Supplementary Table 8. Multivariate correlation between LacMan ratio and Fecal Microbiota

GLS, covariates controlled for, outliers > 6SD excluded Bacterial phylum P-value Coefficient of correlation 0.77 -1.60 x 10-2 Proteobacteria 0.04 0.83 Bacteroidetes 0.43 -0.04 Tenericutes 0.05 -7.12 Actinobacteria 1.61 x 10-3 0.47 Verrucomicrobia 0.16 -0.25 TM7 0.23 281.34 Euryarchaeota 0.89 0.26 Cyanobacteria 0.36 -5.43 Fusobacteria 0.28 162.06 Lentisphaerae 0.45 -33.99

Dichotomized model (Presence vs. Absence), covariates controlled for Bacterial phylum P-value Coefficient of correlation Firmicutes 1.00 0.00 Proteobacteria 1.00 0.00 Bacteroidetes 1.00 0.00 Tenericutes 0.80 0.00 Actinobacteria 1.00 0.00 Verrucomicrobia 0.79 -0.01 TM7 0.87 0.00 Euryarchaeota 0.83 0.00 Cyanobacteria 0.19 -0.02 Fusobacteria 0.25 0.03 Lentisphaerae 0.80 0.01 GLS, covariates controlled for, outliers > 6SD excluded Bacterial family P-value Coefficient of correlation Lachnospiraceae 0.47 0.05 Streptococcaceae 0.02 1.94 Ruminococcaceae 0.11 -0.14 Oxalobacteraceae 0.19 -320.84 Bacteroidaceae 0.88 -0.01 Enterobacteriaceae 0.02 1.53 Clostridiales Undefined Family 0.72 -0.07 Peptococcaceae 0.92 -1.13 RF39 Undefined Family 0.09 -8.12 Bifidobacteriaceae 0.16 0.34 Verrucomicrobiaceae 0.16 -0.25 Veillonellaceae 0.99 0.00 Peptostreptococcaceae 0.26 2.78 Coriobacteriaceae 4.70 x 10-3 0.73 Mogibacteriaceae 0.01 -30.37 Undefined Family 0.77 -2.36 Clostridiaceae 0.44 0.96 Supplementary Table 8. Multivariate correlation between LacMan ratio and Fecal Microbiota

Pasteurellaceae 0.67 1.29 Christensenellaceae 0.12 -1.80 Odoribacteraceae 0.78 -0.67 Turicibacteraceae 0.30 139.14 Erysipelotrichaceae 0.07 2.05 Alcaligenaceae 0.25 1.02 Prevotellaceae 0.42 -0.06 Paraprevotellaceae 0.99 0.01 Barnesiellaceae 0.24 1.28 Tissierellaceae 0.30 -16.30 Lactobacillaceae 0.26 -22.46 Leuconostocaceae 0.43 87.76 Porphyromonadaceae 0.44 0.56 Dehalobacteriaceae 0.14 -58.72 Rikenellaceae 0.52 -0.30 Carnobacteriaceae 0.90 -25.41 Campylobacteraceae 0.37 200.23 Lactobacillales Undefined Family 0.33 -93.89 Moraxellaceae 0.12 314.92 Gemellaceae 0.29 80.31 TM73 Undefined Family 0.23 281.34 Desulfovibrionaceae 0.56 -1.42 Corynebacteriaceae 0.03 705.66 Neisseriaceae 0.03 1832.46 Actinomycetaceae 0.33 18.81 RF32 Undefined Family 0.81 0.93 Eubacteriaceae 0.17 148.89 Micrococcaceae 0.96 -10.62 Methanobacteriaceae 0.89 0.26 YS2 Undefined Family 0.20 -7.82 Staphylococcaceae 0.42 545.81 Streptophyta Undefined Family 0.19 32.31 S247 Undefined Family 0.21 -7.68 ML615J28 Undefined Family 0.22 -9.74 Aerococcaceae 0.01 224.96 Fusobacteriaceae 0.28 162.06 Enterococcaceae 0.12 -83.46 Victivallaceae 0.45 -33.99 Weeksellaceae 0.81 -234.63 Burkholderiales Undefined Family 0.65 36.32 Flavobacteriaceae 0.44 -1015.01 SHA98 Undefined Family 0.08 -137.86 Aeromonadaceae 0.46 -773.21 EtOH8 0.30 -82.25

Supplementary Table 8. Multivariate correlation between LacMan ratio and Fecal Microbiota

Dichotomized model (Presence vs. Absence), covariates controlled for Bacterial family P-value Coefficient of correlation Lachnospiraceae 1.00 0.00 Streptococcaceae 1.00 0.00 Ruminococcaceae 1.00 0.00 Oxalobacteraceae 0.86 0.00 Bacteroidaceae 1.00 0.00 Enterobacteriaceae 0.35 -0.03 Clostridiales Undefined Family 1.00 0.00 Peptococcaceae 0.38 -0.01 RF39 Undefined Family 0.69 -0.01 Bifidobacteriaceae 1.00 0.00 Verrucomicrobiaceae 0.79 -0.01 Veillonellaceae 1.00 0.00 Peptostreptococcaceae 1.00 0.00 Coriobacteriaceae 1.00 0.00 Mogibacteriaceae 1.00 0.00 Bacilli Undefined Family 0.27 -0.02 Clostridiaceae 1.00 0.00 Pasteurellaceae 0.61 -0.01 Christensenellaceae 0.77 -0.01 Odoribacteraceae 0.10 -0.04 Turicibacteraceae 0.57 0.01 Erysipelotrichaceae 1.00 0.00 Alcaligenaceae 0.21 -0.04 Prevotellaceae 1.00 0.00 Paraprevotellaceae 0.47 0.01 Barnesiellaceae 0.15 0.03 Tissierellaceae 0.78 0.00 Lactobacillaceae 0.72 0.01 Leuconostocaceae 0.41 -0.01 Porphyromonadaceae 1.00 0.00 Dehalobacteriaceae 0.02 -0.04 Rikenellaceae 1.00 0.00 Carnobacteriaceae 0.98 0.00 Campylobacteraceae 0.38 0.02 Lactobacillales Undefined Family 0.76 -0.01 Moraxellaceae 0.69 -0.01 Gemellaceae 0.07 0.03 TM73 Undefined Family 0.87 0.00 Desulfovibrionaceae 0.69 -0.01 Corynebacteriaceae 0.21 0.02 Neisseriaceae 0.00 0.08 Actinomycetaceae 1.00 0.00 RF32 Undefined Family 0.72 -0.01 Eubacteriaceae 0.37 0.01 Micrococcaceae 0.28 -0.02 Supplementary Table 8. Multivariate correlation between LacMan ratio and Fecal Microbiota

Methanobacteriaceae 0.83 0.00 YS2 Undefined Family 0.85 0.00 Staphylococcaceae 0.25 0.03 Streptophyta Undefined Family 0.08 -0.03 S247 Undefined Family 0.48 0.01 ML615J28 Undefined Family 0.35 -0.02 Aerococcaceae 0.92 0.00 Fusobacteriaceae 0.25 0.03 Enterococcaceae 0.37 0.02 Victivallaceae 0.80 0.01 Weeksellaceae 0.71 -0.01 Burkholderiales Undefined Family 0.71 -0.01 Flavobacteriaceae 0.51 -0.02 SHA98 Undefined Family 0.42 -0.01 Aeromonadaceae 0.99 0.00 EtOH8 0.75 -0.01

GLS, covariates controlled for, outliers > 6SD excluded Bacterial Genus P-value Coefficient of correlation Dorea 0.89 -0.13 Ruminococcus 0.20 0.68 Streptococcus 0.03 1.97 Lachnospiraceae Undefined Genus 0.64 0.06 Ruminococcaceae Undefined Genus 0.20 -0.17 Oxalobacteraceae Undefined Genus 0.19 -320.84 Blautia 0.39 0.19 Bacteroides 0.88 -0.01 Enterobacteriaceae Undefined Genus 0.02 1.53 Clostridiales Undefined Genus 0.72 -0.07 Ruminococcus 0.23 -0.30 Roseburia 0.14 -0.58 Oscillospira 0.44 -0.76 Peptococcaceae Family, rc44 Genus 0.99 0.22 RF39 Undefined Genus 0.09 -8.12 Bifidobacterium 0.16 0.34 Coprococcus 0.17 0.62 Akkermansia 0.16 -0.25 Dialister 0.77 -0.09 Peptostreptococcaceae Undefined Genus 0.39 2.13 Coriobacteriaceae Undefined Genus 0.45 0.84 Mogibacteriaceae Undefined Genus 0.01 -30.08 Bacilli Undefined Genus 0.77 -2.36 Clostridiaceae Family, Clostridium genus 0.98 0.03 Haemophilus 0.39 2.65 Christensenellaceae Undefined Genus 0.12 -1.82 Faecalibacterium 0.69 -0.06 Supplementary Table 8. Multivariate correlation between LacMan ratio and Fecal Microbiota

Butyricimonas 0.24 -7.58 Clostridiaceae Family, SMB53 Genus 0.04 212.28 Veillonella 0.01 4.58 Lachnospira 0.01 2.84 0.30 139.14 Erysipelotrichaceae Undefined Genus 0.04 3.08 Eubacterium 0.90 0.29 Erysipelotrichaceae Family, Sutterella Genus 0.25 1.02 Prevotella 0.42 -0.06 Paraprevotella 0.99 0.01 Barnesiellaceae Undefined Genus 0.24 1.28 Phascolarctobacterium 0.37 -0.28 Clostridiaceae Undefined Genus 0.09 3.65 Finegoldia 0.72 -64.90 Megamonas 0.87 -0.11 Peptostreptococcus 0.30 213.08 Lactobacillus 0.26 -22.46 Weissella 0.05 488.04 Parvimonas 0.58 -47.37 Parabacteroides 0.45 0.55 Erysipelotrichaceae Family, cc 115 Genus 0.02 -85.43 Tissierellaceae Family, WAL 1855D Genus 0.45 -28.36 Adlercreutzia 0.56 -19.45 Peptoniphilus 0.47 -53.00 Collinsella 0.13 0.44 Dehalobacterium 0.14 -58.72 Eggerthella 0.33 868.27 Rikenellaceae Undefined Genus 0.52 -0.30 Mogibacterium 0.65 -100.28 Odoribacter 0.86 0.46 Granulicatella 0.59 208.24 Slackia 0.50 -4.65 Campylobacter 0.37 200.23 Lactobacillales Undefined Genus 0.33 -93.89 Erysipelotrichaceae Family, Clostridium Genus 0.56 -47.97 0.96 -18.01 Anaerotruncus 0.45 -23.94 Porphyromonas 0.72 -18.95 Leuconostoc 0.82 33.53 0.01 -43.56 Acinetobacter 0.31 209.87 Gemellaceae Undefined Genus 0.29 80.31 TM73 Undefined Genus 0.23 281.34 Oribacterium 0.60 340.30 0.83 -44.46 Christensenella 0.96 5.08 Lactococcus 0.78 -2.59 Supplementary Table 8. Multivariate correlation between LacMan ratio and Fecal Microbiota

Desulfovibrio 0.25 4.62 Carnobacteriaceae Undefined Genus 0.56 216.77 Peptococcus 0.04 225.77 Corynebacterium 0.03 705.66 Neisseria 0.19 1815.28 Serratia 0.21 2265.51 0.34 5.17 Anaerostipes 0.06 -6.22 Bifidobacteriaceae Undefined Genus 0.56 584.97 Actinomyces 0.26 23.71 Succiniclasticum 0.93 -0.14 Peptococcaceae Undefined Genus 0.65 -18.87 Lachnobacterium 0.26 -2.13 RF32 Undefined Genus 0.81 0.93 Anaerofustis 0.35 159.51 Varibaculum 0.83 40.88 Rothia 0.96 -10.62 Methanobrevibacter 0.89 0.26 YS2 Undefined Genus 0.20 -7.82 Staphylococcus 0.42 545.81 Streptophyta Undefined Genus 0.19 32.31 S247 Undefined Genus 0.21 -7.68 ML615J28 Undefined Genus 0.22 -9.74 Acidaminococcus 0.07 3.82 Aerococcaceae Undefined Genus 0.01 224.96 Actinobacillus 0.14 1538.88 Tissierellaceae Family, Genus ph2 0.97 7.22 Bilophila 0.12 -5.21 Anaerococcus 0.36 -116.49 Fusobacterium 0.28 162.06 Pseudobutyrivibrio 0.28 -52.56 Pseudoramibacter Eubacterium 0.69 90.19 Veillonellaceae Undefined Genus 0.95 12.61 Enterococcus 0.12 -83.46 Mobiluncus 0.85 -132.10 Victivallaceae Undefined Genus 0.45 -33.99 Chryseobacterium 0.81 -234.63 Burkholderiales Undefined Genus 0.65 36.32 Microvirgula 0.04 2637.64 Aggregatibacter 0.80 13.23 Megasphaera 0.06 4.87 Atopobium 0.29 282.04 Flavobacterium 0.44 -1015.01 Tissierellaceae Family, Genus 168 0.33 -184.78 Enhydrobacter 0.90 141.69 Scardovia 0.11 1016.43 SHA98 Undefined Genus 0.08 -137.86 Supplementary Table 8. Multivariate correlation between LacMan ratio and Fecal Microbiota

Actinomycetaceae Undefined Genus 0.75 -192.64 Aeromonadaceae Undefined Genus 0.46 -773.21 EtOH8 Undefined Genus 0.30 -82.25

Dichotomized model (Presence vs. Absence), covariates controlled for Bacterial Genus P-value Coefficient of correlation Dorea 1.00 0.00 Ruminococcus 1.00 0.00 Streptococcus 1.00 0.00 Lachnospiraceae Undefined Genus 1.00 0.00 Ruminococcaceae Undefined Genus 1.00 0.00 Oxalobacteraceae Undefined Genus 0.86 0.00 Blautia 1.00 0.00 Bacteroides 1.00 0.00 Enterobacteriaceae Undefined Genus 0.35 -0.03 Clostridiales Undefined Genus 1.00 0.00 Ruminococcus 1.00 0.00 Roseburia 1.00 0.00 Oscillospira 1.00 0.00 Peptococcaceae Family, rc44 Genus 0.10 -0.03 RF39 Undefined Genus 0.69 -0.01 Bifidobacterium 1.00 0.00 Coprococcus 1.00 0.00 Akkermansia 0.79 -0.01 Dialister 0.57 0.02 Peptostreptococcaceae Undefined Genus 1.00 0.00 Coriobacteriaceae Undefined Genus 1.00 0.00 Mogibacteriaceae Undefined Genus 1.00 0.00 Bacilli Undefined Genus 0.27 -0.02 Clostridiaceae Family, Clostridium genus 1.00 0.00 Haemophilus 0.41 -0.02 Christensenellaceae Undefined Genus 0.69 -0.01 Faecalibacterium 1.00 0.00 Butyricimonas 0.20 -0.02 Clostridiaceae Family, SMB53 Genus 0.47 -0.01 Veillonella 1.00 0.00 Lachnospira 1.00 0.00 Turicibacter 0.57 0.01 Erysipelotrichaceae Undefined Genus 1.00 0.00 Eubacterium 0.52 -0.02 Erysipelotrichaceae Family, Sutterella Genus 0.21 -0.04 Prevotella 1.00 0.00 Paraprevotella 0.47 0.01 Barnesiellaceae Undefined Genus 0.15 0.03 Phascolarctobacterium 0.95 0.00 Clostridiaceae Undefined Genus 1.00 0.00 Supplementary Table 8. Multivariate correlation between LacMan ratio and Fecal Microbiota

Finegoldia 0.83 0.00 Megamonas 0.33 0.02 Peptostreptococcus 0.00 0.06 Lactobacillus 0.72 0.01 Weissella 0.37 0.01 Parvimonas 0.45 0.01 Parabacteroides 0.84 -0.01 Erysipelotrichaceae Family, cc 115 Genus 0.03 -0.03 Tissierellaceae Family, WAL 1855D Genus 0.68 -0.01 Adlercreutzia 0.43 -0.02 Peptoniphilus 0.81 0.00 Collinsella 0.82 -0.01 Dehalobacterium 0.02 -0.04 Eggerthella 0.23 0.03 Rikenellaceae Undefined Genus 1.00 0.00 Mogibacterium 0.12 -0.02 Odoribacter 0.53 -0.01 Granulicatella 1.00 4.50 x 10-5 Slackia 0.78 -0.01 Campylobacter 0.38 0.02 Lactobacillales Undefined Genus 0.76 -0.01 Erysipelotrichaceae Family, Clostridium Genus 0.62 -0.01 Bulleidia 0.65 -0.01 Anaerotruncus 0.19 -0.03 Porphyromonas 0.10 -0.03 Leuconostoc 0.40 -0.01 Coprobacillus 0.11 -0.03 Acinetobacter 0.61 -0.01 Gemellaceae Undefined Genus 0.07 0.03 TM73 Undefined Genus 0.87 0.00 Oribacterium 0.44 0.02 Allobaculum 0.63 0.01 Christensenella 0.90 0.00 Lactococcus 0.61 -0.01 Desulfovibrio 0.98 0.00 Carnobacteriaceae Undefined Genus 0.34 0.02 Peptococcus 0.86 0.00 Corynebacterium 0.21 0.02 Neisseria 0.01 0.08 Serratia 0.09 0.06 Catenibacterium 0.95 0.00 Anaerostipes 1.00 0.00 Bifidobacteriaceae Undefined Genus 0.72 0.01 Actinomyces 1.00 0.00 Succiniclasticum 0.21 -0.02 Peptococcaceae Undefined Genus 0.63 -0.01 Lachnobacterium 0.66 0.01 Supplementary Table 8. Multivariate correlation between LacMan ratio and Fecal Microbiota

RF32 Undefined Genus 0.72 -0.01 Anaerofustis 0.43 0.01 Varibaculum 0.92 0.00 Rothia 0.28 -0.02 Methanobrevibacter 0.83 0.00 YS2 Undefined Genus 0.85 0.00 Staphylococcus 0.25 0.03 Streptophyta Undefined Genus 0.08 -0.03 S247 Undefined Genus 0.48 0.01 ML615J28 Undefined Genus 0.35 -0.02 Acidaminococcus 0.75 -0.01 Aerococcaceae Undefined Genus 0.92 0.00 Actinobacillus 0.20 0.04 Tissierellaceae Family, Genus ph2 0.47 -0.01 Bilophila 0.83 0.00 Anaerococcus 0.81 0.00 Fusobacterium 0.25 0.03 Pseudobutyrivibrio 0.99 0.00 Pseudoramibacter Eubacterium 0.77 -0.01 Veillonellaceae Undefined Genus 0.22 -0.03 Enterococcus 0.37 0.02 Mobiluncus 0.98 0.00 Victivallaceae Undefined Genus 0.80 0.01 Chryseobacterium 0.71 -0.01 Burkholderiales Undefined Genus 0.71 -0.01 Microvirgula 0.06 0.06 Aggregatibacter 0.75 0.01 Megasphaera 0.06 0.03 Atopobium 0.23 0.02 Flavobacterium 0.51 -0.02 Tissierellaceae Family, Genus 168 0.37 -0.02 Enhydrobacter 0.53 0.02 Scardovia 0.06 0.04 SHA98 Undefined Genus 0.42 -0.01 Actinomycetaceae Undefined Genus 0.48 -0.02 Aeromonadaceae Undefined Genus 0.99 0.00 EtOH8 Undefined Genus 0.75 -0.01

GLS, covariates controlled for, outliers > 6SD excluded Alpha-Diversity Indices P-value Coefficient of correlation Chao1 0.67 -2.05E-05 Simpson 0.67 0.12 Shannon 0.43 -0.011 observed species 0.40 -7.68E-05 PD whole tree 0.13 -0.002

Supplementary Table 8. Multivariate correlation between LacMan ratio and Fecal Microbiota

Dichotomized model (Presence vs. Absence), covariates controlled for Alpha-Diversity Indices P-value Coefficient of correlation Chao1 1.00 0 Simpson 1.00 0 Shannon 1.00 0 observed species 1.00 0 PD whole tree 1.00 0

Generalized least squares model (GLS); phylogenetic diversity whole tree (PD whole tree)

Multivariate correlation between LacMan ratio and fecal microbiota was performed.

Correlation analysis included three taxonomic levels, phylum, family and genus; and

4 measures of alpha-diversity, Chao1 index, Simpson index, Shannon index, observed species and PD whole tree. Analysis was performed treating taxonomic units and alpha-diversity indices as continuous variables (Generalized Least Squares Model) and binary variables (Dichotomized model: Presence vs. Absence). Age, age-squared and gender were included in the all multivariate models with other demographic factors found to significnatly influence the taxonomic unit or index also included. In the multivariate analysis no taxonomic unit or index was significantly corellated with the LacMan ratio.