Gut-prostate axis in prostate cancer: microbiome signatures, mechanistic insights, and therapeutic opportunities

Prostate cancer (PCa) is one of the most common malignant tumors in men, and its onset and progression may be closely associated with an imbalance in the gut microbiota. Existing studies indicate that PCa patients exhibit reduced fecal microbiota diversity and altered microbiota composition, with the abundance of certain bacterial genera correlated with disease risk and progression. Mechanistically, the gut microbiota may regulate signaling pathways such as IGF-1, MAPK/PI3K, and NF-κB through metabolites including short-chain fatty acids, bile acids, and microbiota-derived androgens, thereby potentially contributing to tumor proliferation, inflammatory responses, and immune evasion. Androgen deprivation therapy (ADT) can also reshape the gut microbiota; certain bacterial populations may contribute to the development of castration resistance through androgen metabolism, while changes in bacteria such as Akkermansia muciniphila are associated with treatment response. Currently, strategies such as dietary interventions, probiotics, and fecal microbiota transplantation have shown some promise; however, most existing studies are small-sample or cross-sectional in nature, and causal relationships remain unclear. Future studies should combine multicenter longitudinal cohorts with multi-omics technologies to further elucidate the translational value of the gut microbiota in PCa screening, risk stratification, prognostic assessment, treatment-response prediction, toxicity monitoring, and personalized microbiome-targeted interventions.