The antitumor mechanism of polysaccharides through regulating the microbiota-metabolism-immune axis and their clinical application strategies.
In recent years, the interaction between gut microbiota and dietary polysaccharides has emerged as a research hotspot, particularly regarding their antitumor potential. Accumulating evidence underscores the gut microenvironment as a pivotal player in tumorigenesis and cancer progression. Natural polysaccharides, known for their prebiotic effects and antitumor activities, represent promising candidates for developing safe and effective antitumor therapeutics. This review focuses on polysaccharides that are selectively utilized by gut microbiota, exploring their structure-activity relationship (SAR) and the mechanisms underlying their antitumor effects via the microbiota-metabolite-immunity axis. We systematically elucidate how these polysaccharides enrich beneficial bacteria, suppress pathogens, and facilitate the production of microbial metabolites that reshape the tumor immune microenvironment and inhibit cancer initiation, metastasis, and progression. Additionally, we summarize recent advances in clinical applications of polysaccharides, offering new perspectives for microbiota-targeted multi-modal strategies in cancer prevention and treatment.