Gut Microbiome Dysbiosis at the Intersection of Obesity, Diabetes, and Colorectal Cancer

The gut microbiome plays a pivotal role in maintaining host metabolic homeostasis, immune function, and intestinal integrity. Dysbiosis being an imbalance in the microbial ecosystem, has been implicated in the pathogenesis of metabolic diseases such as obesity and type 2 diabetes mellitus (T2DM), as well as colorectal cancer (CRC). Emerging evidence reveals intricate crosstalk among these conditions, suggesting that microbiome alterations act as a shared mechanistic link. In obesity and T2DM, gut microbial changes promote chronic inflammation, insulin resistance, and metabolic endotoxemia through increased production of lipopolysaccharide (LPS) and decreased short-chain fatty acids (SCFAs). These same alterations influence colorectal carcinogenesis by disrupting epithelial barrier function, modulating oncogenic signaling, and altering bile acid metabolism. Moreover, gut microbial-derived metabolites can affect epigenetic regulation and immune responses, fostering a tumor-promoting microenvironment. Understanding these interrelationships offers novel insights into disease pathophysiology and highlights the therapeutic potential of microbiota-targeted interventions, including probiotics, prebiotics, dietary modulation, and fecal microbiota transplantation (FMT). This review explores the current evidence linking gut microbiome dysbiosis to the obesity-diabetes-CRC axis and discusses future directions for research and therapy.