FIGURE 2.

Biosynthesis and enterohepatic circulation of bile acids showing the individual transport proteins expressed in hepatocytes and enterocytes. Primary bile acids synthesized in the liver from cholesterol are cholic acid (CA) and chenodeoxycholic acid (CDCA). The primary bile acids are then conjugated with glycine or taurine in the liver and released into the gallbladder. Gut microbiota present in the intestine, by deconjugation, dehydroxylation, dehydrogenation and epimerization, modify the primary bile acids converting them to the secondary bile acids-deoxycholic acid (DCA), lithocholic acid (LCA), and ursodeoxycholic acid (UDCA). Around 95% of bile acids are reabsorbed into the distal ileum. Transporters involved in enterohepatic circulation of bile acids are apical sodium-dependent bile transporter (ASBT) present in the brush border membrane of the enterocyte, ileal bile acid-binding protein (IBABP) involved in trans-enterocyte shuttle of bile acid, basolateral organic solute transporters, OSTα/OSTβ that facilitate efflux into the portal circulation. Bile acids are actively transported into hepatocytes by sodium sodium-taurocholate cotransporting polypeptide (NTCP) and organic anion transporters (OATP) while bile salt export pump (BSEP) and multidrug resistance-associated protein-2 (MRP2) are involved in the process of exporting bile acids out of hepatocytes. Bile acids activation of FXR signaling pathways regulates the expression of these transporters. In the hepatocyte, bile acid activation of FXR increases SHP expression, decreases the expression of NTCP and OATP, while increases the expression of MRP2 and BSEP. In ileal enterocytes, bile acids signaling leads to upregulation of IBABP and OSTα/OSTβ and downregulation of ASBT. (Bile acid direction is presented by black dashed narrow.)