How obesity, gut microbes, and cannabinoid biology may shape cancer

Colorectal cancer (CRC) is a multifactorial disease strongly influenced by genetic and environmental factors, as well as by immune and metabolic disorders such as obesity and gut dysbiosis. Recent evidence highlights the interplay between the endocannabinoidome (eCBome) and the gut microbiota as a central regulatory axis of intestinal homeostasis, metabolism, and immune responses. Although no studies have directly investigated this functional interaction in the CRC context, recent evidence suggests that dysfunction of the eCBome-microbiota axis, commonly observed in obesity, may influence colorectal tumorigenesis by impairing intestinal barrier integrity, increasing endotoxemia and immune dysregulation, altering microbial metabolite production, and activating NF-κB-mediated pro-tumorigenic signaling pathway. This is the first review to comprehensively integrate current evidence linking obesity-associated eCBome-microbiota dysfunction with CRC-related mechanisms and to propose potential pathways through which this interaction may influence CRC pathogenesis, providing a framework to guide future studies and support the development of novel preventive and therapeutic strategies for CRC.