Gut microbiome-derived metabolites in prostate cancer: microbial mechanisms of immune modulation, androgen metabolism, and therapeutic implications

The global burden of prostate cancer continues to rise, yet conventional biomarkers and therapies face substantial limitations due to tumor heterogeneity and treatment resistance. The gut microbiome has emerged as a critical regulator of host metabolism and immunity, with its bioactive metabolites influencing prostate cancer pathogenesis through multiple interconnected pathways. Short-chain fatty acids, secondary bile acids, microbiota-modulated tryptophan metabolites, and microbiota-derived androgens modulate immune surveillance, androgen metabolism, and therapeutic responses via hormonal and inflammatory signaling networks. These metabolites exert context-dependent effects that vary with concentration, disease stage, and the tumor microenvironment. This narrative review comprehensively synthesizes current mechanistic evidence on microbiome-derived metabolite signaling and evaluates the potential of circulating microbial metabolites as non-invasive biomarkers, while outlining future research priorities for clinical translation in prostate cancer management.