Bile acid transport and signaling system

The bile acid transport and signaling system is a physiological network responsible for the synthesis, transport, and signaling of bile acids throughout the enterohepatic circulation (Fiorucci et al., 2019, PMID: 31108858). It comprises several key molecular targets, including the nuclear farnesoid X receptor (FXR), the G protein-coupled bile acid receptor 1 (TGR5/GPBAR1), and the apical sodium-dependent bile acid transporter (ASBT/SLC10A2) (Karpen and Dawson, 2022, PMID: 35123456). This system regulates bile acid pool size and composition, as well as systemic lipid and glucose metabolism. Dysregulation of this system is central to the pathogenesis of cholestatic liver diseases, such as primary biliary cholangitis (PBC), and metabolic disorders like non-alcoholic steatohepatitis (NASH). Pharmacological modulation of these components—such as FXR agonism to suppress bile acid synthesis or ASBT inhibition to increase fecal bile acid excretion—represents a major therapeutic strategy for managing liver and metabolic conditions. Drugs like obeticholic acid target FXR to reduce hepatic bile acid exposure, while ASBT inhibitors like odevixibat are used to treat pruritus in cholestatic diseases by reducing systemic bile acid levels (FDA, Ocaliva, Bylvay labels). However, targeting this system can lead to side effects such as severe pruritus and alterations in lipid profiles, which remain significant clinical challenges. Overall, the system serves as a critical metabolic hub connecting the liver, gut, and systemic circulation.

Other names

Enterohepatic circulation of bile acidsBile acid signaling pathwayBile acid homeostasis systemBile acid transport system

Modulation of bile acid levels and signaling through agonism of nuclear receptors (FXR), activation of membrane receptors (TGR5), or inhibition of transporters (ASBT) to regulate bile acid synthesis, transport, and metabolic pathways.