Polysaccharides Alleviate Cancer Through the Action of Gut Microbiota

This paper systematically explores the mechanisms and clinical translation potential of polysaccharides in cancer suppression through modulation of the gut microbiota. As natural bioactive macromolecules, polysaccharides directly inhibit tumor cell proliferation via unique physicochemical interactions and indirectly regulate the tumor microenvironment and host immunity by restoring gut microbial homeostasis. Evidence indicates that polysaccharides selectively enrich short-chain fatty acid (SCFA)-producing bacteria (e.g., Bifidobacterium and Akkermansia) while suppressing pro-inflammatory pathogens, thereby reducing chronic inflammation, enhancing immune surveillance, and increasing sensitivity to chemotherapeutic drugs. Moreover, polysaccharide metabolites such as butyrate exert dual anticancer effects through epigenetic regulation (e.g., inhibition of histone deacetylases) and metabolic reprogramming of cytotoxic immune cells (e.g., enhanced mitochondrial function in CD8 T cells). This paper also proposes precision medicine strategies based on the polysaccharidemicrobiota axis, including engineered polysaccharidemicrobe conjugates for spatiotemporal control of metabolite production and synergistic combinations of polysaccharides with chemotherapy or immunotherapy (e.g., enhancing oxaliplatin efficacy by 41% while mitigating gut dysbiosis). These findings provide a foundation for next-generation personalized cancer therapies and highlight the unique advantages of polysaccharides in minimally invasive, low-toxicity oncological treatments.