Gut Microbiota-Derived Natural Metabolites in Obesity-Associated Colorectal Cancer: A Therapeutic Perspective

The rising global prevalence of obesity has significantly increased the burden of colorectal cancer (CRC), now recognized as one of the leading causes of cancer-related morbidity and mortality worldwide. Recent advances in microbiome research have highlighted the intricate interplay between obesity, gut microbiota, and colorectal carcinogenesis. Obesity-induced dysbiosis not only perturbs intestinal homeostasis but also alters the production of gut microbiota-derived natural metabolites, many of which possess critical bioactive properties. These microbial metabolites such as short-chain fatty acids (SCFAs), secondary bile acids, indole derivatives, and polyphenol catabolites, play pivotal roles in modulating host immunity, inflammation, cell proliferation, and apoptosis. While certain metabolites may exacerbate tumorigenesis, others demonstrate protective or chemopreventive effects, thereby representing a novel frontier for therapeutic exploration. This review provides an integrated overview of how obesity reshapes gut microbial ecology and the metabolic landscape, examines the roles of specific microbial-derived metabolites in colorectal cancer development, and evaluates current and emerging therapeutic strategies that harness these metabolites for cancer prevention and treatment. Understanding the mechanistic underpinnings of these host-microbe interactions offers promising opportunities for precision medicine, including microbiota-targeted dietary interventions, probiotic formulations, and metabolite-based drug development to mitigate the dual burden of obesity and colorectal cancer.