Host bile acid signaling pathways

Host bile acid signaling pathways represent a complex physiological network that coordinates systemic metabolism and immune responses through the action of bile acids as signaling molecules. These pathways are primarily mediated by a set of host receptors, most notably the nuclear farnesoid X receptor (FXR) and the membrane-bound G protein-coupled bile acid receptor 1 (TGR5/GPBAR1), along with others such as the vitamin D receptor (VDR) and pregnane X receptor (PXR) [1, 3, 4]. Bile acids act as ligands for these receptors, triggering transcriptional and signaling cascades that regulate bile acid synthesis, lipid and glucose homeostasis, and energy expenditure [6, 8]. Dysregulation of these pathways is implicated in a wide range of conditions, including cholestatic liver diseases like primary biliary cholangitis (PBC), metabolic-associated steatotic liver disease (MASLD), and type 2 diabetes [2, 12]. Pharmacological interventions targeting this system, such as FXR agonists (e.g., obeticholic acid) and apical sodium-dependent bile acid transporter (ASBT) inhibitors, aim to restore metabolic balance and reduce hepatic inflammation and fibrosis [1, 14]. These therapies leverage the endocrine functions of bile acids to treat chronic liver and metabolic disorders, though they are often associated with side effects like pruritus and lipid profile changes [1, 11].

Other names

Bile acid signalingBile acid receptor signalingEnterohepatic bile acid signalingMicrobiota-bile acid-host axis

Modulation of bile acid-activated receptors (e.g., FXR, TGR5) and transporters (e.g., ASBT) to regulate bile acid synthesis, secretion, and reabsorption, thereby influencing metabolic and inflammatory pathways.