Gut microbial metabolome in inflammatory bowel disease: From association to therapeutic perspectives

Abstract

Inflammatory bowel disease (IBD), comprising Crohn's disease (CD) and ulcerative colitis (UC), is a set of clinically chronic, relapsing gastrointestinal inflammatory disease and lacks of an absolute cure. Although the precise etiology is unknown, developments in high-throughput microbial genomic sequencing significantly illuminate the changes in the intestinal microbial structure and functions in patients with IBD. The application of microbial metabolomics suggests that the microbiota can influence IBD pathogenesis by producing metabolites, which are implicated as crucial mediators of host-microbial crosstalk. This review aims to elaborate the current knowledge of perturbations of the microbiome-metabolome interface in IBD with description of altered composition and metabolite profiles of gut microbiota. We emphasized and elaborated recent findings of several potentially protective metabolite classes in IBD, including fatty acids, amino acids and derivatives and bile acids. This article will facilitate a deeper understanding of the new therapeutic approach for IBD by applying metabolome-based adjunctive treatment.

Keywords: AMPs, Antimicrobial peptides; BAs, Bile acids; BC, Bray Curtis; CD, Crohn’s disease; CDI, Clostridioides difficile infection; DC, Diversion colitis; DCA, Deoxycholic acid; DSS, Dextran sulfate sodium; FAs, Fatty acid; FMT, Fecal microbiota transplantation; FODMAP, Fermentable oligosaccharide, disaccharide, monosaccharide, and polyol; GC–MS, Gas chromatography-mass spectrometry; Gut microbiota; HDAC, Histone deacetylase; IBD, Inflammatory bowel disease; Inflammatory bowel diseases; LC-MS, Liquid chromatography-mass spectrometry; LCA, Lithocholic acid; LCFAs, Long-chain fatty acids; MCFAs, Medium-chain fatty acids; MD, Mediterranean diet; MS, Mass spectrometry; Metabolite; Metabolomics; Metagenomics; Microbial therapeutics; NMR, Nuclear magnetic resonance; PBAs, Primary bile acids; SBAs, Secondary bile acids; SCD, Special carbohydrate diet; SCFAs, Short-chain fatty acids; TNBS, 2,4,6-trinitro-benzene sulfonic acid; UC, Ulcerative colitis; UDCA, Ursodeoxycholic acid; UPLC-MS, ultraperformance liquid chromatography coupled to mass spectrometry; UU, Unweighted UniFrac; WMS, Whole-metagenome shotgun.

Graphical abstract