PMID- 25517115 OWN - NLM STAT- MEDLINE DCOM- 20160112 LR - 20181113 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 9 IP - 12 DP - 2014 TI - Bacterial bile metabolising gene abundance in Crohn's, ulcerative colitis and type 2 diabetes metagenomes. PG - e115175 LID - 10.1371/journal.pone.0115175 [doi] LID - e115175 AB - We performed an analysis to determine the importance of bile acid modification genes in the gut microbiome of inflammatory bowel disease and type 2 diabetic patients. We used publicly available metagenomic datasets from the Human Microbiome Project and the MetaHIT consortium, and determined the abundance of bile salt hydrolase gene (bsh), 7 alpha-dehydroxylase gene (adh) and 7-alpha hydroxysteroid dehydrogenase gene (hsdh) in fecal bacteria in diseased populations of Crohn's disease (CD), Ulcerative Colitis (UC) and Type 2 diabetes mellitus (T2DM). Phylum level abundance analysis showed a significant reduction in Firmicute-derived bsh in UC and T2DM patients but not in CD patients, relative to healthy controls. Reduction of adh and hsdh genes was also seen in UC and T2DM patients, while an increase was observed in the CD population as compared to healthy controls. A further analysis of the bsh genes showed significant differences in the correlations of certain Firmicutes families with disease or healthy populations. From this observation we proceeded to analyse BSH protein sequences and identified BSH proteins clusters representing the most abundant strains in our analysis of Firmicute bsh genes. The abundance of the bsh genes corresponding to one of these protein clusters was significantly reduced in all disease states relative to healthy controls. This cluster includes bsh genes derived from Lachospiraceae, Clostridiaceae, Erysipelotrichaceae and Ruminococcaceae families. This metagenomic analysis provides evidence of the importance of bile acid modifying enzymes in health and disease. It further highlights the importance of identifying gene and protein clusters, as the same gene may be associated with health or disease, depending on the strains expressing the enzyme, and differences in the enzymes themselves. FAU - Labbe, Alain AU - Labbe A AD - Micropharma Limited, Montreal, Quebec, Canada. FAU - Ganopolsky, Jorge G AU - Ganopolsky JG AD - Micropharma Limited, Montreal, Quebec, Canada. FAU - Martoni, Christopher J AU - Martoni CJ AD - Micropharma Limited, Montreal, Quebec, Canada. FAU - Prakash, Satya AU - Prakash S AD - Biomedical Technology and Cell Therapy Research Laboratory, Department of Biomedical Engineering, Faculty of Medicine, Montreal, Quebec, Canada; Micropharma Limited, Montreal, Quebec, Canada. FAU - Jones, Mitchell L AU - Jones ML AD - Biomedical Technology and Cell Therapy Research Laboratory, Department of Biomedical Engineering, Faculty of Medicine, Montreal, Quebec, Canada; Micropharma Limited, Montreal, Quebec, Canada. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20141217 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Bile Acids and Salts) RN - EC 1.1.- (Hydroxysteroid Dehydrogenases) RN - EC 1.1.1.159 (7 alpha-hydroxysteroid dehydrogenase) RN - EC 3.5.- (Amidohydrolases) RN - EC 3.5.1.24 (choloylglycine hydrolase) SB - IM MH - Amidohydrolases/genetics MH - Animals MH - Bacteria/enzymology MH - Bile Acids and Salts/*metabolism MH - Colitis, Ulcerative/*enzymology/genetics/microbiology MH - Crohn Disease/*enzymology/genetics/microbiology MH - Databases, Factual MH - Diabetes Mellitus, Type 2/*enzymology/genetics/microbiology MH - Feces/enzymology/microbiology MH - Gastrointestinal Tract/*enzymology/microbiology MH - Genes, Bacterial/*genetics MH - Humans MH - Hydroxysteroid Dehydrogenases/genetics MH - *Metagenome MH - Metagenomics MH - Mice MH - Microbiota MH - Phylogeny PMC - PMC4269443 COIS- Competing Interests: Micropharma Limited funded this research. MLJ and SP are co-founders and shareholders of Micropharma. MLJ, CJM, JGG and AL are employed by and CJM is a shareholder of Micropharma. AL, JGG and MLJ designed the research. AL collected and analyzed the data. AL, JGG, CJM and MLJ prepared the manuscript for publication. Micropharma Limited holds no editorial restriction over the work published and the authors' association with it does not alter their adherence to PLOS ONE policies on sharing data and materials. EDAT- 2014/12/18 06:00 MHDA- 2016/01/13 06:00 PMCR- 2014/12/17 CRDT- 2014/12/18 06:00 PHST- 2014/05/29 00:00 [received] PHST- 2014/11/19 00:00 [accepted] PHST- 2014/12/18 06:00 [entrez] PHST- 2014/12/18 06:00 [pubmed] PHST- 2016/01/13 06:00 [medline] PHST- 2014/12/17 00:00 [pmc-release] AID - PONE-D-14-24012 [pii] AID - 10.1371/journal.pone.0115175 [doi] PST - epublish SO - PLoS One. 2014 Dec 17;9(12):e115175. doi: 10.1371/journal.pone.0115175. eCollection 2014.