The Interplay Between Obesity, Gut Microbiota and Early-onset Colorectal Cancer

The global incidence of colorectal cancer (CRC) is rising at an alarming rate, particularly among individuals under the age of 50, referred to as early-onset CRC (EOCRC). While genetic predisposition accounts for approximately 20% of the total cases, the majority are influenced by environmental and lifestyle factors. Among these, the rising prevalence of obesity is a major modifiable contributor to EOCRC pathogenesis. This narrative review explores the multifaceted role of obesity in EOCRC, focusing on how diet-induced adiposity reshapes the gut microbiota and host metabolic signaling. We synthesize evidence on how obesity-associated dysbiosis, characterized by the depletion of protective, short-chain fatty acid (SCFA)-producing bacteria and the enrichment of genotoxic pathobionts, compromises intestinal barrier integrity and promotes a “leaky gut” phenotype. In addition, we explore the systemic consequences of obesity-driven inflammation, including M1-polarized macrophage infiltration into adipose tissue, dysregulated adipokine signaling, and the hyperactivation of the insulin-IGF-1 axis. By integrating epidemiological data with molecular mechanisms, this review highlights how the synergy between metabolic dysfunction and microbial alterations creates a fertile niche for early-onset carcinogenesis. These findings underscore the importance of targeting lifestyle interventions to mitigate the rising burden of obesity and reduce the risk of EOCRC progression.