Bile acids and their receptors: Potential therapeutic targets in inflammatory bowel disease

Figure 1 Synthesis, recirculation, and microbial modification of bile acids in the gut. Bile acids are synthesized from cholesterol in the liver. In the classical pathway, cholesterol-7α-hydroxylase converts cholesterol to 7α-hydroxycholesterol, which is then metabolized to cholic acid via mitochondrial sterol-27-hydroxylase (CYP27A1) or CYP8A1, or to chenodeoxycholic acid (CDCA) via CYP27A1. In the alternative pathway, CYP27A1 begins the conversion of cholesterol to 27-hydroxycholesterol, which is then metabolized to CDCA by oxysterol 7α-hydroxylase. These primary bile acids are then conjugated with taurine or glycine and then released into the bile for secretion into the duodenum. At the end of the ileum, 95% of the conjugated bile acids (BAs) are reabsorbed through the enterohepatic circulation, while the remaining 5% depolymerizes and enters the colon, where BAs undergo a series of chemical modifications by intestinal bacteria, including catabolism, desulfurization, dehydrogenation, dehydroxylation, and exo-embedding reactions to form secondary bile acids (mainly lithocholic acid and deoxycholic acid) and their oxidative, isomeric, and exo-derivatives. IBD: Inflammatory bowel disease; CA: Cholic acid; CDCA: Chenodeoxycholic acid; GCA: Glycocholic acid; TCA: Taurocholic acid; GCDCA: Glycochenodeoxycholic acid; TCDCA: Taurochenodeoxycholic acid; DCA: Deoxycholic acid; LCA: Lithocholic acid; BA: Bile acid; CYP7A1: Cholesterol-7α-hydroxylase; CYP27A1: Mitochondrial sterol-27-hydroxylase; CYP8B1: Sterol-12α-hydroxylase; CYP7B1: Oxysterol 7α-hydroxylase; BSHs: Bile salt hydrolases; FXR: Farnesol X receptor; FGF: Fibroblast growth factor; SHP: Small isomeric partner.