Increased Primary Bile Acids with Ileocolonic Resection Impact Ileal Inflammation and Gut Microbiota in Inflammatory Bowel Disease.
Academic Article
Overview
abstract
BACKGROUND: Most Crohn's disease (CD) patients require surgery. Ileitis recurs after most ileocolectomies and is a critical determinant for outcomes. The impact of ileocolectomy-induced bile acid (BA) perturbations on intestinal microbiota and inflammation are unknown. We characterized relationships between ileocolectomy, stool BA, microbiota, and intestinal inflammation in inflammatory bowel disease (IBD). METHODS: Validated IBD clinical and endoscopic assessments were prospectively collected. Stool primary and secondary BA concentrations were compared based on ileocolectomy and ileitis status. Primary BA thresholds for ileitis were evaluated. Metagenomic sequencing profiled microbial composition and function. Relationships between ileocolectomy, BA and microbiota were assessed. RESULTS: In 166 patients, elevated primary and secondary BA existed with ileocolectomy. With ileitis, only primary BA (795 nMol/g vs 398 nMol/g, p=0.009) were higher compared to without ileitis. The optimal primary BA threshold (≥228nMol/g) identified ileitis on multivariable analysis (OR=2.3, p=0.04). Microbial diversity, Faecalibacterium prausnitzii and O-acetylhomoserine aminocarboxypropyltransferase (MetY) were decreased with elevated primary BA. Amongst ileocolectomy patients, only those with elevated primary BA had diversity, F.prausnitzii and MetY reductions. Those with both ileocolectomy and intermediate (p=0.002) or high (≥228nMol/g, p=9.1e-11) ) primary BA had reduced F.prausnitzii compared to without ileocolectomy. Those with ileocolectomy and low (<29.2nMol/g) primary BA had similar F.prausnitzii as those without ileocolectomy (P=0.13). MetY was reduced with ileitis (p=0.02). CONCLUSIONS: Elevated primary bile acids were associated with ileitis, and reduced microbial diversity, F.prausnitzii abundance, and enzymatic abundance of MetY (acetate and L-methionine producing enzyme expressed by F.prausnitzii) and were the only factor associated with these findings after ileocolectomy.
