The microbiome across the prostate disease continuum: from health and BPH to prostatitis/CPPS and cancer

Microbial contributions to prostate health and disease extend beyond the mere detection of organisms in urine or tissue. Rather than acting as stable colonisers, microbial influences on the prostate are better conceptualised as converging fluxes: systemically circulating gut-derived metabolites, immune education occurring in distal lymphoid compartments, and intermittent exposure to microbial products from the lower urinary tract. These inputs converge on a limited set of conserved mediator-receptor axes-including short-chain fatty acids, bile acids and indole derivatives-that calibrate epithelial barrier integrity, inflammatory thresholds, antigen-presentation capacity and myeloid cell fate. Crucially, the biological relevance of these axes is stage-dependent. In benign prostatic hyperplasia and chronic prostatitis/chronic pelvic pain syndrome, metabolite tone shapes inflammatory activation thresholds and barrier resilience. In localized prostate cancer, these same pathways intersect with antigen-processing machinery and immune exclusion. In castration-resistant disease, tumour-intrinsic metabolic plasticity and redox balance predominate, with microbial and host-derived metabolites assuming relevance when they modulate lipid remodelling and ferroptotic vulnerability. Interpretation is constrained by the intrinsically low biomass of urine and prostate tissue. Robust inference therefore requires quantitative anchoring, orthogonal validation and explicit separation of association from causality. Translational progress is most likely to emerge from calibrated measurement and stage-aware modulation rather than indiscriminate ecological manipulation. By integrating mechanistic, spatial and clinical evidence, this Review proposes a stage-aware framework for the gut-urinary-prostatic axis and delineates when microbial and metabolite signalling meaningfully conditions prostate disease biology-and when it does not.