Gut microbiota-derived short-chain fatty acids in gallstones: mechanisms and intervention strategies

Gallstones are a common digestive disease in humans. They may result in cholecystitis, cholangitis, and other complications, thereby causing serious harm to human health. Accumulating evidence suggests that gut dysbiosis is associated with gallstone formation. As key metabolites of the gut microbiota, short-chain fatty acids (SCFAs) may exert protective effects on gallstones through multiple mechanisms. These mechanisms include regulating lipid and bile acid metabolism, maintaining the intestinal barrier, modulating the microbial community structure, and reducing the risk of cholecystitis. However, a systematic synthesis of these mechanisms is still lacking. Therefore, this review provides a comprehensive overview of the research progress on this topic. It systematically mapped the metabolic pathways of core SCFA-producing bacteria and consolidated the current evidence for their potential anti-lithogenic effects. We also analyzed possible mechanisms by which SCFAs might suppress gallstone formation. Furthermore, clinical intervention strategies are proposed and critical knowledge gaps are identified. A deeper insight into the link between SCFAs, their producers, and gallstones may reveal novel preventive and therapeutic targets.