Bile Acids: Key Players in Inflammatory Bowel Diseases?

Abstract

Inflammatory bowel diseases (IBDs) have emerged as a public health problem worldwide with a limited number of efficient therapeutic options despite advances in medical therapy. Although changes in the gut microbiota composition are recognized as key drivers of dysregulated intestinal immunity, alterations in bile acids (BAs) have been shown to influence gut homeostasis and contribute to the pathogenesis of the disease. In this review, we explore the interactions involving BAs and gut microbiota in IBDs, and discuss how the gut microbiota-BA-host axis may influence digestive inflammation.

Keywords: bile acids; gut microbiota; holobiont; inflammatory bowel diseases; microbiome.

Figure 1

Bile acid synthesis. In the liver, bile acid metabolism mainly produces two primary bile acids, cholic acid and chenodeoxycholic acid. In the intestine, primary bile acids serve as substrates for microbial metabolism by the gut microbiota to generate secondary bile acids, including deoxycholic acid, lithocholic acid and ursodeoxycholic acid.

Figure 2

BA profiles in healthy large intestine and IBDs. Under physiological conditions, BAs are metabolized by the gut microbiota through bile salt hydrolase deconjugation and 7α-dehydroxylation into secondary BAs such as DCA and LCA. Abnormal BA biosynthesis and metabolic processes were reported in IBDs with increased primary BA levels, which in turn altered the composition of the gut microbiota and were associated with a lower production of deconjugated and secondary BAs. IBDs: inflammatory bowel diseases; BAs: bile acids; CA: cholic acid; CDCA: chenodeoxycholic acid; T/GCA: taurine/glycine-conjugated cholic acid; T/GCDCA: taurine/glycine-conjugated chenodeoxycholic acid; DCA: deoxycholic acid; LCA: lithocholic acid; BSH: bile salt hydrolase.