Dual Role of Microbial Short-Chain Fatty Acids in Colorectal Cancer Development and Prevention

The human gut microbiota forms an intricate ecosystem, pivotal for host health, primarily through the production of microbial metabolites known as short-chain fatty acids (SCFAs). These SCFAs, chiefly acetate, propionate, and butyrate, are generated from the fermentation of dietary fibers in the colon and exert profound influences on colorectal cancer (CRC) development and prevention. SCFAs play a critical, yet paradoxical, role in CRC, demonstrating both tumor-suppressive and, under specific conditions, tumor-promoting effects. Key mechanisms involved include the activation of G-protein coupled receptors (GPCRs) and the inhibition of histone deacetylases (HDACs), which collectively modulate immune responses, maintain intestinal barrier integrity, and influence cellular metabolism. Understanding these complex interactions is essential for harnessing SCFAs in clinical and therapeutic applications, aiming to improve patient outcomes through targeted interventions and precision nutrition strategies.