Transporter-mediated interorgan crosstalk in bile acid metabolic diseases

Bile acids not only participate in lipid digestion and absorption but also act as multi-functional signaling molecules to regulate physiological processes such as glycolipid metabolism, immune homeostasis, and energy metabolism, which mediate metabolic dialogue among multiple organs, including the liver, intestine, kidney, and brain. Disrupted bile acid metabolism promotes the progression of multiple diseases, including cholestatic liver disease, metabolic dysfunction-associated steatotic liver disease, hepatic encephalopathy, cholemic nephropathy, and bile acid-related diarrhea. A series of bile acid transporters is arranged along the gut-liver-kidney-brain axis. They precisely regulate the bile acid metabolic homeostasis of the body by governing their uptake and efflux. Abnormal expressions and function of these transporters dominate the outcome of cholestasis, leading to crosstalk in bile acid metabolic diseases. This review systematically introduces bile acid transporters, elucidates the interorgan interaction mechanism mediated by their functional disorders in bile acid metabolic diseases, and emphasizes the direct or indirect targeted regulation of bile acid metabolism by transporters and the precise intervention strategies for related diseases. It provides a theoretical basis and new ideas for the diagnosis and treatment of bile acid metabolic diseases.