate Isomerase 0.3 0.1354 5.9E-03 1.8E-01 -0.0536 5.6E-01 -0.0090 8.8E-01 -0.1130 3.1E-01 0.0170 5.6E-01 roseburia_hominis 2.1.3.2 aspartate carbamoyltransferase 0.19 0.0529 1.4E-01 3.4E-01 -0.0041 9.5E-01 0.0134 7.6E-01 0.0051 9.5E-01 -0.0054 7.9E-01 roseburia_hominis 2.4.2.1 purine-nucleoside phosphorylase 0.2 0.0865 2.7E-02 2.2E-01 0.0063 9.3E-01 0.0181 7.1E-01 -0.0976 2.6E-01 0.0110 6.3E-01 roseburia_hominis 5.4.99.12 trna pseudouridine(38-40) synthase 0.12 0.0153 3.7E-01 5.3E-01 -0.0178 5.8E-01 -0.0196 3.8E-01 0.0016 9.7E-01 0.0070 5.0E-01 roseburia_hominis 4.2.1.47 gdp-mannose 4,6-dehydratase 0.2 0.0837 3.9E-02 2.5E-01 -0.0695 3.5E-01 -0.0476 3.5E-01 0.0339 7.0E-01 0.0248 2.9E-01 roseburia_hominis 2.1.1.199 16s rrna (cytosine(1402)-n(4))- 0.28 0.0875 2.1E-02 2.0E-01 -0.0030 9.7E-01 0.0014 9.8E-01 -0.0711 4.1E-01 -0.0130 5.5E-01 methyltransferase roseburia_hominis 2.5.1.9 riboflavin synthase 0.12 0.0276 6.7E-02 2.7E-01 -0.0482 8.5E-02 0.0079 6.8E-01 -0.0316 3.4E-01 -0.0142 1.1E-01 roseburia_hominis 6.3.4.21 nicotinate phosphoribosyltransferase 0.18 0.0569 9.0E-02 3.1E-01 -0.1073 8.5E-02 -0.0186 6.7E-01 -0.0397 5.9E-01 -0.0184 3.6E-01 roseburia_hominis 6.1.1.22 asparagine--trna ligase 0.29 0.0457 2.9E-01 4.5E-01 -0.0272 7.3E-01 -0.0314 5.6E-01 -0.0483 6.1E-01 0.0166 5.1E-01 roseburia_hominis 6.3.1.1 aspartate--ammonia ligase 0.19 0.0533 1.1E-01 3.3E-01 0.0125 8.4E-01 -0.0613 1.4E-01 -0.0466 5.4E-01 -0.0215 2.7E-01 roseburia_hominis 1.1.1.271 gdp-l-fucose synthase 0.12 0.0485 1.6E-01 3.5E-01 -0.0300 6.4E-01 -0.0008 9.9E-01 0.0081 9.2E-01 -0.0114 5.7E-01 roseburia_hominis 2.8.1.7 cysteine desulfurase 0.27 0.0456 2.1E-01 4.0E-01 -0.0685 3.0E-01 0.0129 7.8E-01 -0.0189 8.1E-01 0.0049 8.2E-01 roseburia_hominis 5.1.3.3 aldose 1-epimerase 0.43 0.0877 1.2E-01 3.3E-01 -0.0350 7.4E-01 -0.0583 4.2E-01 0.0141 9.1E-01 -0.0169 6.1E-01 roseburia_hominis 1.1.1.58 tagaturonate reductase 0.19 0.0334 2.7E-01 4.4E-01 -0.0171 7.7E-01 -0.0382 3.3E-01 -0.0204 7.6E-01 -0.0101 5.8E-01 73

Supplementary Data 5a Supplementary Data 5a. Association of functional pathways (metagenomics) within TMAO-associated species with plasma TMAO levels, and intakes of choline and red meat. Full model was adjusted for age, BMI, physical activity, energy intake, smoking, cumulative dietary quality (since 1986), antibiotics use, probiotics use, the Bristol Stool Chart, and/or fish intake (for non-fish dietary variables). Choline intake- Choline intake- Red meat Red meat Pathway Detection Plasma TMAO Species Pathway ID Pathway Name FFQ 7DDR intake-FFQ intake-7DDR type Rate Effect P FDR Effect P Effect P Effect P Effect P Alistipes shahii PWY_6609328814 Pathway adenine and adenosine salvage III 0.7 0.000962 2.5E-02 3.0E-02 -0.000449 5.7E-01 -0.000176 7.3E-01 -0.000060 9.3E-01 -0.000751 8.4E-02 Alistipes shahii PWY_7219328814 Pathway adenosine ribonucleotides de novo biosynthesis 0.7 0.001291 1.4E-03 3.4E-03 -0.000584 4.3E-01 -0.000300 5.3E-01 -0.000165 7.9E-01 -0.000820 4.5E-02 Alistipes shahii PWY_5695328814 Pathway urate biosynthesis/inosine 5'-phosphate degradation 0.74 0.001411 3.7E-04 1.7E-03 -0.000391 6.0E-01 -0.000207 6.6E-01 -0.000002 1.0E+00 -0.000801 4.7E-02 Alistipes shahii PYRIDNUCSYN328814 Pathway nad biosynthesis I (from aspartate) 0.75 0.001161 3.2E-03 5.3E-03 -0.000340 6.4E-01 -0.000234 6.2E-01 -0.000360 5.7E-01 -0.000562 1.6E-01 Alistipes shahii PWY_1042328814 Pathway glycolysis Iv (plant cytosol) 0.71 0.001770 1.1E-04 1.2E-03 -0.000783 3.6E-01 -0.000183 7.4E-01 -0.000319 6.6E-01 -0.000389 4.0E-01 Alistipes shahii PWY_1269328814 Pathway cmp-3-deoxy-d-manno-octulosonate biosynthesis I 0.72 0.001353 6.8E-04 2.2E-03 -0.000143 8.4E-01 -0.000649 1.7E-01 -0.000245 6.9E-01 -0.000267 5.1E-01 Alistipes shahii NONOXIPENT328814 Pathway pentose phosphate pathway (non-oxidative branch) 0.66 0.001008 1.2E-02 1.6E-02 -0.000337 6.4E-01 -0.000728 1.3E-01 -0.000222 7.2E-01 -0.000746 6.8E-02 Alistipes shahii PWY_6163328814 Pathway chorismate biosynthesis from 3-dehydroquinate 0.62 0.001245 1.8E-03 3.5E-03 -0.000497 4.9E-01 -0.000206 6.6E-01 -0.000195 7.5E-01 -0.000510 2.1E-01 Alistipes shahii ANAGLYCOLYSIS328814 Pathway glycolysis III (from glucose) 0.68 0.001346 1.8E-03 3.5E-03 -0.000717 3.7E-01 -0.000346 5.0E-01 -0.000123 8.6E-01 -0.000326 4.6E-01 Alistipes shahii PWY_5659328814 Pathway gdp-mannose biosynthesis 0.74 0.001224 1.6E-03 3.5E-03 -0.000559 4.4E-01 -0.000313 5.0E-01 -0.000462 4.5E-01 -0.000450 2.5E-01 Alistipes shahii DTDPRHAMSYN328814 Pathway dtdp-l-rhamnose biosynthesis I 0.73 0.001443 2.9E-04 1.6E-03 -0.000526 4.8E-01 -0.000311 5.1E-01 0.000030 9.6E-01 -0.000268 5.1E-01 Alistipes shahii HISDEG328814 Pathway l-histidine degradation I 0.74 0.000968 6.6E-03 9.0E-03 -0.000325 6.3E-01 -0.000143 7.4E-01 -0.000509 3.7E-01 -0.000349 3.4E-01 Alistipes shahii GALACTUROCAT328814 Pathway d-galacturonate degradation I 0.71 0.001056 3.5E-03 5.7E-03 -0.000988 1.4E-01 -0.000069 8.7E-01 -0.000324 5.7E-01 -0.000530 1.5E-01 Alistipes shahii PWY_7221328814 Pathway guanosine ribonucleotides de novo biosynthesis 0.7 0.001324 8.8E-04 2.6E-03 -0.000264 7.2E-01 -0.000421 3.7E-01 -0.000032 9.6E-01 -0.000512 2.1E-01 Clostridiales bacterium 1 7 47FAA PWY0_1297457421 SuperP purine deoxyribonucleosides degradation 0.12 0.000646 2.3E-02 2.8E-02 -0.000067 8.9E-01 -0.000058 8.6E-01 0.000388 3.1E-01 0.000437 1.3E-01 Clostridiales bacterium 1 7 47FAA PWY_7219457421 Pathway adenosine ribonucleotides de novo biosynthesis 0.11 0.000291 3.6E-03 5.7E-03 0.000067 6.8E-01 0.000029 8.1E-01 0.000185 1.6E-01 0.000202 4.7E-02 Clostridiales bacterium 1 7 47FAA PWY0_1296457421 Pathway purine ribonucleosides degradation 0.13 0.000385 1.6E-03 3.5E-03 -0.000066 7.5E-01 -0.000091 5.3E-01 0.000120 4.7E-01 0.000112 3.7E-01 Clostridiales bacterium 1 7 47FAA PWY_6609457421 Pathway adenine and adenosine salvage III 0.13 0.000255 4.0E-02 4.5E-02 -0.000088 6.7E-01 -0.000051 7.3E-01 0.000121 4.7E-01 0.000085 5.0E-01 Clostridiales bacterium 1 7 47FAA PWY_7220457421 Pathway adenosine deoxyribonucleotides de novo biosynthesis II 0.12 0.000287 5.3E-04 2.0E-03 -0.000015 9.1E-01 0.000044 6.5E-01 0.000145 2.0E-01 0.000198 2.0E-02 Clostridiales bacterium 1 7 47FAA PWY_7111457421 Pathway pyruvate fermentation to Isobutanol (engineered) 0.16 0.000200 7.0E-02 7.5E-02 -0.000162 3.9E-01 -0.000026 8.4E-01 0.000120 4.4E-01 0.000073 5.2E-01 Clostridiales bacterium 1 7 47FAA PWY_7222457421 Pathway guanosine deoxyribonucleotides de novo biosynthesis II 0.12 0.000287 5.3E-04 2.0E-03 -0.000015 9.1E-01 0.000044 6.5E-01 0.000145 2.0E-01 0.000198 2.0E-02 Clostridiales bacterium 1 7 47FAA VALSYN457421 Pathway l-valine biosynthesis 0.1 0.000179 2.8E-02 3.4E-02 -0.000056 6.8E-01 -0.000019 8.4E-01 0.000087 4.4E-01 0.000060 4.7E-01 Clostridium clostridioforme PWY_72191531 Pathway adenosine ribonucleotides de novo biosynthesis 0.1 0.000294 1.3E-02 1.6E-02 -0.000062 7.8E-01 -0.000003 9.8E-01 0.000132 4.8E-01 -0.000035 7.7E-01 Clostridium nexile PWY_627729361 SuperP 5-aminoimidazole ribonucleotide biosynthesis 0.1 -0.001481 2.3E-03 4.3E-03 -0.000162 8.5E-01 0.000475 4.1E-01 0.000964 1.9E-01 -0.000110 8.2E-01 Clostridium nexile PWY_673729361 Pathway starch degradation v 0.11 -0.000574 1.7E-03 3.5E-03 0.000164 6.3E-01 0.000116 5.9E-01 0.000351 2.2E-01 -0.000050 7.9E-01 Clostridium nexile PWY_711129361 Pathway pyruvate fermentation to Isobutanol (engineered) 0.12 -0.000529 3.0E-03 5.0E-03 -0.000035 9.2E-01 0.000016 9.4E-01 0.000237 3.9E-01 -0.000205 2.5E-01 Clostridium nexile PWY_721929361 Pathway adenosine ribonucleotides de novo biosynthesis 0.12 -0.000761 9.3E-05 1.2E-03 0.000145 6.9E-01 0.000027 9.1E-01 0.000362 2.3E-01 -0.000076 7.0E-01 Clostridium nexile PWY_612229361 Pathway 5-aminoimidazole ribonucleotide biosynthesis II 0.1 -0.000559 2.5E-03 4.5E-03 -0.000020 9.5E-01 0.000164 4.5E-01 0.000365 1.9E-01 -0.000039 8.3E-01 Clostridium nexile VALSYN29361 Pathway l-valine biosynthesis 0.11 -0.000564 1.1E-03 2.8E-03 -0.000015 9.6E-01 0.000019 9.3E-01 0.000249 3.5E-01 -0.000179 3.0E-01 Eubacterium biforme PWY_62771735 SuperP 5-aminoimidazole ribonucleotide biosynthesis 0.23 -0.002747 6.9E-04 2.2E-03 -0.001062 4.9E-01 -0.000457 6.3E-01 -0.001916 1.6E-01 0.001605 4.6E-02 Eubacterium biforme THRESYN1735 SuperP l-threonine biosynthesis 0.18 -0.001103 6.9E-02 7.5E-02 -0.000884 4.2E-01 0.000131 8.5E-01 -0.000698 4.6E-01 0.001903 1.7E-03 Eubacterium biforme DTDPRHAMSYN1735 Pathway dtdp-l-rhamnose biosynthesis I 0.19 -0.000747 5.1E-04 2.0E-03 -0.000288 4.7E-01 -0.000400 1.1E-01 -0.000169 6.2E-01 0.000535 1.4E-02 Eubacterium biforme PWY0_12961735 Pathway purine ribonucleosides degradation 0.22 -0.000613 3.3E-02 3.9E-02 -0.000219 6.9E-01 -0.000061 8.6E-01 -0.000523 2.8E-01 0.000955 8.5E-04 Eubacterium biforme PWY_73571735 Pathway thiamin formation from pyrithiamine and oxythiamine 0.12 -0.000646 1.4E-03 3.4E-03 -0.000361 3.5E-01 -0.000258 2.8E-01 -0.000708 3.2E-02 0.000229 2.6E-01 (yeast) Eubacterium biforme PWY_56861735 Pathway ump biosynthesis 0.21 -0.000874 6.2E-03 8.8E-03 -0.000317 6.0E-01 -0.000071 8.5E-01 -0.000557 2.9E-01 0.000875 6.0E-03 Eubacterium biforme COA_11735 Pathway coenzyme a biosynthesis II (mammalian) 0.17 -0.000364 1.3E-01 1.4E-01 0.000114 8.0E-01 0.000131 6.4E-01 -0.000186 6.2E-01 0.000700 3.9E-03 Eubacterium biforme GLYCOGENSYNTH1735 Pathway glycogen biosynthesis I (from adp-d-glucose) 0.22 -0.000733 6.5E-03 9.0E-03 -0.000345 5.0E-01 -0.000060 8.5E-01 -0.000567 2.1E-01 0.000726 7.1E-03 Eubacterium biforme PWY_72191735 Pathway adenosine ribonucleotides de novo biosynthesis 0.24 -0.000980 3.6E-03 5.7E-03 -0.000078 9.0E-01 -0.000033 9.3E-01 -0.000635 2.7E-01 0.000915 6.3E-03 Eubacterium biforme PWY_63861735 Pathway udp-n-acetylmuramoyl-pentapeptide biosynthesis II 0.14 -0.000274 1.6E-01 1.6E-01 -0.000292 4.0E-01 -0.000131 5.7E-01 -0.000373 2.0E-01 0.000442 2.3E-02 (lysine-containing) Eubacterium biforme PWY66_4221735 Pathway d-galactose degradation v (leloir pathway) 0.22 -0.000762 9.2E-03 1.2E-02 -0.000567 3.1E-01 -0.000269 4.3E-01 -0.000523 2.9E-01 0.000599 4.1E-02 Eubacterium biforme PWY_66091735 Pathway adenine and adenosine salvage III 0.22 -0.000613 3.7E-02 4.2E-02 -0.000267 6.3E-01 0.000032 9.2E-01 -0.000572 2.4E-01 0.000883 2.7E-03 Eubacterium biforme PEPTIDOGLYCANSYN1735 Pathway peptidoglycan biosynthesis I (meso-diaminopimelate 0.14 -0.000306 1.1E-01 1.2E-01 -0.000220 5.2E-01 -0.000076 7.4E-01 -0.000339 2.4E-01 0.000484 1.2E-02 containing) Eubacterium biforme ARO1735 Pathway chorismate biosynthesis I 0.12 -0.000298 1.7E-01 1.7E-01 -0.000252 5.4E-01 0.000223 3.8E-01 0.000009 9.8E-01 0.000499 2.1E-02 Eubacterium biforme PWY_67371735 Pathway starch degradation v 0.22 -0.000528 3.5E-02 4.0E-02 -0.000471 3.2E-01 -0.000139 6.3E-01 -0.000448 2.9E-01 0.000762 2.4E-03 Eubacterium biforme PWY_51001735 Pathway pyruvate fermentation to acetate and lactate II 0.23 -0.000815 9.7E-03 1.3E-02 -0.000363 5.5E-01 -0.000176 6.3E-01 -0.000627 2.4E-01 0.000695 2.7E-02 Eubacterium biforme PWY_61221735 Pathway 5-aminoimidazole ribonucleotide biosynthesis II 0.23 -0.001078 5.6E-04 2.0E-03 -0.000334 5.8E-01 -0.000152 6.8E-01 -0.000666 2.1E-01 0.000679 2.9E-02 Eubacterium biforme PWY_61511735 Pathway s-adenosyl-l-methionine cycle I 0.23 -0.000932 4.7E-03 7.0E-03 -0.000655 3.0E-01 -0.000272 4.8E-01 -0.000815 1.4E-01 0.000755 2.2E-02 Eubacterium biforme PWY_63871735 Pathway udp-n-acetylmuramoyl-pentapeptide biosynthesis I (meso- 0.14 -0.000261 1.6E-01 1.7E-01 -0.000299 3.7E-01 -0.000134 5.5E-01 -0.000361 2.0E-01 0.000431 2.3E-02 diaminopimelate containing) Eubacterium biforme PWY_61211735 Pathway 5-aminoimidazole ribonucleotide biosynthesis I 0.22 -0.001094 8.0E-04 2.5E-03 -0.000187 7.6E-01 -0.000141 7.1E-01 -0.000626 2.5E-01 0.000740 2.3E-02 Eubacterium biforme PWY_61631735 Pathway chorismate biosynthesis from 3-dehydroquinate 0.12 -0.000310 1.3E-01 1.4E-01 -0.000314 4.2E-01 0.000258 2.8E-01 -0.000026 9.4E-01 0.000436 3.5E-02 Eubacterium biforme PWY_69361735 Pathway seleno-amino acid biosynthesis 0.2 -0.000577 4.5E-02 4.9E-02 -0.000300 5.8E-01 -0.000230 5.0E-01 -0.000333 4.8E-01 0.000681 1.7E-02 Eubacterium hallii PWY_711139488 Pathway pyruvate fermentation to Isobutanol (engineered) 0.83 0.001272 4.3E-05 1.1E-03 0.000955 7.3E-02 0.000323 3.9E-01 0.000413 3.4E-01 0.000056 8.6E-01 75

Supplementary Data 5a Choline intake- Choline intake- Red meat Red meat Pathway Detection Plasma TMAO Species Pathway ID Pathway Name FFQ 7DDR intake-FFQ intake-7DDR type Rate Effect P FDR Effect P Effect P Effect P Effect P Eubacterium hallii COA_139488 Pathway coenzyme a biosynthesis II (mammalian) 0.51 0.000861 4.5E-03 6.9E-03 0.000559 2.7E-01 -0.000232 5.2E-01 -0.000022 9.6E-01 -0.000131 6.8E-01 Eubacterium hallii PWY_673739488 Pathway starch degradation v 0.69 0.000992 6.2E-03 8.8E-03 0.001094 8.3E-02 0.000089 8.4E-01 0.000473 3.6E-01 -0.000279 4.5E-01 Eubacterium hallii PWY0_131939488 Pathway cdp-diacylglycerol biosynthesis II 0.6 0.001068 1.8E-03 3.5E-03 0.000651 2.7E-01 0.000362 3.8E-01 -0.000319 5.1E-01 -0.000208 5.6E-01 Eubacterium hallii PWY_670339488 Pathway preq0 biosynthesis 0.61 0.001115 2.6E-03 4.5E-03 0.000576 3.6E-01 0.000120 7.9E-01 -0.000062 9.0E-01 -0.000405 2.9E-01 Eubacterium hallii PWY_566739488 Pathway cdp-diacylglycerol biosynthesis I 0.6 0.001068 1.8E-03 3.5E-03 0.000651 2.7E-01 0.000362 3.8E-01 -0.000319 5.1E-01 -0.000208 5.6E-01 Eubacterium hallii PANTO39488 Pathway phosphopantothenate biosynthesis I 0.82 0.001324 3.0E-04 1.6E-03 0.000588 3.6E-01 0.000332 4.5E-01 0.000177 7.3E-01 -0.000142 7.1E-01 Eubacterium hallii PWY_721939488 Pathway adenosine ribonucleotides de novo biosynthesis 0.87 0.001314 1.6E-04 1.5E-03 0.000762 2.0E-01 0.000035 9.3E-01 0.000300 5.3E-01 -0.000248 4.9E-01 Eubacterium hallii VALSYN39488 Pathway l-valine biosynthesis 0.83 0.001272 4.3E-05 1.1E-03 0.000955 7.3E-02 0.000323 3.9E-01 0.000413 3.4E-01 0.000056 8.6E-01 Eubacterium hallii PWY_722139488 Pathway guanosine ribonucleotides de novo biosynthesis 0.72 0.000675 3.1E-02 3.6E-02 0.000886 9.1E-02 0.000088 8.1E-01 0.000005 9.9E-01 -0.000152 6.4E-01 Eubacterium hallii PWY_616339488 Pathway chorismate biosynthesis from 3-dehydroquinate 0.64 0.001401 8.8E-05 1.2E-03 0.000622 3.1E-01 0.000093 8.3E-01 -0.000261 6.0E-01 -0.000315 3.9E-01 Eubacterium hallii PWY_670039488 Pathway queuosine biosynthesis 0.62 0.001523 2.0E-06 1.7E-04 0.000663 2.2E-01 0.000048 9.0E-01 0.000148 7.4E-01 0.000072 8.3E-01 Eubacterium hallii PWY_615139488 Pathway s-adenosyl-l-methionine cycle I 0.58 0.001109 2.3E-03 4.3E-03 0.000633 3.0E-01 0.000215 6.2E-01 -0.000090 8.6E-01 -0.000139 7.1E-01 Roseburia hominis PWY_6277301301 SuperP 5-aminoimidazole ribonucleotide biosynthesis 0.66 0.003278 3.2E-04 1.6E-03 -0.001427 3.5E-01 -0.001011 3.5E-01 -0.000469 7.0E-01 -0.001453 1.2E-01 Roseburia hominis COMPLETE_ARO301301 SuperP aromatic amino acid biosynthesis 0.43 0.002165 1.4E-02 1.7E-02 -0.000160 9.1E-01 -0.000860 4.1E-01 -0.000174 8.9E-01 -0.000836 3.5E-01 Roseburia hominis VALSYN301301 Pathway l-valine biosynthesis 0.69 0.001233 3.3E-04 1.6E-03 -0.000412 4.8E-01 -0.000244 5.5E-01 -0.000244 6.1E-01 -0.000397 2.6E-01 Roseburia hominis PEPTIDOGLYCANSYN301301 Pathway peptidoglycan biosynthesis I (meso-diaminopimelate 0.46 0.001119 4.3E-04 1.9E-03 -0.000048 9.3E-01 -0.000238 5.3E-01 0.000055 9.0E-01 -0.000200 5.4E-01 containing) Roseburia hominis ARO301301 Pathway chorismate biosynthesis I 0.45 0.000877 7.9E-03 1.1E-02 0.000058 9.2E-01 -0.000335 3.9E-01 -0.000067 8.8E-01 -0.000181 5.9E-01 Roseburia hominis PWY0_1296301301 Pathway purine ribonucleosides degradation 0.58 0.000949 2.1E-03 4.0E-03 -0.000325 5.4E-01 0.000012 9.7E-01 -0.000164 7.0E-01 -0.000288 3.6E-01 Roseburia hominis PWY_6122301301 Pathway 5-aminoimidazole ribonucleotide biosynthesis II 0.66 0.001214 1.8E-04 1.5E-03 -0.000401 4.7E-01 -0.000347 3.7E-01 -0.000218 6.2E-01 -0.000530 1.1E-01 Roseburia hominis PWY_6387301301 Pathway udp-n-acetylmuramoyl-pentapeptide biosynthesis I (meso- 0.48 0.001043 1.1E-03 2.8E-03 -0.000099 8.6E-01 -0.000267 4.8E-01 0.000045 9.2E-01 -0.000226 4.9E-01 diaminopimelate containing) Roseburia hominis PWY_7219301301 Pathway adenosine ribonucleotides de novo biosynthesis 0.82 0.001278 1.7E-03 3.5E-03 -0.000523 4.5E-01 -0.000389 4.2E-01 0.000018 9.7E-01 -0.000387 3.5E-01 Roseburia hominis PWY_6737301301 Pathway starch degradation v 0.72 0.001239 6.4E-04 2.2E-03 -0.000419 5.0E-01 -0.000465 2.8E-01 -0.000141 7.8E-01 -0.000270 4.7E-01 Roseburia hominis PANTO301301 Pathway phosphopantothenate biosynthesis I 0.64 0.001162 3.4E-04 1.6E-03 0.000077 8.9E-01 0.000099 8.0E-01 -0.000089 8.4E-01 -0.000134 6.9E-01 Roseburia hominis PWY_6386301301 Pathway udp-n-acetylmuramoyl-pentapeptide biosynthesis II 0.48 0.001070 9.9E-04 2.8E-03 -0.000117 8.3E-01 -0.000308 4.3E-01 0.000017 9.7E-01 -0.000235 4.8E-01 (lysine-containing) Roseburia hominis PWY_5686301301 Pathway ump biosynthesis 0.5 0.001373 9.6E-05 1.2E-03 -0.000640 2.9E-01 -0.000411 3.3E-01 -0.000400 4.1E-01 -0.000504 1.6E-01 Roseburia hominis PWY_6121301301 Pathway 5-aminoimidazole ribonucleotide biosynthesis I 0.56 0.001236 2.4E-04 1.6E-03 -0.000373 5.1E-01 -0.000268 5.0E-01 0.000051 9.1E-01 -0.000328 3.4E-01 Roseburia hominis PWY_5097301301 Pathway l-lysine biosynthesis vi 0.48 0.001155 2.9E-04 1.6E-03 -0.000395 4.7E-01 -0.000207 5.9E-01 -0.000126 7.8E-01 -0.000355 2.8E-01 Roseburia hominis NONMEVIPP301301 Pathway methylerythritol phosphate pathway I 0.42 0.000965 2.9E-03 5.0E-03 -0.000052 9.2E-01 -0.000113 7.7E-01 -0.000155 7.3E-01 -0.000236 4.8E-01 Roseburia hominis COA_1301301 Pathway coenzyme a biosynthesis II (mammalian) 0.44 0.000908 5.3E-03 7.8E-03 -0.000227 6.8E-01 -0.000015 9.7E-01 0.000196 6.6E-01 -0.000141 6.7E-01 Roseburia hominis PWY0_1319301301 Pathway cdp-diacylglycerol biosynthesis II 0.52 0.001014 1.1E-03 2.8E-03 -0.000052 9.2E-01 -0.000057 8.8E-01 -0.000093 8.3E-01 -0.000325 3.1E-01 Roseburia hominis PWY_5667301301 Pathway cdp-diacylglycerol biosynthesis I 0.52 0.001014 1.1E-03 2.8E-03 -0.000052 9.2E-01 -0.000057 8.8E-01 -0.000093 8.3E-01 -0.000325 3.1E-01 Roseburia hominis PWY_7357301301 Pathway thiamin formation from pyrithiamine and oxythiamine 0.53 0.001350 5.1E-05 1.1E-03 -0.000470 4.1E-01 -0.000282 4.8E-01 -0.000225 6.3E-01 -0.000515 1.3E-01 (yeast) Roseburia hominis PWY_6163301301 Pathway chorismate biosynthesis from 3-dehydroquinate 0.49 0.000922 4.9E-03 7.2E-03 -0.000142 8.0E-01 -0.000328 4.0E-01 -0.000232 6.1E-01 -0.000088 7.9E-01 Roseburia hominis PWY_5100301301 Pathway pyruvate fermentation to acetate and lactate II 0.64 0.001243 2.1E-04 1.6E-03 -0.000327 5.7E-01 0.000016 9.7E-01 0.000053 9.1E-01 -0.000191 5.8E-01

Supplementary Data 5b Supplementary Data 5b. Association of transcriptions of pathways (RNA/DNA ratio) within TMAO-associated species with plasma TMAO levels, and intakes of choline and red meat. Full model was adjusted for age, BMI, physical activity, energy intake, smoking, cumulative dietary quality (since 1986), antibiotics use, probiotics use, the Bristol Stool Chart, and/or fish intake (for non-fish dietary variables). Choline Choline Red meat Red meat Detection Plasma TMAO Species Pathway ID Pathway Name intake-FFQ intake-7DDR intake-FFQ intake-7DDR Rate Effect P FDR Effect P Effect P Effect P Effect P Alistipes shahii PWY_6609328814 adenine and adenosine salvage III 0.22 0.0511 5.0E-01 5.6E-01 0.1491 3.0E-01 -0.0108 9.1E-01 0.0073 9.7E-01 -0.0732 9.5E-02 Alistipes shahii NONOXIPENT328814 pentose phosphate pathway (non-oxidative branch) 0.22 0.0437 5.9E-01 6.2E-01 0.0177 9.1E-01 -0.0612 5.4E-01 -0.1782 3.3E-01 -0.0557 2.3E-01 Alistipes shahii PYRIDNUCSYN328814 nad biosynthesis I (from aspartate) 0.18 0.0654 2.2E-01 4.0E-01 0.0669 5.0E-01 -0.0622 3.5E-01 0.1494 2.2E-01 -0.0116 7.1E-01 Alistipes shahii PWY_5695328814 urate biosynthesis/inosine 5'-phosphate degradation 0.29 0.0863 2.6E-01 4.3E-01 0.0840 5.7E-01 -0.0251 7.9E-01 -0.0201 9.1E-01 -0.0169 7.0E-01 Alistipes shahii HISDEG328814 l-histidine degradation I 0.28 0.1831 6.3E-02 2.2E-01 0.1455 4.4E-01 0.0326 7.9E-01 -0.0202 9.3E-01 0.0106 8.5E-01 Alistipes shahii PWY_1042328814 glycolysis Iv (plant cytosol) 0.21 0.1394 3.5E-02 1.7E-01 0.1044 4.0E-01 -0.0092 9.1E-01 0.0083 9.6E-01 -0.0413 2.8E-01 Alistipes shahii PWY_1269328814 cmp-3-deoxy-d-manno-octulosonate biosynthesis I 0.26 0.0352 6.6E-01 6.6E-01 0.0908 5.5E-01 -0.0880 3.8E-01 -0.0517 7.8E-01 -0.0739 1.1E-01 Alistipes shahii PWY_6163328814 chorismate biosynthesis from 3-dehydroquinate 0.12 0.0538 3.9E-01 5.1E-01 0.0044 9.7E-01 -0.0843 2.8E-01 -0.0412 7.7E-01 -0.0173 6.4E-01 Alistipes shahii DTDPRHAMSYN328814 dtdp-l-rhamnose biosynthesis I 0.17 0.0783 1.2E-01 2.9E-01 0.0330 7.2E-01 -0.0297 6.4E-01 0.0454 6.8E-01 -0.0109 7.1E-01 Alistipes shahii ANAGLYCOLYSIS328814 glycolysis III (from glucose) 0.19 0.1628 2.9E-02 1.7E-01 -0.0093 9.5E-01 -0.0394 6.7E-01 -0.0085 9.6E-01 -0.0305 4.8E-01 Alistipes shahii PWY_7221328814 guanosine ribonucleotides de novo biosynthesis 0.15 0.0453 4.3E-01 5.1E-01 0.0264 8.1E-01 -0.0097 8.9E-01 0.0388 7.7E-01 -0.0065 8.4E-01 Alistipes shahii PWY_5659328814 gdp-mannose biosynthesis 0.27 0.0870 3.0E-01 4.6E-01 0.2058 1.9E-01 -0.0931 3.7E-01 -0.0052 9.8E-01 -0.0232 6.3E-01 Alistipes shahii GALACTUROCAT328814 d-galacturonate degradation I 0.16 -0.0468 4.4E-01 5.1E-01 0.0979 3.9E-01 -0.1165 1.2E-01 0.1464 2.8E-01 -0.0291 4.0E-01 Alistipes shahii PWY_7219328814 adenosine ribonucleotides de novo biosynthesis 0.16 0.0899 1.5E-01 3.4E-01 0.0358 7.6E-01 -0.1374 7.8E-02 0.0788 5.7E-01 -0.0373 3.0E-01 Eubacterium hallii PWY_721939488 adenosine ribonucleotides de novo biosynthesis 0.12 0.0824 6.7E-02 2.2E-01 -0.0056 9.5E-01 0.1171 3.8E-02 -0.0336 7.5E-01 -0.0099 7.1E-01 Roseburia hominis PWY_5100301301 pyruvate fermentation to acetate and lactate II 0.12 0.1261 2.8E-02 1.7E-01 -0.1059 3.3E-01 -0.0294 6.9E-01 -0.0469 7.1E-01 0.0326 3.4E-01 Roseburia hominis VALSYN301301 l-valine biosynthesis 0.17 0.1576 1.2E-02 1.7E-01 0.1600 1.7E-01 0.1527 5.3E-02 -0.1110 4.3E-01 -0.0121 7.4E-01 Roseburia hominis PWY_7219301301 adenosine ribonucleotides de novo biosynthesis 0.29 0.0635 4.1E-01 5.1E-01 0.0554 6.9E-01 0.0764 4.3E-01 -0.3560 3.1E-02 -0.0311 4.9E-01 Roseburia hominis PWY0_1296301301 purine ribonucleosides degradation 0.13 0.1090 8.6E-02 2.5E-01 -0.0409 7.3E-01 -0.0177 8.2E-01 -0.1619 2.6E-01 0.0117 7.5E-01 Roseburia hominis PWY_6737301301 starch degradation v 0.19 0.0891 2.0E-01 4.0E-01 -0.0704 5.8E-01 -0.0008 9.9E-01 -0.1157 4.5E-01 0.0138 7.3E-01

Li J, et al. Gut 2021;0:1–10. doi: 10.1136/gutjnl-2020-322473