The emerging role of bile acids in the pathogenesis of inflammatory bowel disease
File(s)
Author(s)
Thomas, John P
Modos, Dezso
Rushbrook, Simon M
Powell, Nick
Korcsmaros, Tamas
Type
Journal Article
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.
Date Issued
2022-02-03
Date Acceptance
2022-01-14
Citation
Frontiers in Immunology, 2022, 13
ISSN
1664-3224
Publisher
Frontiers Media
Journal / Book Title
Frontiers in Immunology
Volume
13
Copyright Statement
© 2022 Thomas, Modos, Rushbrook, Powell and Korcsmaros. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
License URL
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000759917000001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Life Sciences & Biomedicine
Immunology
bile acids
immunology and inflammation
gut metabolites
inflammatory bowel disease
Crohn's disease
ulcerative colitis
gut microbiome
FECAL MICROBIOTA TRANSPLANTATION
ACTIVE ULCERATIVE-COLITIS
URSODEOXYCHOLIC ACID
GUT MICROBIOTA
DEOXYCHOLIC-ACID
EPITHELIAL-CELLS
INTESTINAL INFLAMMATION
CHEMOPREVENTIVE AGENT
INFLIXIMAB THERAPY
TUMOR PROMOTER
Publication Status
Published
Article Number
ARTN 829525