Supplementary Table 1: List of Modules and Their Associated Kos

Home , Agmatine deiminase

Supplementary Table 1: List of modules and their associated KOs. Modules Description List of KOs K00656/K00132/K04072/K04073/K00001/K00121/K11440/ MF0001 ethanol production (formate pathway) K13953/K13954 MF0002 ethanol production (CO2 pathway) K00001/K00121/K04072/K11440/K13953/K13954 MF0003 acetylglucosamine degradation K00884/K01443/K02564/K02802/K02803/K02804 MF0004 putrescine degradation K00137/K09251/K09471/K09472 acetylneuraminate and acetylmannosamine MF0005 K01639/K00885/K01788 degradation MF0006 urea degradation K14048/K01941/K01457/K01428/K01429/K01430 MF0007 phenylalanine degradation K00832/K00812/K00813/K11358/K00817 tyrosine degradation (hydroxyphenylacetaldehyde MF0008 K00832/K00812/K00813/K11358/K00817/K00055 pathway) MF0009 tryptophan degradation K01667 MF0010 tyrosine degradation (phenol pathway) K01668 MF0011 aspartate degradation (oxaloacetate pathway) K00812/K00813/K11358 MF0012 aspartate degradation (fumarate pathway) K01744 MF0013 glutamate degradation (crotonyl-CoA pathway) K00260/K15371/K00261/K00262/K01615/K01039/K01040 glutamate degradation (4-aminobutanoate MF0014 K01580 pathway) MF0015 glutamate degradation (methylaspartate pathway) K01846/K04835 MF0016 glycine degradation K00281/K00605/K00382/K00282/K00283 MF0017 alanine degradation (racemase pathway) K01775/K00285 MF0018 proline degradation (glutamate pathway) K13821/K00318/K00294 MF0019 proline degradation (aminopentanoate pathway) K01777/K10793/K10794/K10795/K10796 K00826/K00248/K00249/K01692/K01782/K01825/K00020/ MF0020 valine degradation K00382/K11381/K00140/K00822/K07250 MF0021 leucine degradation K00826/K00249/K13766/K01640/K00382/K11381/K01968 K00826/K00248/K00249/K01692/K01782/K01825/K00626/ MF0022 isoleucine degradation K00632/K00382/K11381 MF0023 methionine degradation (cysteine pathway) K00789/K00558/K01251 MF0024 methionine degradation (mercaptan pathway) K01761 MF0025 alanine degradation (glutamate pathway) K00259 MF0026 cysteine biosynthesis/homocysteine degradation K01697/K01758 MF0027 cysteine degradation K01758/K01760 MF0028 serine degradation K01752/K01753 MF0029 threonine degradation (glycine pathway) K00060/K00639/K01620/K00132/K04072/K04073 MF0030 threonine degradation (formate pathway) K01754/K00656 MF0031 asparagine degradation K01424 MF0032 glutamine degradation (ammonia pathway) K01425 MF0033 cysteine degradation (mercaptopyruvate pathway) K00812/K01011/K00813/K11358 MF0034 glutamine degradation (oxoglutarate pathway) K00265/K00266 arginine degradation (agmatine deiminase MF0035 K01583/K01584/K01585/K02626/K10536/K12251 pathway) arginine degradation (ornithine decarboxylase MF0036 K01476/K01581 pathway) arginine degradation (AST/succinyltransferase MF0037 K00673/K01484/K00840/K06447/K05526 pathway) lysine fermentation to acetate and butyrate (3,6- MF0039 K01843/K01844/K00248 diaminohexanoate pathway) MF0040 lysine degradation (cadaverine pathway) K01582 MF0041 histidine degradation K01745/K01712/K01468/K01479/K01458/K00603/K13990 MF0042 4-aminobutyrate degradation K00823/K07250/K00135/K14534 MF0043 arginine degradation (agmatinase pathway) K01583/K01584/K01585/K02626/K01480 MF0044 glycocholate degradation K01442/K00076 MF0045 trehalose degradation K01226/K01194/K05342 MF0046 sucrose degradation K01193/K00847 K01220/K01819/K00917/K08302/K01635/K02786/K02787/ MF0047 lactose and galactose degradation (PTS) K02788 MF0048 lactose degradation K12111/K01190/K12308 MF0049 maltose degradation K00691/K01838 MF0050 melibiose degradation K07406/K07407 MF0051 sucrose degradation (Actinobacteria) K00690/K00847/K01792/K01835 chondroitin sulfate and dermatan sulfate MF0052 K08961 degradation MF0053 allose degradation K00881/K01808 MF0054 arabinose degradation K01804 MF0055 xylose degradation K01805/K00854 MF0056 galactose degradation (Leloir pathway) K01785/K00849/K00965/K01784/K01838 alpha-D-glucose and alpha-D-glucose 1-phosphate MF0057 K00117/K00845/K01053/K01085/K01792/K01835 degradation MF0058 fructose degradation K00882 MF0059 rhamnose degradation K01813/K00848/K01629/K01803 MF0060 ribose degradation K00852 MF0061 mannose degradation K01809 K01176/K07405/K01200/K01208/K00688/K00705/K01187/ MF0062 starch degradation K01178/K01182/K01214 MF0063 fructan degradation K03332 MF0064 pectin degradation K01051/K01184/K01213 pectin degradation - 5-dehydro-4-deoxy-D- MF0065 K01728/K01730/K01815/K00874/K01625 glucuronate degradation MF0066 glycogen metabolism K00975/K00703/K00700/K00688/K01187/K00705 MF0067 PHB production K00023 MF0068 glucarate degradation K01706/K13877/K00042/K01630/K11529 MF0069 galactarate degradation K01708/K13877/K00042/K01630/K11529 MF0070 galactonate degradation K01684/K00883/K01631 MF0071 D-galacturonate degradation K01812/K00041/K01685/K00874 MF0072 ribitol degradation K00875/K01783 MF0073 sorbitol degradation (dehydrogenase) K00008 MF0074 mannitol degradation K00009 sorbitol degradation (phosphotransferase)/sorbose MF0075 K00068 degradation MF0076 arabitol degradation K00854 MF0077 galactitol degradation K00094/K00917/K01635/K08302/K01803 MF0078 xylitol degradation K05351/K00854 MF0079 bifidobacterium shunt K00616/K00615/K01807/K01808/K01783/K01621 K00844/K00845/K01810/K06859/K00850/K01623/K01624/ MF0080 Glycolysis (preparatory phase) K01803 MF0081 Glycolysis (pay-off phase) K00134/K00927/K01834/K01689/K00873 MF0082 pentose phosphate pathway (oxidative branch) K00036/K01057/K07404/K00033 MF0083 pyruvate dehydrogenase complex K00163/K00382/K00627/K00161/K00162 MF0084 pyruvate:ferredoxin oxidoreductase K00169/K00170/K00171/K00172 MF0085 pyruvate:formate lyase K00656 K01647/K01681/K01682/K00031/K00030/K01676/K01679/ K00024/K00116/K00164/K00658/K00382/K01902/K01903/ MF0086 TCA cycle K00239/K00240/K00241/K00242/K00244/K00245/K00246/ K00247/K01677/K01678 K01647/K01681/K01682/K00031/K00030/K01637/K01638/ MF0087 TCA cycle (Mycobacterium pathway) K00024/K00239/K00240/K00241/K00242/K00244/K00245/ K00246/K00247 K01647/K01681/K01682/K00031/K00030/K01676/K01679/ MF0088 TCA cycle (Helicobacter pathway) K00116/K00174/K00175/K00176/K00177/K01028/K01677/ K01678 MF0089 Entner-Doudoroff pathway I K01690/K01625 MF0090 pentose phosphate pathway (non-oxidative branch) K01807/K01808/K01783/K00615/K00616 MF0091 beta-D-glucuronide and D-glucuronate degradation K00040/K00874/K01195/K01686/K01812 K00677/K02535/K02536/K03269/K00748/K00912/K02527/ MF0092 kdo2-lipid A synthesis K02517/K02560 K01938/K01491/K00297/K15023/K05299/K15022/K14138/ MF0093 homoacetogenesis K00196/K00198/K03518/K03519/K03520 MF0094 hydrogen metabolism K00436/K00533/K00534/K06441 MF0095 NADH:ferredoxin oxidoreductase K00529 MF0098 methanogenesis from carbon dioxide K00672/K01499/K00202/K11261/K00441 MF0099 methanol conversion K14080 MF0100 Sulfate reduction (dissimilatory) K00955/K00957/K00956/K00394/K00395/K11180/K11181 MF0101 Sulfate reduction (assimilatory) K00390/K00860/K00955/K00957/K00956/K00380/K00381 K01186/K05970/K01132/K01135/K01137/K01205/K01207/ MF0102 mucin degradation K12373/K01227/K13714/K01206 MF0103 nitrate reduction (assimilatory) K00366/K01915/K00262/K00362 MF0104 nitrate reduction (dissimilatory) K03385 K00368/K00370/K00371/K00374/K00373/K02567/K02568/ MF0105 nitrate reduction (denitrification) K04561 MF0106 anaerobic fatty acid beta-oxidation K06076/K12507/K06445/K00632/K01782 MF0107 glycerol degradation (propanediol pathway) K00086/K06120/K06121 MF0108 glycerol degradation (dihydroxyacetone pathway) K00005/K00863/K01803 MF0109 glycerol degradation (glycerol kinase pathway) K00864/K01126/K00111/K01803/K00112/K00113 MF0110 glyoxylate bypass K01647/K01681/K01682/K01637/K00024/K01596/K01610 MF0111 triacylglycerol degradation K01046 MF0112 acetate to acetyl-CoA K01895 MF0113 acetyl-CoA to acetate K01905/K01067/K00625/K00925 MF0114 acetyl-CoA to crotonyl-CoA K00626/K00023/K01782/K01825/K01715/K01692 MF0115 Crotonyl-coA from succinate K14534/K01902/K01903 MF0116 butyrate production via transferase K00248/K01034/K01035 MF0117 butyrate production via kinase K00248/K00634/K00929 MF0118 formate conversion K05299/K00123/K00124/K00125/K00127/K08348/K08350 MF0119 lactate production K00016/K03777/K03778 MF0120 lactate consumption K00101/K00102 MF0121 propionate production (acrylate pathway) K01026/K00249 MF0122 propionate production (succinate pathway) K01847/K01849/K01848/K05606/K01902/K01903 MF0123 propionate production (propanediol pathway) K00048/K01699/K13919/K13920/K00086/K13922/K13921 MF0124 Fucose degradation K01818/K00879/K01628/K01803 MF0125 propionate production via kinase K13788/K13923/K00932 MF0126 propionate production via transferase K01026 K01596/K01610/K00024/K00116/K01676/K01679/K00873/ MF0127 Succinate production K01958/K01960/K01677/K01678/K00239/K00240/K00241/ K00242/K00244/K00245/K00246/K00247 MF0128 Propionate conversion to succinate K01659/K01720/K01682/K03417 MF0129 catalase K03781/K03782 K00428/K03782/K00432/K00433/K03386/K03564/K11065/ MF0130 peroxidase K07223 MF0131 superoxide dismutase K04564/K04565 MF0132 superoxide reductase K05919 K02523/K00805/K02548/K02551/K08680/K02549/K01911/ MF0133 menaquinone production K01661/K02361/K02552/K11782/K11783/K11784/K11785 M00791 Manganese/zinc transport system K10830/K19971/K19972 M00319 Manganese/zinc/iron transport system K11707/K11708/K11709/K11710 M00241 Vitamin B12 transport system K06073/K06858 M00586 Putative amino-acid transport system K16961/K16962/K16963 M00223 Phosphonate transport system K02041/K02042/K02044 Thiamine biosynthesis, AIR => thiamine- M00127 K00788/K00878/K00941/K00946/K03147/K14153 P/thiamine-2P GABA biosynthesis, eukaryotes, putrescine => M00135 K00128/K00274/K00657 GABA M00300 Putrescine transport system K11073/K11074/K11075/K11076 Lipopolysaccharide biosynthesis, inner core => K02527/K02840/K02841/K02843/K02844/K02847/K02848/ M00080 outer core => O-antigen K02849/K02850/K03278/K03279/K03280 M00027 GABA (gamma-Aminobutyrate) shunt K00135/K00823/K01580/K07250 M00323 Urea transport system K11959/K11960/K11961/K11962/K11963 M00529 Denitrification, nitrate => nitrogen K00368/K00370/K00371/K00374/K02567/K02568/K04561 K00362/K00370/K00371/K00374/K02567/K02568/K03385/ M00530 Dissimilatory nitrate reduction, nitrate => ammonia K15876 M00118 Glutathione biosynthesis, glutamate => glutathione K01919/K01920 M00348 Glutathione transport system K13889/K13890/K13891/K13892 K00194/K00197/K00625/K00925/K01895/K03388/K03389/ M00357 Methanogenesis, acetate => methane K03390/K13788 M00567 Methanogenesis, CO2 => methane K00202/K00672/K01499/K03388/K03389/K03390/K11261 M00191 Thiamine transport system K02062/K02063/K02064 150 functional modules are detailed in the table. 130 modules from GOmixer are coloured in blue while 20 modules from KEGG are coloured in orange.

Supplementary Table 2: Comparison of characteristics before bariatric surgery between obese patients with LSG and LRYGB. LRYGB (89) LSG (108) Total (197) p-value (adjusted) Demographic characteristics 6 (6.7%) - 20 (22.5%) 80 (74.5%) - 18 (16.7%) - 10 86 (43.6%) – 38 <0.001 * Country (France (%) – - 63 (70.8%) (9.3%) (19.3%) - 73 Switzerland (%) – USA(%)) (32.0%) Gender (Female, %) 73 (82%) 75 (69,4%) 148 (75.1%) 0.05 * Age (years) 45 [40-55] 42 [33-53.2] 44 [35-54] 0.07 § 118.1 [107.6-130.8] 120 [106-139.6] 119 [106.4- 0.33 § Weight before surgery (kg) 134.2] BMI before surgery (kg/m2) 42.9 [40.4-46.1] 43.3 [39.7-49.2] 43 [40-48.1] 0.63 § Comorbidities Diabetes prevalence (yes, %) 32 (36.0%) 21 (19.5%) 53 (26.9%) 0.01 * Dyslipidemia (yes, %) 52 (58.4%) 56 (50.9%) 108 (54.8%) 0.39 * Arterial Hypertension (yes, %) 47 (52.8%) 50 (45.5%) 97 (49.2%) 0.40 * Marker Fasting Glycemia 5.3 [4.8-6.3] 5.2 [4.7-6.2] 5.2 [4.7-6.2] 0.471 HbA1c 5.8 [5.5-6.5] 5.7 [5.5-6.2] 5.8 [5.5-6.3] 0.225 Triglycerides 1.5 [1.2-2] 1.4 [1.1-2.1] 1.4 [1.1-2] 0.531 Demographic characteristics and comorbidities of 197 obese patients before bariatric surgery (108 patients with LSG surgery and 89 patients with LRYGB surgery). Data reported in the second and third column are the medians and the interquartile ranges between brackets or percentages between parentheses. Patient’s characteristics were compared between groups using Wilcoxon rank tests § (continuous variable) or Fisher’s exact tests * when appropriate (categorical variables). BMI, Abbreviated Body Mass Index; kg, kilograms.

Supplementary Table 3: Evolution of clinical parameters 6 months after LRYGB LRYGB Baseline 6 Months p-value Weight 118.1 [107.6–130.8] 88.1 [79.6-98.2] <0.001 BMI 42.9 [40.4-46.1] 31.9 [30.5-35.1] <0.001 Diabetes 32 (36%) 13 (14.6%) - (prevalence) HbA1c 5.85 [5.5-6.45] 5.5 [5.3-6.35] 0.079 Fasting_glycemia 5.3 [4.8-6.3] 5 [4.5-5.5] 0.042 Triglycerides 1.48 [1.19-2.00] 1.09 [0.92-1.27] <0.001 Evolution of weight, BMI and other clinical parameters of 89 patients with LRYGB surgery. Data reported are the medians and the interquartile ranges between brackets for the weight and BMI at baseline and 6-month post-surgery. Pre and post-operative clinical parameters were compared using Wilcoxon signed-rank test.

Supplementary Table 4: Evolution of clinical parameters 6 months after LSG LSG Baseline 6 Months p-value Weight 119.9 [106-139.1] 95 [80-106.5] <0.001 BMI 43.3 [39.7-49.2] 33.4 [29.29-38-74] <0.001 Diabetes 21 (19.4%) 13 (12%) - (prevalence) HbA1c 5.7 [5.5-6.25] 5.5 [5-5.85] 0.003 Fasting_glycemia 5.2 [4.7-6.2] 4.71 [4.4-5.2] <0.001 Triglycerides 1.38 [1.08-2.07] 1.21 [0.89-1.57] 0.030 Evolution of weight, BMI and other clinical parameters of 108 patients with LSG surgery. Data reported are the medians and the interquartile ranges between brackets for the weight and BMI at baseline and 6-month post-surgery. Pre and post-operative clinical parameters were compared using Wilcoxon signed-rank test.

Supplementary Table 5: MSP significantly modulated by LRYGB Species FDR MSP Phylum Annotation Increased in FC (log2) Annotation adj p-value msp_0873 Firmicutes Veillonella atypica 6 Months 3.35 <0.001 msp_1070 Firmicutes Streptococcus parasanguinis 6 Months 3.18 <0.001 msp_1507 Firmicutes Streptococcus oralis 6 Months 1.34 <0.001 msp_0417 Proteobacteria Klebsiella pneumoniae 6 Months 4.03 <0.001 msp_1219 Firmicutes Veillonella parvula 6 Months 2.65 <0.001 msp_1296 Firmicutes Streptococcus salivarius 6 Months 4.07 <0.001 msp_1714 Firmicutes Streptococcus gordonii 6 Months 1.53 <0.001 msp_1390 Firmicutes Streptococcus oralis 6 Months 1.33 <0.001 msp_0027 Firmicutes Clostridium symbiosum 6 Months 2.24 <0.001 msp_0114 Firmicutes Enterococcus faecalis 6 Months 2.84 <0.001 msp_0868 NA NA 6 Months 3.75 <0.001 msp_0646 Fusobacteria Fusobacterium nucleatum 6 Months 2.12 <0.001 msp_1625 Firmicutes Streptococcus vestibularis 6 Months 1.35 <0.001 msp_1034 Firmicutes Streptococcus anginosus 6 Months 1.37 <0.001 msp_0035 Proteobacteria Escherichia coli 6 Months 5.22 <0.001 msp_1251 Firmicutes Streptococcus mutans 6 Months 1.26 <0.001 msp_1288 Verrucomicrobia Akkermansia muciniphila 6 Months 1.61 <0.001 msp_0566 Firmicutes Roseburia hominis 6 Months 2.72 <0.001 msp_1508 Firmicutes Veillonella sp. oral 6 Months 1.1 <0.001 msp_1026 Firmicutes Eubacterium rectale Baseline -2.8 <0.001 msp_1351 Proteobacteria Haemophilus parainfluenzae 6 Months 1.61 <0.001 msp_0011 Firmicutes Hungatella hathewayi 6 Months 1.15 <0.001 msp_0513 Firmicutes Oscillibacter sp. KLE Baseline -1.48 <0.001 msp_0103 Firmicutes Clostridium sp. AT5 Baseline -1.54 <0.001 msp_0560 Firmicutes Flavonifractor plautii Baseline -1.25 <0.001 msp_0344 NA NA 6 Months 5.76 <0.001 msp_1045 NA NA Baseline -1.98 <0.001 msp_1271 Firmicutes Faecalibacterium cf. prausnitzii Baseline -1.43 <0.001 msp_1046 Bacteroidetes Alistipes finegoldii 6 Months 1.39 <0.001 msp_0284 Firmicutes Ruminococcus gnavus Baseline -1.74 <0.001 msp_1512 Firmicutes NA Baseline -5.97 <0.001 msp_1376 Bacteroidetes Alistipes shahii 6 Months 1.31 <0.001 msp_0711 Firmicutes Blautia obeum 6 Months 1.47 0.001 msp_0565 NA NA Baseline -1.06 0.001 msp_0582 Firmicutes NA 6 Months 1.19 0.001 msp_1334 Euryarchaeota Methanobrevibacter smithii 6 Months 2.11 0.001 msp_0022 Firmicutes NA 6 Months 1.22 0.001 msp_0834 Bacteroidetes Alistipes finegoldii 6 Months 1.92 0.001 msp_0652 Actinobacteria Bifidobacterium bifidum Baseline -2.23 0.002 msp_1118 Bacteroidetes Bacteroides cellulosilyticus 6 Months 1.61 0.002 msp_0078 Firmicutes Clostridium saudii Baseline -1.18 0.005 msp_0240 Firmicutes NA Baseline -2.31 0.005 msp_0745 NA NA Baseline -1.01 0.016 msp_1441 Firmicutes Eubacterium eligens 6 Months 3.39 0.016 msp_0345 NA NA Baseline -1.88 0.017 msp_0803 Firmicutes Anaerostipes hadrus Baseline -1.03 0.017 msp_0682 NA NA 6 Months 1.12 0.017 msp_0355 NA NA 6 Months 1.28 0.02 msp_0487 NA NA Baseline -1.03 0.027 msp_0554 Firmicutes Ruminococcus torques Baseline -1.91 0.027 msp_1329 NA NA Baseline -1.37 0.039

Supplementary Table 6: MSP significantly modulated by LSG Species FDR MSP Phylum Annotation Increased in FC (log2) Annotation adj p-value msp_0492 Actinobacteria Bifidobacterium dentium 6 Months 1.01 <0.001 msp_0868 NA NA 6 Months 2.12 <0.001 msp_1714 Firmicutes Streptococcus gordonii 6 Months 1.04 <0.001 msp_1219 Firmicutes Veillonella parvula 6 Months 1.92 <0.001 msp_1251 Firmicutes Streptococcus mutans 6 Months 1.1 <0.001 msp_1070 Firmicutes Streptococcus parasanguinis 6 Months 2.32 <0.001 msp_0027 Firmicutes Clostridium symbiosum 6 Months 1.12 <0.001 msp_0486 NA NA 6 Months 1.25 <0.001 msp_1288 Verrucomicrobia Akkermansia muciniphila 6 Months 1.82 <0.001 msp_1296 Firmicutes Streptococcus salivarius 6 Months 1.98 <0.001 msp_0344 NA NA 6 Months 1.02 <0.001 msp_0834 Bacteroidetes Alistipes finegoldii 6 Months 1.9 <0.001 msp_1026 Firmicutes Eubacterium rectale Baseline -2.02 <0.001 msp_0417 Proteobacteria Klebsiella pneumoniae 6 Months 2.09 <0.001 msp_1351 Proteobacteria Haemophilus parainfluenzae 6 Months 1.4 <0.001 msp_0007 Firmicutes Clostridium sp. KLE 6 Months 1.65 <0.001 msp_0321 Bacteroidetes Alistipes indistinctus 6 Months 1.04 <0.001 msp_0363 Bacteroidetes Barnesiella intestinihominis 6 Months 1.34 <0.001 msp_1537 Bacteroidetes NA 6 Months 1.91 <0.001 msp_1207 NA NA 6 Months 1.75 <0.001 msp_0665 Firmicutes Clostridium scindens 6 Months 1.02 <0.001 msp_1706 Firmicutes NA 6 Months 1.05 <0.001 msp_0135 Bacteroidetes Bacteroides caccae 6 Months 1.27 <0.001 msp_0530 Firmicutes NA 6 Months 1.08 <0.001 msp_0691 NA NA 6 Months 1.32 <0.001 msp_0422 Verrucomicrobia NA 6 Months 1.42 <0.001 msp_0769 NA NA 6 Months 2.18 <0.001 msp_1046 Bacteroidetes Alistipes finegoldii 6 Months 1.11 <0.001 msp_0035 Proteobacteria Escherichia coli 6 Months 1.04 <0.001 msp_1094 NA NA 6 Months 1.17 0.001 msp_1079 NA NA 6 Months 1.14 0.001 msp_0598 Firmicutes Roseburia faecis Baseline -1.44 0.001 msp_1159 Firmicutes Lachnoclostridium sp. YL32 6 Months 1.02 0.002 msp_0015 Firmicutes Clostridium bolteae 6 Months 1.11 0.002 msp_0103 Firmicutes Clostridium sp. AT5 Baseline -1.03 0.002 msp_0582 Firmicutes NA 6 Months 1.27 0.005 msp_0118 Bacteroidetes Bacteroides fragilis 6 Months 1.37 0.006 msp_1326 Firmicutes Roseburia intestinalis Baseline -2.53 0.006 msp_0654 Firmicutes Ruminococcus lactaris 6 Months 2.23 0.009 msp_1553 Bacteroidetes Bacteroides dorei 6 Months 1.37 0.011 msp_1441 Firmicutes Eubacterium eligens 6 Months 1.83 0.012 msp_0711 Firmicutes Blautia obeum 6 Months 1.07 0.013 msp_0572 Firmicutes Lachnospira pectinoschiza Baseline -3.18 0.018 msp_0355 NA NA 6 Months 1.25 0.026 msp_0746 NA NA 6 Months 1.13 0.045 msp_0752 Firmicutes Eubacterium ramulus Baseline -1.38 0.047 msp_1279 Firmicutes Ruminococcus bromii Baseline -2.18 0.048

Supplementary Table 7: Comparison in modulation between LRYGB and LSG Median of Median of Species FDR MSP Phylum Annotation ratios ratios Annotation adj p-value for LRYGB for LSG msp_0873 Firmicutes Veillonella atypica 3.341 0.714 <0.001 msp_1296 Firmicutes Streptococcus salivarius 3.711 1.611 <0.001 msp_0513 Firmicutes Oscillibacter sp. KLE -1.358 0.13 <0.001 msp_0560 Firmicutes Flavonifractor plautii -1.077 0.236 <0.001 msp_1070 Firmicutes Streptococcus parasanguinis 3.351 1.674 <0.001 msp_0035 Proteobacteria Escherichia coli 3.205 0.858 <0.001 msp_0565 NA NA -0.971 0.521 <0.001 msp_0566 Firmicutes Roseburia hominis 2.447 0.368 <0.001 msp_0114 Firmicutes Enterococcus faecalis 3.948 0.849 <0.001 msp_1045 NA NA -1.868 0.184 <0.001 msp_0652 Actinobacteria Bifidobacterium bifidum -0.692 0.244 0.001 msp_0803 Firmicutes Anaerostipes hadrus -0.602 0.405 0.001 msp_0284 Firmicutes Ruminococcus gnavus -1.486 -0.062 0.001 msp_1390 Firmicutes Streptococcus oralis 1.479 0.513 0.001 msp_1507 Firmicutes Streptococcus oralis 1.39 0.687 0.001 msp_0598 Firmicutes Roseburia faecis 0.891 -1.181 0.002 msp_0417 Proteobacteria Klebsiella pneumoniae 4.741 2.226 0.002 msp_0007 Firmicutes Clostridium sp. KLE 0 1.061 0.003 msp_0345 NA NA -0.456 0.302 0.007 msp_1219 Firmicutes Veillonella parvula 2.634 1.681 0.011 msp_1508 Firmicutes Veillonella sp. oral 1.228 0.21 0.011 msp_0486 NA NA 0.64 1.465 0.033 msp_0487 NA NA -0.669 0.019 0.049 msp_0691 NA NA 0 0.963 0.049

Supplementary Table 8: Functional modules significantly impacted by LRYGB FDR Modules Description Modules Increased in FC log2 adj p-value M00225 Lysine/arginine/ornithine transport system 6 Months 5.16 <0.001 M00226 Histidine transport system 6 Months 5.51 <0.001 M00791 Manganese/zinc transport system 6 Months 3.3 <0.001 M00241 Vitamin B12 transport system 6 Months 5.23 <0.001 MF0105 nitrate reduction (denitrification) 6 Months 1 <0.001 M00191 Thiamine transport system 6 Months 2.19 <0.001 M00300 Putrescine transport system 6 Months 4.95 <0.001 MF0128 Propionate conversion to succinate 6 Months 1.07 <0.001 sorbitol degradation MF0075 6 Months 1.39 <0.001 (phosphotransferase)/sorbose degradation MF0125 propionate production via kinase 6 Months 2.53 <0.001 M00323 Urea transport system 6 Months 2.01 <0.001 MF0095 NADH:ferredoxin oxidoreductase 6 Months 1.65 <0.001 M00319 Manganese/zinc/iron transport system 6 Months 3.39 <0.001

Supplementary Table 9: Functional modules significantly impacted by LSG FDR Modules Description Modules Increased in FC log2 adj p-value glutamate degradation MF0015 6 Months 1.39 <0.001 (methylaspartate pathway) M00791 Manganese/zinc transport system 6 Months 2.04 <0.001 M00241 Vitamin B12 transport system 6 Months 1.49 <0.001 M00226 Histidine transport system 6 Months 1.18 0.001 M00225 Lysine/arginine/ornithine transport system 6 Months 1.16 0.001 M00300 Putrescine transport system 6 Months 1.6 0.007

Supplementary Table 10: Comparison of functional modules between LRYGB and LSG Median of ratios Median of ratios FDR Modules Description Modules for LRYGB for LSG adj p-value M00225 Lysine/arginine/ornithine transport system 36.516 2.393 <0.001 M00226 Histidine transport system 54.377 2.555 <0.001 M00241 Vitamin B12 transport system 21.396 2.821 <0.001 MF0105 nitrate reduction (denitrification) 1.949 1.123 <0.001 M00300 Putrescine transport system 22.711 2.39 <0.001 MF0125 propionate production via kinase 5.69 1.458 <0.001 M00191 Thiamine transport system 3.805 1.566 <0.001 MF0128 Propionate conversion to succinate 1.986 1.247 <0.001 M00791 Manganese/zinc transport system 8.638 3.208 <0.001 M00323 Urea transport system 3.614 1.369 0.001 sorbitol degradation MF0075 2.6 1.463 0.001 (phosphotransferase)/sorbose degradation MF0095 NADH:ferredoxin oxidoreductase 4.382 1.691 0.008 M00319 Manganese/zinc/iron transport system 5.869 1.958 0.047

Supplementary Table 11: Correlation between functional modules and MSP Surgery Cor. Factor MSP Modules pvalue Type (spearman) LSG msp_1070 M00791 0.90 >10-5 Streptococcus parasanguinis Manganese/zinc transport system msp_1296 M00791 0.88 >10-5 Streptococcus salivarius Manganese/zinc transport system

M00225 0.77 >10-5 msp_0035 Lysine/arginine/ornithine transport system Escherichia coli M00226 0.77 >10-5 Histidine transport system LRYGB MF0125 0.76 >10-5 Propionate production via kinase MF0128 0.70 >10-5 Propionate conversion to succinate M00241 0.84 >10-5 msp_0035 Vit. B12 transport system Escherichia coli M00300 0.85 >10-5 Putrescin transport system M00225 0.85 >10-5 Lysine/arginine/ornithine transport system

M00226 0.86 >10-5 Histidine transport system msp_1070 M00791 0.91 >10-5 Streptococcus parasanguinis Manganese/zinc transport system msp_1219 M00319 0.71 >10-5 Veillonella parvula Manganese/zinc/iron transport system msp_1296 M00791 0.91 >10-5 Streptococcus salivarius Manganese/zinc transport system msp_1625 M00791 0.70 >10-5 Streptococcus vestibularis Manganese/zinc transport system

Supplementary Table 12: KOs related to TMAO respiration LRYGB LSG KO Protein name Description p.value p.value trimethylamine-N-oxide reductase K07821 2.34*10-10 6.19*10-5 torY (cytochrome c), cytochrome c-type subunit TorY trimethylamine-N-oxide reductase K03532 2.10*10-6 9.77*10-1 torC (cytochrome c), cytochrome c-type subunit TorC trimethylamine-N-oxide reductase (cytochrome c) K07812 2.34*10-6 4.97*10-1 torZ [EC:1.7.2.3]

Supplementary Figure 1

PCA based on log transformed MSPs abundances. Separation between patients from USA and Europe before surgery (A). Separation of patients who underwent LRYGB and LSG before surgery (B). No separation for Swiss patients before surgery (C). Supplementary Figure 2

Shannon microbial diversity and gene richness. Compared to baseline, the Shannon index (left side) was significantly increased by surgery after 6 months (Wilcoxon signed-rank test, LRYGB: p=7.5*10-6 and LSG: p=7.3*10-11). Gene richness (right side) was also significantly higher 6 months after LRYGB (Wilcoxon signed-rank test, LRYGB: p=3.8*10-5 and after LSG:p=5.9*10-10). Supplementary Figure 3

Phylum-level composition of patients (median of relative abundance) before surgery and after LRYGB and LSG. The phyla with abundances superior to 0.1% were represented.

Supplementary Figure 4

Relative abundances of 51 MSPs that were significantly impacted by LRYGB. MSPs were grouped by phylum and ordered according their fold change within the phylum.

Supplementary Figure 5

Relative abundances of 49 MSPs that were significantly impacted by LSG. MSPs were grouped by phylum and ordered according their fold change within the phylum.

Supplementary Figure 6

Relative abundances of 13 modules that were significantly impacted by LRYGB. Modules were grouped by functional category and ordered according their fold change values.

Supplementary Figure 7

Relative abundances of 6 modules that were significantly impacted by LSG. Modules were grouped by functional category and ordered according their fold change values.