Hydrophobic bile acids (BAs) (BAs)

Hydrophobic bile acids, such as deoxycholic acid (DCA) and lithocholic acid (LCA), are detergent-like molecules derived from cholesterol that serve as essential surfactants for lipid absorption and as potent signaling molecules (Perez & Briz, 2009, PMID: 19824010). While physiologically necessary, their accumulation—particularly in cholestatic liver diseases—leads to significant cytotoxicity, including mitochondrial dysfunction, oxidative stress, and apoptosis in hepatocytes and biliary epithelial cells (Beuers et al., 2015, PMID: 25618660). These molecules act as endogenous ligands for several receptors, most notably the Farnesoid X receptor (FXR) and the G protein-coupled bile acid receptor 1 (TGR5), which are critical regulators of bile acid synthesis, transport, and metabolic homeostasis (Makishima et al., 1999, PMID: 10339843; Maruyama et al., 2002, PMID: 12480923). Therapeutic strategies focus on reducing the toxic bile acid pool through sequestration in the gut using resins like cholestyramine, or by inhibiting their reabsorption via the apical sodium-dependent bile acid transporter (ASBT) with drugs like odevixibat (Al-Dury & Marschall, 2018, PMID: 29433771). Additionally, FXR agonists like obeticholic acid are used to suppress endogenous bile acid synthesis, while the administration of hydrophilic ursodeoxycholic acid (UDCA) helps to competitively displace more toxic hydrophobic species from the enterohepatic circulation.

Other names

Secondary bile acidsToxic bile saltsDeoxycholic acidLithocholic acidChenodeoxycholic acidBile acid pool

Bile acid sequestration, inhibition of apical sodium-dependent bile acid transporter (ASBT), activation of farnesoid X receptor (FXR) to suppress synthesis, and competitive displacement by hydrophilic bile acids.