Gallstone is a prevalent metabolic disorder worldwide. Its pathogenesis involves multiple factors such as bile component imbalance, cholesterol metabolic dysregulation, and a chronic inflammatory microenvironment. Recent studies revealed that dysbiosis of the gut and gallbladder microbiota drives gallstone formation through a "metabolic-immuno-inflammatory" triple mechanism: microbiota alters the bile acid metabolism, activates immune pathways (e.g., NF-κB), and generate pro-lithogenic metabolites (e.g., trimethylamine N-oxide). This review summarizes the microbial features of patients with gallstone disease, the functions of microbiota-derived metabolites, and the role of the gut-bladder axis in cholesterol homeostasis disruption. Furthermore, it discusses novel preventive and therapeutic strategies targeting the microbiota (e.g., probiotics, modulation of the farnesoid X receptor) and the development of multi-omics biomarkers.

Gallstone is a prevalent metabolic disorder worldwide. Its pathogenesis involves multiple factors such as bile component imbalance, cholesterol metabolic dysregulation, and a chronic inflammatory microenvironment. Recent studies revealed that dysbiosis of the gut and gallbladder microbiota drives gallstone formation through a "metabolic-immuno-inflammatory" triple mechanism: microbiota alters the bile acid metabolism, activates immune pathways (e.g., NF-κB), and generate pro-lithogenic metabolites (e.g., trimethylamine N-oxide). This review summarizes the microbial features of patients with gallstone disease, the functions of microbiota-derived metabolites, and the role of the gut-bladder axis in cholesterol homeostasis disruption. Furthermore, it discusses novel preventive and therapeutic strategies targeting the microbiota (e.g., probiotics, modulation of the farnesoid X receptor) and the development of multi-omics biomarkers.