Increased Primary Bile Acids with Ileocolonic Resection Impact Ileal Inflammation and Gut Microbiota in Inflammatory Bowel Disease

Abstract Background Most Crohn’s disease [CD] patients require surgery. Ileitis recurs after most ileocolectomies and is a critical determinant for outcomes. The impacts of ileocolectomy-induced bile acid [BA] perturbations on intestinal microbiota and inflammation are unknown. We characterized the...

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Published in:Journal of Crohn's and colitis 2023-05, Vol.17 (5), p.795-803
Main Authors: Battat, Robert, Scherl, Ellen J, Lukin, Dana, Charilaou, Paris, Mahtani, Prerna, Gerber, Juliette, Gandara, Jorge A, Dündar, Friederike, Zumbo, Paul, Betel, Doron, Guo, Chun-Jun, Longman, Randy S
Format: Article
Language:English
Subjects:
Bile Acids and Salts
Colectomy
Gastrointestinal Microbiome
Humans
Ileitis - microbiology
Ileitis - surgery
Inflammation
Inflammatory Bowel Diseases - microbiology
Inflammatory Bowel Diseases - surgery
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Summary:Abstract Background Most Crohn’s disease [CD] patients require surgery. Ileitis recurs after most ileocolectomies and is a critical determinant for outcomes. The impacts of ileocolectomy-induced bile acid [BA] perturbations on intestinal microbiota and inflammation are unknown. We characterized the relationships between ileocolectomy, stool BAs, 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 was use to profile microbial composition and function. Relationships between ileocolectomy, BAs and microbiota were assessed. Results In 166 patients, elevated primary and secondary BAs existed with ileocolectomy. With ileitis, only primary BAs [795 vs 398 nmol/g, p = 0.009] were higher compared to without ileitis. The optimal primary BA threshold [≥228 nmol/g] identified ileitis on multivariable analysis [odds ratio = 2.3, p = 0.04]. Microbial diversity, Faecalibacterium prausnitzii and O-acetylhomoserine aminocarboxypropyltransferase [MetY] were decreased with elevated primary BAs. Amongst ileocolectomy patients, only those with elevated primary BAs had diversity, F. prausnitzii and MetY reductions. Those with both ileocolectomy and intermediate [p = 0.002] or high [≥228 nmol/g, p = 9.1e-11]] primary BA concentrations had reduced F. prausnitzii compared to without ileocolectomy. Those with ileocolectomy and low [
ISSN:1873-9946
1876-4479
DOI:10.1093/ecco-jcc/jjac173