Figure 3.

Interplay of bile acids with transporters, metabolizing enzymes, and the microbiome in the liver, intestine, and kidney. (a) In hepatocytes, bile acids control their own biosynthesis through negative feedback on CYP7A1 and CYP27A1. Cholesterol‐derived bile acids are negatively charged at physiologic pH and require carrier‐mediated transport to cross membranes. Blood to bile transport is governed by Na + taurocholate cotransporting peptide (NTCP), OATP1A2, OATP1B1, and OATP1B3. Secretion of bile acids from the liver into the bile canaliculi occurs primarily by BSEP and MRP2 to a lesser extent. MRP3, MPR4, and OSTα‐OSTβ play a compensatory role in bile acid efflux under cholestatic conditions. (b) Following the delivery of bile acids to the intestinal lumen through the bile ducts, bile acids are actively transported across the apical intestinal brush border membrane by ASBT, followed by efflux across the basolateral membrane and into the portal circulation by OSTα‐OSTβ. Additionally, bile acids in the gut lumen interact with intestinal microbes. Bile acids have direct antimicrobial effects on gut microbes. Conversely, deconjugation of bile acids by gut microbes prevents ASBT‐directed intestinal reuptake. (c) Bile acids are reclaimed in the kidney by active reabsorption in the proximal tubules. The transport mechanisms involved in renal tubular reabsorption involve ASBT and OSTα‐OSTβ expressed on the apical and basolateral membranes, respectively, while OAT3 contributes to secretion. Throughout these pathways, bile acids act as signaling molecules as ligands for G protein–coupled receptors and nuclear receptors. [Colour figure can be viewed at wileyonlinelibrary.com]