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

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.

Predicting metabolomic profiles from microbial composition through neural ordinary differential equations

“…Here we focused on the dataset PRISM + NLIBD because gut microbiomes of human adults have been investigated more extensively. For this purpose, we focused on the bile acid metabolism which is relatively well-studied [50, 51, 52, 53, 54] and is shown to be associated with human gastrointestinal diseases such as gastrointestinal cancers [53] and IBD [55, 56]. We carefully chose metabolites that are related to the primary, conjugated, and secondary forms of cholate and chenodeoxycholate.…”

Bile acids induce Ca2+ signaling and membrane permeabilizations in vagal nodose ganglion neurons

“…In summary, we demonstrated that two BAs DCA and TCA induce different Ca 2+ signals and have distinct properties for BA-induced cell permeabilization. Our results suggest that at lower concentrations DCA may act as a signaling molecule on vagal NG neurons, however, at higher concentrations, it can lead to cell death, which may contribute to pathological changes in several inflammatory bowel diseases [ 41 ].…”

Alterations and Potential Applications of Gut Microbiota in Biological Therapy for Inflammatory Bowel Diseases

“…Furthermore, these characteristic alterations of BAs are considered to correlate with the disease severity of IBD ( Duboc et al, 2013 ; Kriaa et al, 2022 ). Recent studies have also provided evidence for the involvement of BAs in IBD-associated autophagy, apoptosis, and inflammasome pathways ( Thomas et al, 2022 ). Meanwhile, the interactions of BAs with intestinal epithelial cells and immune cells have also been revealed, further providing novel insights into the gut microbiota-BA-host axis in the pathogenesis of IBD ( Yang et al, 2021 ; Kriaa et al, 2022 ).…”