Gallstones in the Era of Metabolic Syndrome: Pathophysiology, Risk Prediction, and Management

Gallstone disease (GSD) and metabolic syndrome (MetS) are increasingly prevalent conditions with significant global health implications. Recent evidence highlights a strong epidemiological association between these disorders, driven by shared pathophysiological mechanisms. This review provides a comprehensive analysis of the intricate relationship between MetS and GSD, focusing on the role of insulin resistance, dyslipidemia, obesity, and gut microbiota dysbiosis in gallstone formation. An integrated pathophysiological model is proposed, linking metabolic disturbances to bile cholesterol supersaturation, gallbladder dysmotility, and chronic inflammation. The review also explores clinical implications, including risk prediction models based on metabolic parameters, early detection biomarkers, and targeted interventions such as lifestyle modifications, pharmacological therapies, and microbiome modulation. By addressing the metabolic underpinnings of GSD, this synthesis offers a foundation for developing preventive and therapeutic strategies to mitigate the burden of these interconnected conditions. Future research directions are outlined to refine mechanistic insights and improve clinical outcomes.