The Emerging Role of Bile Acids in the Pathogenesis of Inflammatory Bowel Disease

Frontiers in Immunology

Immunology

Nick Powell¹  Simon M. Rushbrook²  Dezso Modos³  John P. Thomas⁴  Tamas Korcsmaros⁵ 

[1] Division of Digestive Diseases, Imperial College London, London, United Kingdom;Gut Microbes and Health Programme, Quadram Bioscience, Norwich, United Kingdom;Department of Gastroenterology, Norfolk and Norwich University Hospital, Norwich, United Kingdom;Department of Hepatology, University of East Anglia Medical School, Norwich, United Kingdom;Gut Microbes and Health Programme, Quadram Bioscience, Norwich, United Kingdom;Organisms and Ecosystem, Earlham Institute, Norwich, United Kingdom;Gut Microbes and Health Programme, Quadram Bioscience, Norwich, United Kingdom;Organisms and Ecosystem, Earlham Institute, Norwich, United Kingdom;Department of Gastroenterology, Norfolk and Norwich University Hospital, Norwich, United Kingdom;Gut Microbes and Health Programme, Quadram Bioscience, Norwich, United Kingdom;Organisms and Ecosystem, Earlham Institute, Norwich, United Kingdom;Division of Digestive Diseases, Imperial College London, London, United Kingdom;

关键词: bile acids;    immunology and inflammation;    gut metabolites;    inflammatory bowel disease;    Crohn’s disease;    ulcerative colitis;    gut microbiome;   

DOI  :  10.3389/fimmu.2022.829525

 received in 2021-12-05, accepted in 2022-01-14,  发布年份 2022

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

Unknown   
Copyright © 2022 Thomas, Modos, Rushbrook, Powell and Korcsmaros