Abstract:Cholecystectomy is a widely used surgical treatment for benign gallbladder diseases, and its potential long-term health consequences have attracted increasing attention. Epidemiological studies have suggested that cholecystectomy may be associated with increased risks of colorectal cancer, cardiovascular disease, metabolic dysfunction-associated steatotic liver disease, cirrhosis, and hepatocellular carcinoma; however, a causal relationship between cholecystectomy and these long-term outcomes has not been established. In this review, we use the bile acid-gut microbiota-inflammation axis as a framework to summarize the interplay among altered bile acid metabolism, gut microbiota dysbiosis, and chronic low-grade inflammation after cholecystectomy, and further discuss their potential roles in the development of colorectal cancer, atherosclerosis, metabolic dysfunction-associated steatotic liver disease, cirrhosis, and hepatocellular carcinoma. Large population-based cohort studies and meta-analyses are integrated with mechanistic evidence to evaluate the consistency and limitations of current findings, with particular emphasis on reverse causation, residual confounding, and indication bias that may complicate causal inference. Potential interventions targeting bile acid signaling, gut microbiota, and metabolic abnormalities are also summarized, and future research priorities are proposed, including identification of high-risk populations, personalized microbiota-based interventions, and multi-omics validation of underlying mechanisms. Current evidence suggests that cholecystectomy may contribute to the development of multiple long-term diseases through disruption of the bile acid-gut microbiota-inflammation axis, but its independent effects and underlying mechanisms remain to be clarified. In clinical practice, the potential long-term metabolic and microbiota-related consequences should be considered alongside the established benefits of cholecystectomy, and appropriate long-term follow-up should be encouraged.