Figure 1.

Enterohepatic circulation and modification of bile acids in the intestine by the gut microbiome. In the liver, cholesterol is converted to cholic acid (CA) and chenodeoxycholic acid (CDCA) (de novo synthesis). CA and CDCA are then conjugated with glycine or taurine (G/T). Conjugated CA and CDCA are transferred to and stored in the gallbladder; food intake stimulates their release into the intestine. Conjugated BAs are deconjugated by bile salt hydrolases (BSHs) of gut bacteria in the gut microbiome. By bile acid-inducible (bai) operon genes of gut bacteria, CA and CDCA are then dehydrogenated and converted to deoxycholic acid (DCA) and lithocholic acid (LCA), respectively. CDCA is also converted to ursodeoxycholic acid (UDCA) by dehydrogenation and epimerization by hydroxysteroid dehydrogenases (HSDHs) of gut bacteria. Approximately 95% of BAs in the intestine are reabsorbed and transported to the liver, and the remainder is excreted in the feces. This circulation between the gut and the liver is termed enterohepatic circulation. Some of the BAs reabsorbed from the intestine spill into the systemic circulation. Unconjugated BAs from the gut are conjugated with G/T in the liver. Blue boxes represent primary BAs. Green boxes represent secondary BAs. Pink boxes represent glycine or taurine (G/T).