Emerging Mechanisms Linking High-Fat Diet and Endometrial Cancer: Insights into the Role of Gut Microbiota and Metabolic Dysregulation

Abstract

High-fat diet (HFD) consumption has been recognized as a significant risk factor for the development of endometrial carcinoma (EC). Emerging research highlights gut microbiota as crucial mediators of HFD-induced systemic effects, which not only promote metabolic disorders such as obesity, insulin resistance, and systemic inflammation but also lead to profound alterations in gut microbiota composition. These changes subsequently influence estrogen metabolism, inflammatory signaling pathways, and endometrial remodeling, thereby exacerbating cellular proliferation and atypical changes within the endometrium. The underlying mechanisms may involve dysbiotic shifts in intestinal flora that contribute to increased endotoxemia, compromised intestinal barrier function, and chronic low-grade inflammation. This review synthesizes current findings on how HFD-induced gut microbiota dysbiosis and metabolic dysregulation contribute to the pathogenesis of EC while highlighting potential preventive and therapeutic strategies.