The Gut-Prostate axis in chronic Prostatitis/Chronic Pelvic pain syndrome: Mechanisms, evidence gaps, and biomarker-stratified translation.

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a heterogeneous disorder traditionally framed around local prostate, pelvic-floor, neurological, and psychosocial factors. Emerging evidence suggests that gut dysbiosis may contribute to CP/CPPS in a subset of patients through barrier dysfunction, immune priming, microbial metabolites, and neuroimmune modulation. We propose a Dual-Hit Permissive Model in which gut-derived systemic immunometabolic priming must converge with prostate-local or pelvic permissive cues before organ-localized inflammation and chronic pain can be sustained. We distinguish direct human CP/CPPS evidence from animal prostatitis models, contextual prostate-disease evidence, and hypothesis-generating mechanisms. Ectopic mucosal addressins, prostate-specific vascular "address codes," and microbial-prostate molecular mimicry remain testable hypotheses rather than established mechanisms. Future work should prioritize biomarker-stratified, target-engagement studies to validate immunometabolic, tissue-localization, and neuroimmune checkpoints before gut-directed interventions are broadly translated into CP/CPPS care.