The role of the human microbiome in prostate cancer: a systematic review from diagnosis to treatment

Abstract

Background: Prostate cancer (PC) heterogeneity and treatment resistance remain major clinical challenges, with emerging evidence implicating the microbiome as a key modulator of disease pathogenesis. While microbial dysbiosis has been linked to PC diagnosis, progression, and therapeutic outcomes, the mechanisms underlying these associations are poorly understood. This review synthesizes current evidence on the diagnostic, prognostic, and therapeutic potential of the microbiome in PC.

Methods: A systematic search of PubMed, Embase, and Cochrane Central Register of Controlled Trials (through April 2024) was conducted following PRISMA guidelines (PROSPERO: CRD42024534899). Controlled and observational studies investigating microbial roles in PC diagnosis (e.g., ISUP grading group), prognosis, or treatment response were included. Data extraction and quality assessment used the QUIPS tool. From 810 screened records, 42 studies met inclusion criteria.

Results: Distinct microbial profiles differentiated PC from controls, with Mycoplasma genitalium and Staphylococcus spp. enriched in prostate tumors (3.1- and 2.7-fold, respectively) and correlated with inflammation (IL-6: r = 0.38, p = 0.002). Urinary microbiota showed diagnostic potential (sensitivity: 58-82%), though sampling methods influenced variability. Prognostically, Betaproteobacteria gut enrichment predicted earlier castration-resistant progression (5.2 months; HR 1.8, 95% CI 1.3-2.5), while ADT-induced dysbiosis (e.g., Klebsiella overgrowth) accelerated resistance (2.1-fold risk). Therapies altered microbial ecology: radiotherapy depleted Bacteroides (linked to proctitis; OR 3.1), and immunotherapy responders harbored higher Akkermansia muciniphila. Microbial androgen synthesis and endotoxin production emerged as resistance mechanisms.

Conclusions: The microbiome influences PC detection, aggressiveness, and treatment efficacy through direct (tissue-resident) and indirect (gut-derived) mechanisms. Standardized profiling and microbiome-modulating strategies (e.g., probiotics during ADT) may personalize management. Prospective trials are needed to validate causality and translate microbial biomarkers into clinical practice.