SUPPLEMENTARY DATA

Supplementary Table 1. Bacterial differences between chow and HF‐feeding

High-Fat Diet Chow Diet P-values High-Fat Diet Chow Diet P-values Phylum Genus Mean SD FQ (%) Mean SD FQ (%) HF vs Chow Phylum Genus Mean SD FQ (%) Mean SD FQ (%) HF vs Chow Actinobacteria Bifidobacterium 0.00 0.00 0.00 0.00 0.01 11.11 0.3428 Marvinbryanti a 0.00 0.01 10.00 0.06 0.05 77.78 0.0031 Actinobacteria Adlercreutzia 0.04 0.04 50.00 0.01 0.02 11.11 0.0671 Firmicutes Moryella 0.00 0.00 0.00 0.10 0.08 88.89 0.0003 Actinobacteria Asaccharobacter 0.01 0.01 20.00 0.00 0.00 0.00 0.1930 Firmicutes Oribacterium 0.00 0.01 10.00 0.02 0.01 66.67 0.0083 Actinobacteria Coriobacterium 0.00 0.00 0.00 0.00 0.00 0.00 NA Firmicutes Parasporobacteriu m 0.00 0.00 0.00 0.05 0.06 55.56 0.0099 Actinobacteria Cryptobacterium 0.00 0.00 0.00 0.00 0.01 11.11 0.3428 Firmicutes Pseudobutyrivibrio 0.00 0.00 0.00 0.01 0.01 22.22 0.1457 Actinobacteria Enterorhabdus 0.01 0.02 20.00 0.00 0.00 0.00 0.1930 Firmicutes Robinsoniella 0.02 0.05 10.00 0.24 0.15 88.89 0.0008 Actinobacteria Olsenella 0.00 0.00 0.00 0.01 0.01 22.22 0.1457 Firmicutes Roseburi a 0.77 0.53 100.00 0.64 0.57 100.00 0.4470 Actinobacteria Paraeggerthella 0.00 0.00 0.00 0.01 0.01 22.22 0.1457 Firmicutes Syntrophococcus 0.00 0.00 0.00 0.01 0.03 33.33 0.0624 Actinobacteria Corynebacterium 0.01 0.03 20.00 0.00 0.00 0.00 0.1930 Firmicutes unclassified_Lachnospiraceae 9.81 4.46 100.00 39.77 4.00 100.00 0.0000 Actinobacteria Rothia 0.03 0.07 30.00 0.00 0.01 11.11 0.3306 Firmicutes Desulfonispora 0.03 0.02 70.00 0.01 0.02 22.22 0.0774 Ascomycota Saccharomyces 0.00 0.00 0.00 0.01 0.01 22.22 0.1457 Firmicutes Peptococcus 2.84 0.79 100.00 0.17 0.12 88.89 0.0000 Bacteroidetes Bacteroides 24.74 10.69 100.00 1.25 0.48 100.00 0.0000 Firmicutes Clostridium_XI 1.33 0.39 100.00 0.14 0.14 77.78 0.0003 Bacteroidetes Barnesiella 2.21 1.70 100.00 6.23 3.31 100.00 0.0021 Firmicutes Acetanaerobacteriu m 0.00 0.00 0.00 0.06 0.07 66.67 0.0035 Bacteroidetes Dysgonomonas 0.00 0.00 0.00 0.00 0.01 11.11 0.3428 Firmicutes 0.39 0.49 80.00 0.21 0.17 100.00 1.0000 Bacteroidetes Parabacteroides 0.82 0.26 100.00 0.10 0.07 100.00 0.0000 Firmicutes 0.08 0.05 90.00 0.67 0.64 100.00 0.0000 Bacteroidetes Porphyromonas 0.04 0.07 40.00 0.11 0.07 100.00 0.0181 Firmicutes 0.13 0.14 90.00 0.44 0.26 100.00 0.0030 Bacteroidetes Tannerella 0.00 0.00 0.00 0.01 0.02 33.33 0.0624 Firmicutes Clostridium_III 0.08 0.09 60.00 0.09 0.04 100.00 0.6519 Bacteroidetes unclassified_Porphyromonadaceae 0.98 0.92 90.00 5.95 2.11 100.00 0.0000 Firmicutes Clostridium_IV 3.59 1.99 100.00 4.27 1.42 100.00 0.6038 Bacteroidetes Hallella 0.00 0.00 0.00 0.01 0.03 22.22 0.1457 Firmicutes Ethanoligenens 0.03 0.10 20.00 0.04 0.06 55.56 0.2028 Bacteroidetes Prevotella 0.04 0.08 40.00 1.06 0.39 100.00 0.0002 Firmicutes Faecalibacteriu m 0.02 0.04 20.00 0.00 0.00 0.00 0.1930 Bacteroidetes unclassified_Prevotellaceae 0.00 0.00 0.00 0.04 0.05 55.56 0.0099 Firmicutes Flavonifractor 1.42 0.92 100.00 0.16 0.09 100.00 0.0021 Bacteroidetes Alistipes 9.47 5.04 100.00 0.98 0.65 100.00 0.0030 Firmicutes Hydrogenoanaerobacterium 0.07 0.08 70.00 0.14 0.12 100.00 0.0546 Bacteroidetes Sphingobacterium 0.00 0.00 0.00 0.00 0.01 11.11 0.3428 Firmicutes Oscillibacte r 1.38 0.91 90.00 6.80 2.23 100.00 0.0000 Deferribacteres M ucispirillum 0.11 0.32 20.00 0.07 0.05 77.78 0.0470 Firmicutes Pseudoflavonifractor 0.37 0.26 90.00 2.05 1.08 100.00 0.0000 Euryarchaeota Pyrococcus 0.00 0.00 0.00 0.00 0.01 11.11 0.3428 Firmicutes Ruminococcus 5.68 4.35 80.00 1.44 0.93 100.00 0.0940 Firmicutes Globicatella 0.00 0.01 10.00 0.00 0.00 0.00 0.3991 Firmicutes Sporobacter 0.02 0.04 20.00 0.05 0.05 77.78 0.0703 Firmicutes Sediminibacillus 0.00 0.00 0.00 0.01 0.02 11.11 0.3428 Firmicutes unclassified_Ruminococcaceae 3.32 1.90 100.00 7.25 2.58 100.00 0.0003 Firmicutes Enterococcus 0.01 0.02 30.00 0.00 0.00 0.00 0.0947 Firmicutes unclassified_Clostridiales 1.76 1.37 100.00 2.43 0.95 100.00 0.4470 Firmicutes Lactobacillus 0.25 0.25 90.00 0.30 0.14 100.00 0.2110 Firmicutes Clostridium_XVIII 0.01 0.02 30.00 0.00 0.00 0.00 0.0947 Firmicutes Staphylococcus 0.01 0.02 10.00 0.01 0.02 11.11 0.9390 Firmicutes 0.02 0.03 40.00 0.00 0.00 0.00 0.0452 Firmicutes Lactococcus 0.06 0.06 60.00 0.00 0.00 0.00 0.0087 Firmicutes Erysipelotrichaceae_incertae_sedis 0.07 0.08 60.00 0.00 0.00 0.00 0.0087 Firmicutes Streptococcus 0.03 0.04 50.00 0.00 0.00 0.00 0.0205 Firmicutes Holdemania 0.01 0.02 20.00 0.00 0.00 0.00 0.1930 Firmicutes Anaerosporobacter 0.02 0.03 30.00 0.17 0.14 88.89 0.0051 Firmicutes Turicibacter 0.43 0.35 80.00 0.04 0.07 55.56 0.0181 Firmicutes 0.00 0.00 0.00 0.00 0.01 11.11 0.3428 Firmicutes Dialister 0.01 0.04 10.00 0.00 0.00 0.00 0.3991 Firmicutes Clostridium_sensu_stricto 5.30 2.45 100.00 0.12 0.16 55.56 0.0003 Firmicutes Mitsuokella 0.01 0.05 10.00 0.00 0.00 0.00 0.3991 Firmicutes Fervidicella 0.00 0.00 0.00 0.01 0.02 11.11 0.3428 Firmicutes Selenomonas 0.00 0.00 0.00 0.05 0.02 100.00 0.0001 Firmicutes 0.00 0.00 0.00 0.00 0.01 11.11 0.3428 Firmicutes unclassified_Firmicutes 0.00 0.01 10.00 0.04 0.05 55.56 0.0334 Firmicutes unclassified_Clostridiaceae_1 0.04 0.14 10.00 0.00 0.00 0.00 0.3991 Proteobacteri a Gemmiger 0.01 0.04 10.00 0.00 0.00 0.00 0.3991 Firmicutes 0.00 0.00 0.00 0.00 0.01 11.11 0.3428 Proteobacteria Kiloniella 0.18 0.37 40.00 0.07 0.09 55.56 0.7573 Firmicutes 0.00 0.00 0.00 0.00 0.01 11.11 0.3428 Proteobacteria Fodinicurvata 0.00 0.00 0.00 0.00 0.01 11.11 0.3428 Firmicutes Sporosalibacterium 0.00 0.00 0.00 0.00 0.01 11.11 0.3428 Proteobacteri a Insolitispirillum 0.17 0.26 50.00 0.02 0.02 55.56 0.4122 Firmicutes Sporanaerobacter 0.00 0.00 0.00 0.00 0.01 11.11 0.3428 Proteobacteri a Rhodospirillum 0.00 0.01 10.00 0.01 0.02 11.11 0.9390 Firmicutes Anaerovorax 0.01 0.03 10.00 0.10 0.06 100.00 0.0007 Proteobacteria Janthinobacterium 0.01 0.02 10.00 0.00 0.00 0.00 0.3991 Firmicutes Eubacterium 0.20 0.28 50.00 0.10 0.07 88.89 1.0000 Proteobacteri a Parasutterella 2.22 1.20 100.00 0.33 0.27 100.00 0.0003 Firmicutes Gracilibacter 0.00 0.00 0.00 0.01 0.03 22.22 0.1457 Proteobacteri a Vampirovibrio 0.00 0.00 0.00 0.01 0.02 11.11 0.3428 Firmicutes Clostridium_XII 0.00 0.00 0.00 0.00 0.01 11.11 0.3428 Proteobacteria Helicobacter 0.01 0.02 10.00 0.00 0.00 0.00 0.3991 Firmicutes Anaerostipes 0.18 0.30 30.00 0.17 0.08 100.00 0.1428 Proteobacteria Aeromonas 0.00 0.00 0.00 0.01 0.01 22.22 0.1457 Firmicutes Blautia 7.95 3.81 100.00 0.23 0.18 100.00 0.0000 Proteobacteria Enterobacter 0.01 0.01 20.00 0.00 0.00 0.00 0.1930 Firmicutes 0.00 0.00 0.00 0.00 0.01 11.11 0.3428 Proteobacteria Escherichia/Shigella 1.00 1.39 80.00 0.18 0.16 88.89 0.3066 Firmicutes Clostridium_XlVa 3.73 1.76 100.00 13.14 5.00 100.00 0.0001 Proteobacteria Proteus 0.05 0.06 60.00 0.00 0.01 11.11 0.0208 Firmicutes Clostridium_XlVb 3.39 1.05 100.00 0.10 0.10 77.78 0.0003 Proteobacteria unclassified_Enterobacteriaceae 0.00 0.01 10.00 0.00 0.01 11.11 0.9390 Firmicutes Coprococcus 0.70 0.83 90.00 0.04 0.03 55.56 0.0074 Proteobacteria Acinetobacter 0.03 0.09 10.00 0.00 0.00 0.00 0.3991 Firmicutes 0.01 0.02 10.00 0.04 0.07 33.33 0.2294 Proteobacteri a Pasteurella 0.06 0.12 40.00 0.02 0.03 44.44 0.8203 Firmicutes Hespellia 0.00 0.00 0.00 0.01 0.02 11.11 0.3428 Proteobacteri a unclassified_Pasteurellaceae 0.00 0.00 0.00 0.00 0.01 11.11 0.3428 Firmicutes Johnsonella 0.00 0.00 0.00 0.04 0.08 44.44 0.0256 Tenericutes Anaeroplasm a 0.05 0.10 20.00 0.01 0.03 11.11 0.5630 Firmicutes Lachnospiracea_incertae_sedis 1.96 1.41 100.00 0.97 0.51 100.00 0.0535 unclassified_Bacteria unclassified_Bacteria 0.11 0.15 70.00 0.33 0.37 100.00 0.0787 Firmicutes Lactonifactor 0.00 0.00 0.00 0.00 0.01 11.11 0.3428 Verrucomicrobia Akkermansia 0.03 0.05 40.00 0.00 0.00 0.00 0.0452

©2014 American Diabetes Association. Published online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db13-1526/-/DC1 SUPPLEMENTARY DATA

Supplementary Table 2. Bacterial differences between OP and OR and CVOP and CVOR animals during high‐fat feeding

OP OR CVOP CVOR p-value 1st HIT AN E- S_ab FQ FQ FQ FQ p-value OP CVOP vs Phylum Genus GenBank score Seqmatch 1st isolate score Mean SD (%) Mean SD (%) Mean SD (%) Mean SD (%) vs OR CVOR Adlercreutzia equolifaciens; FJC-M48; Actinobacteria Uncl. Coriobacterineae gb|GU241872.1| 0.0 AB434709 0.980 0.03 0.05 29 0.03 0.05 50 0.06 0.08 60 0.01 0.02 25 0.743 0.227 Actinobacteria Uncl. Coriobacterineae gb|GQ300123.1| 0.0 Enterorhabdus caecimuris (T); B7; DQ789120 0.885 0.00 0.01 14 0.02 0.03 25 0.03 0.02 80 0.06 0.12 25 0.674 0.443 Enterorhabdus mucosicola (T); type strain: Actinobacteria Uncl. Coriobacterineae gb|JF254730.1| 0.0 Mt1B8; AM747811 1.000 0.00 0.00 0 0.00 0.00 0 0.01 0.02 40 0.04 0.03 75 NA 0.201 Bacteroidetes Alistipes gb|JF246324.1| 0.0 Alistipes finegoldii; ANH 2437; AJ518874 0.802 3.87 0.54 100 2.26 2.09 100 4.19 2.46 100 6.37 2.60 100 0.230 0.191 Bacteroidetes Alistipes gb|HQ789275.1| 0.0 Alistipes finegoldii; CIP 107999; AY643084 0.993 0.93 0.56 100 0.08 0.05 100 1.69 1.16 100 0.56 0.18 100 0.006 0.063 Bacteroidetes Alistipes gb|FJ838147.1| 0.0 Bacteroides sp. Smarlab 3302398; AY538696 0.849 0.02 0.06 14 0.00 0.00 0 0.00 0.00 0 0.00 0.00 0 0.571 NA Bacteroidetes Bacteroides gb|JQ894003.1| 0.0 Bacteroides acidifaciens; A29; AB021160 0.976 2.03 1.40 100 5.42 3.88 100 2.80 1.52 100 3.54 1.23 100 0.042 0.556 Bacteroidetes Bacteroides gb|JQ084931.1| 0.0 Bacteroides acidifaciens; A43; AB021165 0.993 0.12 0.10 100 0.44 0.43 100 0.28 0.17 100 0.35 0.26 100 0.164 1.000 Bacteroidetes Bacteroides gb|JQ084931.1| 0.0 Bacteroides acidifaciens; A43; AB021165 1.000 0.04 0.03 86 0.19 0.16 75 0.06 0.07 80 0.07 0.08 100 0.185 0.730 Bacteroidetes Bacteroides gb|JQ891250.1| 0.0 Bacteroides acidifaciens; SLC1-3; AB599942 0.992 4.19 1.95 100 2.21 0.60 100 4.11 3.67 100 1.83 0.89 100 0.006 0.413 Bacteroidetes Bacteroides gb|HQ789470.1| 0.0 Bacteroides caccae; JCM9498; EU136686 0.970 0.36 0.75 57 3.98 2.44 100 0.97 1.27 80 0.71 0.50 100 0.010 0.905 Bacteroidetes Bacteroides gb|JQ317269.1| 3E-149 Bacteroides vulgatus ATCC 8482; CP000139 1.000 2.90 1.01 100 5.04 0.70 100 1.90 0.61 100 1.01 0.51 100 0.012 0.111 Bacteroidetes Bacteroides gb|JQ607721.1| 0.0 Bacteroides vulgatus; BCRC12903; EU136687 0.995 10.59 4.26 100 16.95 1.96 100 6.28 1.33 100 3.54 1.67 100 0.042 0.032 Bacteroidetes Bacteroides gb|HQ792859.1| 0.0 Bacteroides vulgatus; DJF_B081; EU728705 0.984 0.10 0.07 86 0.08 0.05 100 0.07 0.05 100 0.00 0.00 0 0.927 0.015 Barnesiella intestinihominis (T); YIT 11860; Bacteroidetes Barnesiella gb|FJ835261.1| 0.0 AB370251 0.667 0.72 0.35 100 0.21 0.28 75 3.09 2.12 100 3.98 1.96 100 0.073 0.730

Bacteroidetes Barnesiella gb|JQ893854.1| 0.0 Gram-negative bacterium cL10-2b-4; AY239469 0.745 1.30 0.42 100 0.52 0.53 100 2.51 1.25 100 1.68 0.53 100 0.073 0.286 Bacteroidetes Parabacteroides dbj|AB702762.1| 0.0 Bacteroides sp. ASF519; ASF 519; AF157056 1.000 0.02 0.04 29 0.04 0.06 50 0.58 0.98 100 1.83 0.51 100 0.584 0.111 Parabacteroides distasonis; JCM5825; Bacteroidetes Parabacteroides gb|EU457296.1| 3E-171 EU136681 0.637 0.49 0.47 86 0.03 0.04 50 0.00 0.00 0 0.00 0.00 0 0.070 NA Parabacteroides goldsteinii; JCM13446; 14; Bacteroidetes Parabacteroides dbj|AB702762.1| 0.0 EU136697 0.995 0.72 0.27 100 0.76 0.24 100 10.73 3.40 100 8.80 2.39 100 0.927 0.556 Bacteroidetes Porphyromonas gb|JF259494.1| 0.0 Porphyromonas sp. MI10-1288x; HM583587 0.671 0.02 0.03 29 0.00 0.00 0 0.17 0.10 100 0.22 0.06 100 0.327 0.413 Bacteroidetes Prevotella gb|JQ892741.1| 0.0 Prevotella sp. DJF_B116; EU728713 0.708 0.01 0.03 29 0.00 0.00 0 0.00 0.00 0 0.02 0.02 50 0.327 0.131 Bacteroidetes Uncl. "Porphyromonadaceae" dbj|AB702775.1| 0.0 Gram-negative bacterium cTPY-13; AY239461 0.606 1.14 0.61 100 0.16 0.23 50 1.52 0.65 100 1.57 1.16 75 0.011 0.905 Porphyromonadaceae bacterium C941; Bacteroidetes Uncl. "Porphyromonadaceae" dbj|AB702775.1| 0.0 JF803519 0.596 0.04 0.05 57 0.02 0.04 25 0.11 0.05 100 0.07 0.05 75 0.410 0.413

Deferribacteres Mucispirillum gb|JQ891435.1| 0.0 Flexistipes group bacterium HRI1cae; AF059187 0.972 0.17 0.37 43 0.00 0.00 0 0.00 0.00 0 0.00 0.00 0 0.186 NA Clostridiales bacterium oral taxon F32; VO026; Firmicutes Acetivibrio gb|GQ448052.1| 0.0 HM099644 0.870 0.50 0.37 100 0.01 0.01 25 0.01 0.02 40 0.02 0.05 25 0.010 1.000 Firmicutes Allobaculum gb|JQ893241.1| 0.0 sp. ID4; AY960571 0.985 0.00 0.00 0 0.00 0.00 0 0.07 0.10 60 0.11 0.09 75 NA 0.533 Firmicutes Anaerosporobacter gb|FJ880932.1| 0.0 bacterium NLAE-zl-C556; JQ608256 0.903 0.20 0.26 71 0.00 0.00 0 0.00 0.00 0 0.00 0.00 0 0.050 NA Eubacterium hadrum; type strain: DSM 3319; Firmicutes Anaerostipes gb|FJ881307.1| 0.0 FR749934 0.832 0.23 0.25 57 0.00 0.00 0 0.00 0.00 0 0.00 0.00 0 0.101 NA Anaerotruncus colihominis (T); 14565; Firmicutes Anaerotruncus gb|JQ891773.1| 1E-178 AJ315980 0.985 0.01 0.02 43 0.00 0.00 0 0.07 0.10 80 0.09 0.11 50 0.186 0.901

Firmicutes Anaerotruncus gb|JQ891988.1| 0.0 Anaerotruncus colihominis; HKU19; DQ002932 0.863 0.03 0.03 57 0.01 0.03 25 0.11 0.16 60 0.41 0.51 100 0.410 0.268 Firmicutes Blautia gb|JF258992.1| 0.0 bacterium NLAE-zl-C551; JQ608251 0.952 0.31 0.25 86 0.79 0.25 100 0.00 0.00 0 0.01 0.01 25 0.042 0.371 Firmicutes Blautia gb|GQ493551.1| 0.0 Blautia glucerasea (T); HFTH-1; AB439724 0.987 0.06 0.07 86 0.07 0.07 75 0.00 0.00 0 0.00 0.00 0 0.850 NA Firmicutes Blautia gb|EU772879.1| 0.0 Blautia sp. M25; HM626178 0.930 3.35 1.99 100 5.06 1.61 100 0.01 0.02 40 0.02 0.03 50 0.164 0.687 Firmicutes Blautia gb|HM124291.1| 0.0 butyrate-producing bacterium SR1/1; AY305321 0.874 0.41 0.19 100 0.55 0.20 100 0.04 0.05 60 0.23 0.12 100 0.230 0.019

©2014 American Diabetes Association. Published online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db13-1526/-/DC1 SUPPLEMENTARY DATA

Lachnospiraceae bacterium DJF_RP14; Firmicutes Blautia gb|EU772879.1| 0.0 EU728751 0.936 0.53 0.59 86 0.81 0.33 100 0.00 0.00 0 0.00 0.00 0 0.230 NA Firmicutes Blautia gb|HQ804988.1| 0.0 Ruminococcus schinkii (T); Bie 41; X94964 0.898 0.24 0.28 86 0.22 0.21 75 0.00 0.00 0 0.01 0.02 25 0.850 0.371 Firmicutes Blautia gb|FJ881025.1| 0.0 Ruminococcus sp. DJF_VR67; EU728791 0.891 0.53 0.60 100 0.14 0.13 100 0.39 0.25 80 1.17 0.55 100 0.073 0.111 Firmicutes Blautia gb|JF260206.1| 0.0 Ruminococcus sp. M-1; AB125231 1.000 0.47 0.32 100 1.28 0.48 100 0.04 0.04 60 0.04 0.04 75 0.024 0.901 Firmicutes Clostridium IV gb|FJ880059.1| 0.0 bacterium NLAE-zl-C231; JQ608310 0.743 0.02 0.02 71 0.00 0.00 0 0.15 0.21 60 0.15 0.17 75 0.050 0.901 Firmicutes Clostridium IV gb|HM848627.1| 0.0 (T); DSM 753T; AJ305238 0.841 0.20 0.10 100 0.16 0.17 75 0.09 0.08 80 0.13 0.12 100 0.527 0.905 Firmicutes Clostridium IV dbj|AB506382.1| 0.0 Clostridium sp. BS-1; FJ805840 0.781 0.07 0.06 86 0.11 0.08 75 0.04 0.05 60 0.06 0.07 50 0.344 0.701 Firmicutes Clostridium IV gb|HQ805671.1| 0.0 Clostridium sp. Culture Jar-13; AB622826 0.847 0.02 0.03 29 0.00 0.00 0 0.12 0.10 100 0.06 0.03 100 0.327 0.556 Firmicutes Clostridium IV gb|GU959097.1| 0.0 Clostridium sp. YIT 12069; AB491207 0.676 0.15 0.16 57 0.02 0.04 25 0.98 0.79 100 0.26 0.33 50 0.216 0.110 Firmicutes Clostridium IV gb|GQ492087.1| 0.0 Clostridium sp. YIT 12070; AB491208 1.000 0.14 0.07 100 0.06 0.02 100 0.08 0.10 60 0.10 0.08 100 0.073 0.389 Clostridium viride (T); T2-7 (DSM 6836); Firmicutes Clostridium IV gb|JQ084713.1| 0.0 X81125 0.843 0.25 0.09 100 0.11 0.10 100 1.49 0.26 100 0.33 0.19 100 0.073 0.016 Firmicutes Clostridium IV gb|HM124074.1| 0.0 Eubacterium siraeum; 70/3; EU266550 0.825 0.12 0.25 43 0.00 0.00 0 0.00 0.00 0 0.00 0.00 0 0.186 NA Firmicutes Clostridium IV gb|GU959458.1| 0.0 bacterium 19gly4; AF550610 0.722 8.66 2.58 100 3.27 4.22 75 0.00 0.00 0 0.90 1.76 75 0.073 0.042 Firmicutes Clostridium sensu stricto gb|HQ782503.1| 0.0 bacterium FN062; AB298770 1.000 0.01 0.03 14 0.20 0.26 50 0.00 0.00 0 0.00 0.00 0 0.186 NA

Firmicutes Clostridium sensu stricto gb|JN885835.1| 0.0 (T); DSM 5521; Y18176 1.000 3.95 2.04 100 5.48 2.47 100 0.00 0.00 0 0.00 0.00 0 0.315 NA Clostridium sp. enrichment culture clone Y234; Firmicutes Clostridium sensu stricto gb|JN792362.1| 0.0 JF345341 0.868 0.02 0.03 43 0.18 0.10 100 0.00 0.00 0 0.00 0.00 0 0.016 NA Firmicutes Clostridium XI gb|JQ892143.1| 0.0 Clostridium ruminantium; LA1; EU089964 0.953 1.06 0.36 100 1.36 0.27 100 0.00 0.00 0 0.00 0.00 0 0.315 NA Firmicutes Clostridium XlVa gb|GU959587.1| 0.0 bacterium NLAE-zl-P613; JQ607197 0.799 0.26 0.25 71 0.00 0.00 0 0.83 0.43 100 0.00 0.00 0 0.050 0.015

Firmicutes Clostridium XlVa gb|JQ891394.1| 0.0 butyrate-producing bacterium M62/1; AY305309 0.914 2.55 1.03 100 3.44 1.52 100 4.14 1.59 100 5.38 2.58 100 0.315 0.730 Firmicutes Clostridium XlVa gb|GU959587.1| 0.0 Clostridiaceae bacterium SK082; AB298754 0.829 1.15 1.12 71 0.00 0.00 0 4.06 2.17 100 0.00 0.00 0 0.050 0.015 Firmicutes Clostridium XlVa gb|FJ881247.1| 0.0 Clostridium asparagiforme (T); N6; AJ582080 0.859 0.76 0.68 71 0.00 0.00 0 0.00 0.00 0 0.00 0.00 0 0.050 NA Clostridium glycyrrhizinilyticum (T); ZM35; Firmicutes Clostridium XlVa gb|JF243922.1| 0.0 AB233029 0.662 0.01 0.03 29 0.00 0.00 0 0.13 0.11 100 0.00 0.00 0 0.327 0.015 Firmicutes Clostridium XlVa gb|JQ608200.1| 0.0 Clostridium hathewayi; AY552788 0.968 0.02 0.05 14 0.03 0.04 50 0.05 0.08 40 0.13 0.13 75 0.400 0.443 (T); CCRI-9842; Firmicutes Clostridium XlVa gb|JQ820141.1| 0.0 EF564277 1.000 0.18 0.22 86 0.20 0.25 75 0.16 0.08 100 0.14 0.12 75 0.570 0.905 Firmicutes Clostridium XlVa gb|HQ792005.1| 0.0 Clostridium leptum; 10900; AF262239 0.909 0.20 0.25 86 0.38 0.30 100 0.13 0.18 60 0.64 0.63 100 0.230 0.065 Firmicutes Clostridium XlVa gb|HQ791726.1| 0.0 Clostridium nexile (T); DSM 1787; X73443 0.959 0.66 0.54 86 2.03 0.70 100 0.00 0.00 0 0.00 0.00 0 0.024 NA Clostridium saccharolyticum (T); DSM 2544; Firmicutes Clostridium XlVa gb|GU959587.1| 1E-179 Y18185 0.818 0.25 0.47 57 0.00 0.00 0 1.28 0.82 100 0.00 0.00 0 0.101 0.015 ; JCM 10420 M-18; Firmicutes Clostridium XlVa gb|EU511662.1| 0.0 AB020729 0.881 0.01 0.03 29 0.00 0.00 0 0.47 0.41 80 0.00 0.00 0 0.327 0.044 Firmicutes Clostridium XlVa gb|JQ892151.1| 0.0 Clostridium sp. Culture-41; AB622820 0.848 0.48 0.16 100 1.06 0.66 100 2.53 0.80 100 2.94 0.58 100 0.164 0.413 Firmicutes Clostridium XlVa emb|X73449.1| 1E-174 Clostridium sp. Kas203-2; AB114230 0.797 0.14 0.17 71 0.00 0.00 0 0.00 0.00 0 0.00 0.00 0 0.050 NA Firmicutes Clostridium XlVa gb|EU509924.1| 0.0 Clostridium sp.; LIP5; Y12289 0.893 0.14 0.35 29 0.00 0.00 0 0.00 0.00 0 0.00 0.00 0 0.327 NA Firmicutes Clostridium XlVa gb|FJ880297.1| 0.0 Clostridium symbiosum; 69; EF025909 0.849 0.00 0.00 0 0.00 0.00 0 0.03 0.07 20 0.11 0.13 75 NA 0.227 Firmicutes Clostridium XlVa gb|JQ607604.1| 0.0 Clostridium symbiosum; REM001; EF442669 1.000 1.12 0.64 100 2.62 1.16 100 1.31 0.56 100 0.99 0.50 100 0.073 0.286 Firmicutes Clostridium XlVa gb|JF794951.1| 0.0 rumen bacterium NK4A66; GU124467 0.920 0.29 0.18 86 0.24 0.32 50 0.00 0.00 0 2.65 5.30 25 0.634 0.371 Firmicutes Clostridium XlVb gb|FJ880656.1| 2E-167 bacterium S130(2)-2; GU136556 0.727 0.01 0.02 29 0.00 0.00 0 0.00 0.00 0 0.21 0.09 100 0.327 0.011 Firmicutes Clostridium XlVb gb|FJ880656.1| 0.0 Clostridiales bacterium 21-4c; HQ452858 0.817 2.50 0.39 100 4.13 0.53 100 0.90 0.83 60 1.91 0.52 100 0.006 0.110 Clostridium lactatifermentans (T); G17; Firmicutes Clostridium XlVb gb|FJ880656.1| 1E-168 AY033434 0.778 0.06 0.04 71 0.14 0.04 100 0.03 0.03 60 0.09 0.04 100 0.018 0.065 Firmicutes Coprococcus gb|DQ777926.1| 0.0 butyrate-producing bacterium SL7/1; AY305312 0.874 0.02 0.03 43 0.06 0.07 75 0.06 0.04 80 0.06 0.11 50 0.276 0.533 Firmicutes Coprococcus gb|EU508827.1| 0.0 Clostridium sp. ID6; AY960572 0.887 0.00 0.00 0 0.00 0.00 0 0.00 0.00 0 0.01 0.03 25 NA 0.371 Firmicutes Coprococcus gb|JQ084127.1| 0.0 Coprococcus catus; GD/7; EU266552 0.820 0.00 0.00 0 0.00 0.00 0 0.17 0.07 100 0.05 0.09 50 NA 0.110 Firmicutes Coprococcus gb|JF255576.1| 0.0 Coprococcus catus; L8; AB361624 0.830 0.10 0.24 29 0.00 0.00 0 0.66 0.37 100 4.42 4.56 100 0.327 0.191 (T); ATCC 27759; Firmicutes Coprococcus gb|FJ880289.1| 0.0 EF031543 0.878 0.90 0.83 86 0.10 0.11 50 0.00 0.00 0 0.00 0.00 0 0.070 NA

©2014 American Diabetes Association. Published online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db13-1526/-/DC1 SUPPLEMENTARY DATA

Firmicutes Desulfonispora gb|GU959689.1| 0.0 Desulfonosporus sp. AAN04; AB436739 0.648 0.55 0.18 100 0.88 0.31 100 0.78 0.25 100 0.74 0.31 100 0.042 0.905

Firmicutes Dorea gb|FJ879722.1| 0.0 Clostridiaceae bacterium DJF_B063; EU728703 0.923 0.00 0.01 14 0.00 0.00 0 0.27 0.36 60 0.00 0.00 0 0.571 0.109 Eubacterium coprostanoligenes (T); HL; Firmicutes Eubacterium gb|GU959638.1| 0.0 HM037995 0.787 0.21 0.24 71 0.05 0.10 25 0.00 0.00 0 0.21 0.22 75 0.276 0.042 Clostridium orbiscindens (T); DSM 6740; Firmicutes Flavonifractor gb|JF258942.1| 0.0 Y18187 1.000 0.11 0.17 71 0.27 0.06 100 0.34 0.61 100 0.49 0.29 100 0.218 0.191 Firmicutes Flavonifractor gb|JF258942.1| 0.0 Flavonifractor plautii; AIP029.07; EU541439 0.983 0.55 0.69 86 1.09 0.29 100 0.35 0.33 100 0.53 0.23 100 0.073 0.191 Hydrogenoanaerobacterium saccharovorans Firmicutes Hydrogenoanaerobacterium dbj|AB702849.1| 0.0 (T); SW512; EU158190 0.751 0.04 0.06 43 0.05 0.05 75 1.05 1.24 100 0.05 0.05 75 0.766 0.191 Firmicutes Lachnospiracea_incertae_sedis gb|HQ770584.1| 0.0 Clostridium sp. cTPY-17; AY239462 0.956 0.11 0.08 86 0.26 0.08 100 0.04 0.04 60 0.25 0.16 100 0.012 0.019 Firmicutes Lachnospiracea_incertae_sedis gb|HQ785850.1| 0.0 Clostridium sp. ID5; AY960574 0.955 0.23 0.20 86 0.24 0.20 100 0.03 0.04 40 0.10 0.17 50 0.788 0.893 Ruminococcus gnavus (T); ATCC 29149; Firmicutes Lachnospiracea_incertae_sedis gb|HQ814441.1| 0.0 X94967 0.939 0.14 0.14 86 0.97 0.77 100 0.00 0.00 0 0.00 0.00 0 0.024 NA Ruminococcus torques (T); ATCC 27756; Firmicutes Lachnospiracea_incertae_sedis gb|HQ792300.1| 0.0 L76604 0.925 0.65 0.48 100 0.99 0.74 100 0.00 0.00 0 0.00 0.00 0 0.412 NA Firmicutes Lactobacillus gb|JQ894318.1| 0.0 Lactobacillus murinus; ONS2; AY324630 1.000 0.09 0.10 71 0.24 0.24 75 0.04 0.06 40 0.03 0.02 75 0.391 1.000 Firmicutes Lactobacillus gb|JQ892923.1| 0.0 Lactobacillus sp. L-YJ; AY157573 1.000 0.04 0.04 57 0.05 0.07 50 0.00 0.00 0 0.08 0.12 50 1.000 0.131 Lactococcus lactis subsp. lactis; ZG7-10; Firmicutes Lactococcus gb|JQ754446.1| 0.0 HE646430 0.993 0.04 0.06 57 0.07 0.06 75 0.06 0.07 80 0.03 0.03 50 0.439 0.709 Firmicutes Oribacterium dbj|AB702893.1| 1E-118 Oribacterium sp. OBRC12; HQ616355 0.782 0.00 0.00 0 0.00 0.00 0 0.06 0.14 20 0.00 0.00 0 NA 0.502 Firmicutes Oscillibacter gb|JQ892723.1| 0.0 Oscillibacter sp. G2; HM626173 0.850 0.35 0.45 71 0.00 0.00 0 1.57 0.39 100 0.00 0.00 0 0.050 0.015

Firmicutes Oscillibacter gb|EF436308.2| 0.0 Oscillibacter valericigenes Sjm18-20; AP012044 0.832 0.08 0.11 43 0.05 0.07 50 0.00 0.00 0 0.25 0.14 100 0.918 0.011 Firmicutes Oscillibacter gb|HM124080.1| 0.0 Oscillospira guilliermondii; OSC4; AB040498 0.838 0.15 0.20 86 0.00 0.00 0 1.08 1.03 80 0.23 0.26 100 0.023 0.413 Oscillospiraceae bacterium AIP 1035.11; Firmicutes Oscillibacter emb|FP083032.1| 0.0 JQ246091 0.873 0.01 0.01 29 0.01 0.01 25 0.00 0.00 0 0.09 0.05 100 1.000 0.011 Oscillospiraceae bacterium NML 061048; Firmicutes Oscillibacter gb|HQ790721.1| 0.0 EU149939 0.813 1.12 0.71 86 0.52 0.45 75 0.16 0.09 100 0.60 0.62 100 0.130 0.413 Peptococcus sp. canine oral taxon 344; 1O039; Firmicutes Peptococcus gb|HQ789613.1| 0.0 JN713513 0.673 1.67 0.23 100 2.11 0.72 100 2.43 0.52 100 1.88 0.48 100 0.230 0.111 Firmicutes Pseudoflavonifractor gb|JQ892170.1| 0.0 bacterium ASF500; ASF 500; AF157051 0.951 2.66 1.29 100 0.75 0.49 100 4.89 1.26 100 9.72 4.82 100 0.012 0.016 Firmicutes Pseudoflavonifractor gb|JQ084092.1| 0.0 Clostridiales bacterium 53-4c; HQ452851 0.889 0.17 0.19 71 0.16 0.05 100 0.21 0.11 100 0.32 0.16 100 0.925 0.730 Firmicutes Pseudoflavonifractor gb|FJ880774.1| 0.0 Clostridium sp. NML 04A032; EU815224 0.745 0.00 0.01 14 0.02 0.04 25 0.00 0.00 0 0.13 0.15 75 0.674 0.042 Firmicutes Robinsoniella gb|GU959587.1| 7E-141 Clostridium sp. Clone-16; AB622836 0.718 0.01 0.01 29 0.00 0.00 0 0.16 0.13 80 0.00 0.00 0 0.327 0.044 Firmicutes Roseburia gb|DQ456475.1| 0.0 Roseburia faecis (T); M72/1; AY305310 0.982 0.61 0.26 100 0.70 0.64 100 1.27 0.29 100 0.31 0.42 75 0.927 0.032 Firmicutes Roseburia gb|JQ307268.1| 0.0 Roseburia intestinalis (T); L1-82; AJ312385 0.989 0.03 0.04 43 0.05 0.06 50 0.02 0.03 40 0.00 0.00 0 0.471 0.240 Firmicutes Roseburia gb|JQ891177.1| 0.0 Roseburia intestinalis; XB6B4; AM055815 0.817 0.00 0.00 0 0.00 0.00 0 0.16 0.12 80 0.64 0.60 100 NA 0.191 Firmicutes Ruminococcus gb|HQ785669.1| 0.0 Clostridiales bacterium 80/3; EU266551 0.880 1.04 0.65 86 0.00 0.00 0 0.00 0.00 0 0.00 0.00 0 0.023 NA Firmicutes Ruminococcus dbj|AB606289.1| 0.0 Ruminococcus bromii; X85099 0.917 0.28 0.26 86 0.07 0.08 50 0.36 0.27 100 0.62 0.59 100 0.105 0.730 Ruminococcus flavefaciens; 007; LRC017; Firmicutes Ruminococcus gb|GQ369777.1| 0.0 AF030447 0.966 5.96 2.71 100 1.20 2.00 50 0.00 0.00 0 1.15 2.31 25 0.029 0.371 Firmicutes Turicibacter gb|JQ893864.1| 0.0 Turicibacter sanguinis (T); AF349724 0.840 0.39 0.31 86 0.19 0.27 50 0.00 0.00 0 0.00 0.00 0 0.294 NA Uncl. Clostridiales_Incertae Sedis Peptostreptococcaceae bacterium canine oral Firmicutes XII gb|GU105102.1| 0.0 taxon 019; OB001; JN713180 0.501 0.00 0.00 0 0.00 0.00 0 0.04 0.07 40 0.02 0.03 25 NA 0.771 Firmicutes Uncl. Lachnospiraceae gb|JF794962.1| 0.0 bacterium CT-m2; HM989805 0.822 0.05 0.07 57 0.00 0.00 0 1.10 1.13 100 0.84 1.45 50 0.101 0.539 bacterium enrichment culture clone ecb12; Firmicutes Uncl. Lachnospiraceae gb|HQ786419.1| 3E-144 HQ395206 0.655 0.00 0.01 14 0.00 0.00 0 0.02 0.03 60 0.04 0.04 75 0.571 1.000 Firmicutes Uncl. Lachnospiraceae gb|HQ789605.1| 0.0 bacterium NLAE-zl-C545; JQ608245 0.976 0.05 0.09 29 0.01 0.01 25 0.01 0.03 20 0.12 0.10 75 0.810 0.081 Firmicutes Uncl. Lachnospiraceae gb|JF794908.1| 0.0 bacterium YE257; FJ966227 0.709 0.03 0.05 43 0.00 0.00 0 0.14 0.10 80 0.02 0.03 50 0.186 0.105 Blautia sp. canine oral taxon 143; PP006; Firmicutes Uncl. Lachnospiraceae gb|JN713310.1| 0.0 JN713310 0.959 0.13 0.15 71 0.37 0.28 75 0.00 0.00 0 0.00 0.00 0 0.215 NA

©2014 American Diabetes Association. Published online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db13-1526/-/DC1 SUPPLEMENTARY DATA

Butyrivibrio crossotus; type strain: DSM2876; Firmicutes Uncl. Lachnospiraceae gb|JQ084267.1| 0.0 FR733670 0.883 0.92 1.16 57 0.00 0.00 0 0.00 0.00 0 0.00 0.00 0 0.101 NA Firmicutes Uncl. Lachnospiraceae gb|HQ765927.1| 0.0 Clostridiaceae bacterium FH052; AB298768 0.784 0.02 0.06 14 0.00 0.00 0 0.00 0.00 0 0.00 0.00 0 0.571 NA Firmicutes Uncl. Lachnospiraceae gb|HQ786419.1| 0.0 Clostridiales bacterium APP2; GQ863487 0.654 0.06 0.08 71 0.01 0.03 25 0.22 0.09 100 0.13 0.06 100 0.276 0.191 Firmicutes Uncl. Lachnospiraceae gb|AY990989.1| 4E-179 Clostridium sp. ASF502; ASF 502; AF157053 0.959 0.00 0.00 0 0.00 0.00 0 0.04 0.03 80 0.01 0.03 25 NA 0.201 Firmicutes Uncl. Lachnospiraceae gb|EF097418.1| 0.0 Clostridium sp. Clone-17; AB622837 0.917 0.00 0.00 0 0.00 0.00 0 0.67 0.27 100 0.43 0.23 100 NA 0.413 Firmicutes Uncl. Lachnospiraceae gb|FJ683052.1| 0.0 Clostridium sp. Clone-7; AB622834 0.928 0.07 0.07 86 0.08 0.06 100 0.23 0.12 100 1.53 1.58 100 0.649 0.016 Firmicutes Uncl. Lachnospiraceae gb|FJ880972.1| 0.0 Clostridium sp. Culture-54; AB622823 0.932 0.01 0.02 14 0.00 0.00 0 0.00 0.00 0 0.00 0.00 0 0.571 NA Firmicutes Uncl. Lachnospiraceae gb|FJ880915.1| 0.0 intestinal bacterium CG19-1; FJ711049 0.842 0.01 0.03 29 0.00 0.00 0 1.16 0.60 100 0.13 0.09 100 0.327 0.016 Firmicutes Uncl. Lachnospiraceae gb|GQ298173.1| 0.0 Lachnospiraceae bacterium 14-2; DQ789124 0.934 0.04 0.07 43 0.00 0.00 0 0.06 0.04 100 0.00 0.00 0 0.186 0.015 Firmicutes Uncl. Lachnospiraceae gb|JQ891326.1| 0.0 Lachnospiraceae bacterium 607; AB700365 0.855 0.23 0.58 29 0.00 0.00 0 0.00 0.00 0 0.00 0.00 0 0.327 NA Firmicutes Uncl. Lachnospiraceae dbj|AB700360.1| 0.0 Lachnospiraceae bacterium A2; DQ789117 1.000 0.00 0.00 0 0.01 0.01 25 0.00 0.00 0 0.62 0.31 100 0.257 0.011 Firmicutes Uncl. Lachnospiraceae gb|EU622771.1| 0.0 Lachnospiraceae bacterium A4; DQ789118 0.828 0.11 0.11 71 0.00 0.00 0 0.00 0.00 0 0.01 0.03 25 0.050 0.371 Firmicutes Uncl. Lachnospiraceae gb|GQ493579.1| 0.0 Ruminococcus sp. YE58; AY442822 0.909 0.28 0.16 100 0.46 0.15 100 0.01 0.03 20 0.07 0.07 75 0.164 0.140 Clostridiaceae bacterium NML 060002; Firmicutes Uncl. gb|FJ878981.1| 0.0 EU815225 0.730 0.06 0.04 86 0.09 0.10 50 0.15 0.09 100 0.15 0.11 75 0.924 0.730 Clostridiaceae bacterium NML 061030; Firmicutes Uncl. Ruminococcaceae gb|JN713248.1| 0.0 EU183300 0.997 0.61 0.68 86 0.30 0.10 100 0.64 0.29 100 1.23 1.56 100 0.927 0.905 Firmicutes Uncl. Ruminococcaceae gb|JQ084116.1| 0.0 Clostridiales bacterium 30-4c; HQ452853 0.880 0.49 0.44 86 0.36 0.37 75 0.03 0.07 20 0.83 0.06 100 0.449 0.015 Clostridiales bacterium canine oral taxon 061; Firmicutes Uncl. Ruminococcaceae gb|FJ880909.1| 0.0 OF002; JN713225 0.830 0.00 0.01 14 0.02 0.04 25 0.00 0.00 0 0.20 0.10 100 0.674 0.011 Firmicutes Uncl. Ruminococcaceae gb|GU958847.1| 0.0 Clostridium sp. Culture-1; AB622814 0.960 0.46 0.82 71 0.00 0.00 0 7.11 1.64 100 0.01 0.01 50 0.050 0.019 Firmicutes Uncl. Ruminococcaceae gb|FJ880287.1| 0.0 rumen bacterium NK4A214; GU324404 0.906 0.76 0.21 100 0.14 0.20 75 0.00 0.00 0 0.69 0.23 100 0.006 0.011 Firmicutes Uncl. Firmicutes dbj|AB606234.1| 0.0 bacterium NLAE-zl-C589; JQ608288 0.808 0.01 0.03 14 0.00 0.00 0 0.00 0.00 0 0.86 1.35 100 0.571 0.011 Firmicutes Uncl. Firmicutes gb|JF172118.1| 0.0 Christensenella minuta; YIT 12065; AB490809 0.652 0.04 0.05 57 0.00 0.00 0 0.01 0.02 40 0.02 0.02 50 0.101 0.893 Firmicutes Uncl. Firmicutes gb|HQ814888.1| 0.0 Eubacterium desmolans (T); L34618 0.855 0.10 0.11 57 0.08 0.09 100 0.00 0.00 0 0.03 0.06 25 0.924 0.371 Peptostreptococcaceae bacterium canine oral Firmicutes Uncl. Firmicutes dbj|AB626919.1| 0.0 taxon 333; 1G023; JN713503 0.848 0.16 0.15 86 0.01 0.01 25 0.05 0.10 40 0.27 0.24 100 0.053 0.062 Proteobacteria Escherichia/Shigella gb|HQ771207.1| 0.0 Escherichia coli; 228; EF560774 0.997 0.04 0.04 57 0.50 0.32 100 0.00 0.00 0 0.00 0.00 0 0.010 NA Proteobacteria Escherichia/Shigella gb|HQ759058.1| 0.0 Escherichia coli; 4090; FJ463818 0.992 0.03 0.04 43 0.28 0.15 100 0.00 0.00 0 0.02 0.05 25 0.016 0.371 Proteobacteria Escherichia/Shigella gb|JX040337.1| 0.0 Escherichia coli; PK3; X80731 1.000 0.08 0.08 71 1.05 0.81 100 0.00 0.00 0 0.00 0.00 0 0.018 NA Insolitispirillum peregrinum subsp. integrum; Proteobacteria Insolitispirillum gb|JF260247.1| 0.0 IAM 14946; AB074521 0.596 0.23 0.28 71 0.04 0.07 25 0.89 0.34 100 0.38 0.20 100 0.198 0.063 Proteobacteria Kiloniella gb|JF260740.1| 0.0 Thalassospira sp. 2ta1; FJ952805 0.526 0.51 0.70 71 0.00 0.00 0 0.00 0.00 0 0.00 0.00 0 0.050 NA Parasutterella excrementihominis (T); YIT Proteobacteria Parasutterella gb|HQ774176.1| 0.0 11859; AB370250 1.000 1.26 0.49 100 3.17 0.77 100 1.86 0.80 100 2.11 0.29 100 0.006 0.905 Verrucomicrobia Akkermansia gb|HQ793323.1| 0.0 Akkermansia muciniphila (T); Muc; AY271254 0.968 0.01 0.01 29 0.02 0.03 25 0.06 0.06 80 0.02 0.03 50 0.105 0.730 unclassified_Bact eria Uncl. gb|GU959660.1| 0.0 bacterium YE57; AY442821 0.848 0.11 0.13 100 0.03 0.05 25 0.25 0.14 100 0.33 0.27 100 0.391 0.371 unclassified_Bact eria Uncl. Bacteria gb|GU958610.1| 0.0 rumen bacterium R-7; AB239481 0.794 1.58 0.86 86 0.79 1.56 50 0.00 0.00 0 0.63 1.27 25 1.000 0.383

©2014 American Diabetes Association. Published online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db13-1526/-/DC1 SUPPLEMENTARY DATA

Supplementary Figure 1. Variable importance for OP versus OR on either a chow or HF‐diet by supervised classification with random forest classifier analysis. Main predictive genera for each group of animals are observed on the top of the chart, with accuracy of predication decreasing down the genera column.

Variable importance for OP vs. OR Chow HF‐diet

Flavonifractor unclassified_Ruminococcaceae Clostridium_XlVb unclassified_Porphyromonadaceae Johnsonella Clostridium_XlVb unclassified_Clostridiales Escherichia/Shigella Lachnospiracea_incertae_sedis Parasutterella Escherichia/Shigella Clostridium_XlVa Lactobacillus Alistipes Pasteurella Syntrophococcus Bacteroides Parabacteroides Enterococcus Insolitispirillum unclassified_Clostridiales Anaerovorax Oscillibacter Desulfonispora Clostridium_IV Parasutterella unclassified_Bacteria Parasporobacterium Clostridium_XI Acetivibrio Ruminococcus Acinetobacter Acetivibrio Adlercreutzia Kiloniella Aeromonas unclassified_Lachnospiraceae Akkermansia Erysipelotrichaceae_incertae_sedis Alkaliphilus Adlercreutzia Anaeroplasma Butyricicoccus Asaccharobacter Peptococcus Bifidobacterium Pseudoflavonifractor Butyrivibrio Barnesiella Caloramator Blautia Clostridium_IV Proteus Clostridium_XII Lactobacillus Clostridium_XVIII Eubacterium Coprobacillus Acetanaerobacterium

0123 01234 MeanDecreaseAccuracy MeanDecreaseAccuracy

©2014 American Diabetes Association. Published online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db13-1526/-/DC1 SUPPLEMENTARY DATA

Supplementary Figure 2. OP rats exhibit increased weight gain, adiposity and adiposity hormones during HF‐feeding (data related to Fig. 1 and Fig. 2, main text). (A) Body weight of OP and OR rats during 12wks of HF‐feeding. (B) Adiposity index, (C) daily food intake, and D) circulating plasma levels of leptin and insulin after brief 5hr fast in OP and OR rats. Data are expressed as mean ± SEM. **P < 0.01, ***P < 0.0001.

©2014 American Diabetes Association. Published online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db13-1526/-/DC1 SUPPLEMENTARY DATA

Supplementary Figure 3. During HF‐feeding, OP rats and GF recipients have altered lipid profile, and reductions in proteins involved in intestinal satiety signaling (Supplementary data related to Fig. 2, main text). (A) Lipid profile of donor OP and OR rats. (B) Lipid profile of CVOP and CVOR animals after brief fast. (C) Plasma GLP‐1 and PYY. (D) Intestinal protein expression of gut peptides in donors and recipient mice. (E‐F) mRNA transcript of OP and OR rats, and protein expression of GPRs in intestinal epithelial cells of donor rats and recipient mice. Data are expressed as mean ± SEM. *P < 0.05, **P < 0.01, ***P < 0.0001. † denotes significant difference from chow‐fed diet condition within phenotype, †P < 0.05, ††P < 0.01, †††P < 0.0001.

©2014 American Diabetes Association. Published online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db13-1526/-/DC1 SUPPLEMENTARY DATA

Supplementary Figure 4. OP rats exhibit increases in lipid storage via enhanced lipogenesis and fatty‐ acid transporters in both liver and adipose tissue compared to OR rats during HF‐feeding (data related to Fig. 3, main text). (A) Liver and adipose tissue protein expression of lipogenic and adipogenic enzymes in OP and OR rats during HF‐feeding (B) Ratio of phosphorylated to total ACC in liver and adipose. (C) Western blots of fatty‐acid transporters, CD36 and FABP. Data are expressed as mean ± SEM. *P < 0.05, **P < 0.01, ***P < 0.0001.

©2014 American Diabetes Association. Published online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db13-1526/-/DC1 SUPPLEMENTARY DATA

Supplementary Figure 5. HF‐feeding results in increased gut permeability and systemic inflammation in OP rats (data related to Fig. 4, main text). A) Protein expression of tight junction proteins, ZO‐1, occluding, and phosphyorylated‐MLC, in the distal intestine of donor rats on HF‐diet. (B) Circulating inflammatory markers in OP and OR rats after 5hr fast. Data are expressed as mean ± SEM. *P < 0.05, **P < 0.01, ***P < 0.0001.

©2014 American Diabetes Association. Published online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db13-1526/-/DC1 SUPPLEMENTARY DATA

Supplementary Figure 6. HF‐fed OP rats have increased inflammatory signaling in liver and adipose tissue (data related to Fig. 5, main text). (A‐B) Gene expression of inflammatory cytokines in liver and adipose tissue. (C) TLR4 gene expression in liver and adipose tissue. (D) NF‐κB/IKKβ inflammatory signaling pathway of OP and OR rats depicted by western blots. Data are expressed as mean ± SEM. *P < 0.05, **P < 0.01, ***P < 0.0001.

©2014 American Diabetes Association. Published online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db13-1526/-/DC1 SUPPLEMENTARY DATA

Supplementary Figure 7. Variable importance for CVOP versus CVOR maintained on HF‐diet by supervised classification with random forest classifier analysis. Main predictive genera for each group of animals are observed on the top of the chart, with accuracy of predication decreasing down the genera column.

Variable importance for CVOP vs CVOR

Pseudoflavonifractor unclassified_Ruminococcaceae Robinsoniella Lachnospiracea_incertae_sedis Clostridium_IV Clostridium_XlVb Oscillibacter Blautia Eubacterium Insolitispirillum Coprococcus Flavonifractor Bacteroides Barnesiella Prevotella unclassified_Porphyromonadaceae Dorea Lactobacillus Parasutterella Alistipes Hydrogenoanaerobacterium Parabacteroides Porphyromonas Mucispirillum Allobaculum Anaerosporobacter Anaerostipes Clostridium_sensu_stricto Clostridium_XI Clostridium_XlVa Oribacterium Turicibacter Escherichia_Shigella Kiloniella Roseburia Akkermansia Anaerotruncus Coriobacterineae Ruminococcus unclassified_Clostridiales_Incertae_Sedis_XII unclassified_Lachnospiraceae Acetivibrio Peptococcus Desulfonispora Lactococcus

-101234 MeanDecreaseAccuracy

©2014 American Diabetes Association. Published online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db13-1526/-/DC1