Abstract

Background Pathogenesis of inflammatory bowel disease (IBD) is influenced by differences in the function of gut microbiota. Bile acid (BA) metabolism is carried out in the gastrointestinal tract mainly by three bacterial enzymes. These include a bile acid hydrolase (BSH) that deconjugates BA, as well as two enzymes producing secondary BA: a hydroxysteroid dehydrogenase (HSDH) and an alpha-dehydroxylase (ADH). BA metabolizing-microbiota (BAMM) has been demonstrated to influence host homeostasis and inflammation of the gut, but there is scarce evidence of its role in IBD Aims To evaluate if mucosal BAMM abundance is related to endoscopic inflammation in IBD patients Methods Ulcerative colitis (UC), IBD unclassified (IBDU), Crohn’s disease (CD) patients and healthy controls (HC) undergoing colonoscopy were recruited. Microbial DNA from terminal ileum (TI) and sigmoid colon (SC) biopsies was extracted and the 16s rRNA gene was sequenced. BAMM gene function was inferred with PICRUSt from 9000 sequences/sample using the following Clusters of Orthologous Groups (COGs): COG3049 for BSH; COG1902 for HSDH and COG1062 for ADH. Abundance of these microbial genes was compared with endoscopic inflammation using the segmental simple endoscopic score (sSES-CD) and segmental Mayo endoscopic score (sMES) in CD and UC/IBDU patients, respectively. An sSES-CD and sMES of 0–2 and 0–1, respectively, were considered indicative of non-inflamed tissue. Clinical data were obtained and users of antibiotics before colonoscopy were excluded. Non-parametric tests and false discovery correction were used in this study Results A total of 436 samples (TI=183 and SC=253) from 260 subjects were analyzed. The mean age of all included subjects was 37.01 ± 14.3 years, 46.3% were female, 37% CD, 43% UC/IBDU and 20% HC. Non-inflamed tissue was observed in 66% of TI and 38% of SC from IBD patients, as well as all HC samples (TI=33 and SC=51). Overall, there was no difference in BSH, HSDH and ADH gene abundance when comparing non-inflamed TI and non-inflamed SC. Comparison of non-inflamed tissue (TI vs SC) within HC, CD and UC/IBDU patients did not show a significant difference. When we compared inflamed and non-inflamed tissues within different groups and sites, only one significant increase of ADH gene abundance (COG1062) was noted in TI from CD patients, after Benjamini-Hochberg correction (Q-value=0.049, figure) Conclusions Differences in inferred mucosal BAMM might be associated with tissue inflammation in IBD patients. Specifically, BA-dehydroxylating bacterial genes are increased in inflamed TI from CD patients suggesting a potential role of this microbiota function in IBD