Abstract
Inflammatory bowel disease (IBD) is a chronic immune-mediated inflammatory disorder of the gastrointestinal tract that arises due to complex interactions between host genetic risk factors, environmental factors, and a dysbiotic gut microbiota. Although metagenomic approaches have attempted to characterise the dysbiosis occurring in IBD, the precise mechanistic pathways interlinking the gut microbiota and the intestinal mucosa are still yet to be unravelled. To deconvolute these complex interactions, a more reductionist approach involving microbial metabolites has been suggested. Bile acids have emerged as a key class of microbiota-associated metabolites that are perturbed in IBD patients. In recent years, metabolomics studies have revealed a consistent defect in bile acid metabolism with an increase in primary bile acids and a reduction in secondary bile acids in IBD patients. This review explores the evolving evidence that specific bile acid metabolites interact with intestinal epithelial and immune cells to contribute to the inflammatory milieu seen in IBD. Furthermore, we summarise evidence linking bile acids with intracellular pathways that are known to be relevant in IBD including autophagy, apoptosis, and the inflammasome pathway. Finally, we discuss how novel experimental and bioinformatics approaches could further advance our understanding of the role of bile acids and inform novel therapeutic strategies in IBD.
Highlights
Inflammatory Bowel Disease (IBD), comprising Ulcerative Colitis (UC) and Crohn’s disease (CD), is a complex immune-mediated inflammatory disorder of the gastrointestinal tract
Whilst metagenomic approaches have characterised the dysbiosis occurring in Inflammatory bowel disease (IBD) patients (e.g. an increase in Proteobacteria and a decrease in Firmicutes species [4]) they have failed to demonstrate whether dysbiosis is a cause or effect of inflammation, and how this might disrupt the host-microbiota mutualistic relationship [5]
Emerging evidence indicates that the shift in Primary bile acids (PBAs) and secondary bile acids (SBAs) composition detected in IBD patients may contribute to proinflammatory intestinal mucosal responses through differential effects on epithelial and immune cells compared to the normal state
Summary
Inflammatory Bowel Disease (IBD), comprising Ulcerative Colitis (UC) and Crohn’s disease (CD), is a complex immune-mediated inflammatory disorder of the gastrointestinal tract. A variety of experimental approaches have revealed that perturbations to the gut microbiome resulting in loss of gut microbial species containing BSH and 7a-dehydroxylation enzymes, and subsequent increases in conjugated PBAs (in particular taurocholic acid) and reductions in SBAs, promote Clostridium difficile spore germination and growth in the gut [37,38,39]. These studies have been helpful in gaining initial insights into the changes occurring in the gut BA composition of IBD patients, further work is required to address important unanswered questions in particular, characterising the functional consequences this may have on the regulation of intestinal inflammatory responses.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
