The gut microbiota in colorectal cancer: role in cytokine regulation, intestinal immune barrier dysfunction.

Colorectal cancer (CRC) remains a leading cause of cancer-related morbidity and mortality worldwide. In addition to genetic susceptibility and environmental exposures, accumulating evidence suggests that the gut microbiota plays a critical role in colorectal carcinogenesis. Dysbiosis of the intestinal microbiota can reshape both local and systemic immune landscapes through persistent inflammatory signaling, aberrant cytokine production, and disruption of the intestinal immune barrier. These microbiota-driven alterations contribute to epithelial injury, chronic inflammation, tumor initiation, and disease progression. Recent advances have highlighted complex interactions among gut microorganisms, cytokine networks, and immune cells within the tumor microenvironment, as well as their influence on responses to anticancer therapies. Microbial metabolites and pathogen-associated molecular patterns can activate key signaling pathways, including nuclear factor-κB and signal transducer and activator of transcription 3, thereby modulating immune surveillance and tumor-promoting inflammation. However, most current evidence is derived from preclinical models, and the causal relationships between specific microbial signatures and CRC remain to be fully established. In this review, we provide a comprehensive and critical overview of current evidence on the role of the gut microbiota in CRC, with a particular focus on microbiota-mediated regulation of cytokines and the intestinal immune barrier. We further discuss the mechanistic links between dysbiosis, immune dysregulation, and colorectal tumorigenesis, and highlight emerging therapeutic strategies targeting the microbiota-immune axis. A better understanding of these interactions may facilitate the development of microbiota-based diagnostic and therapeutic approaches for CRC.