Bile acid signaling: from dynamic pool composition to inter-organ communication

Bile acids (BAs) are synthesized in the liver and extensively modified by gut microbiota in the intestine. The dynamic composition of the BA pool enables BAs to modulate metabolic responses at varying degrees. By activating nuclear (e.g., FXR) and membrane (e.g., TGR5) receptors, BAs integrate metabolic and immune processes across the enterohepatic circulation and peripheral tissues, forming a systemic homeostatic network. Dysregulation of this network is causally linked to metabolic dysfunction-associated steatotic liver disease (MASLD), type 2 diabetes mellitus, and other disorders. Targeting BA signaling has shown therapeutic potential in preclinical studies, though clinical translation requires further exploration. This review elucidates the dynamic composition of the BA pool, the integrated regulatory roles of BA signaling networks in health and disease, and highlights emerging therapeutic strategies that target the BA signaling-including FXR agonists, TGR5 modulators, and microbiota-derived BA interventions-for metabolic and immune-mediated diseases.