Metabolic Regulation of the Intestinal Mucosal Interface in Obesity-Associated Colorectal Carcinogenesis: Mechanisms, Biomarkers, and Therapeutic Opportunities

The global rise in obesity has paralleled an increasing incidence of colorectal cancer (CRC), particularly early-onset CRC, highlighting the need to better understand the mechanisms linking metabolic dysfunction to colorectal carcinogenesis. While chronic inflammation and gut microbial dysbiosis are recognized contributors, the biological processes integrating systemic metabolic alterations with local intestinal pathology remain incompletely understood. In this review, we propose the intestinal mucosal interface as the central biological platform through which obesity promotes CRC development. We describe how obesity-associated alterations in adipokine secretion, insulin/insulin-like growth factor-1 (IGF-1) signaling, bile acid metabolism, and chronic inflammation disrupt epithelial barrier integrity, goblet-cell function, intestinal stem-cell regulation, mucosal immunity, and host–microbiota interactions. Collectively, these changes create a metabolically altered microenvironment that favors epithelial transformation and early colorectal carcinogenesis. We also discuss emerging biomarkers that reflect metabolic, epithelial, microbial, and immune dysfunction, together with therapeutic strategies aimed at restoring intestinal homeostasis through metabolic intervention, microbiota modulation, and immune-targeted approaches. This integrated framework extends the traditional barrier–microbiota–inflammation model and identifies the intestinal mucosal interface as a promising target for risk stratification, early detection, prevention, and precision therapy in obesity-driven CRC.