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

Prostate Cancer and Prostatic Diseases (2025)Cite this article

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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.

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Fig. 1: PRISMA 2020 flow diagram.
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Author information

Author notes

  1. These authors contributed equally: Alfredo Distante, Davide Garino.

Authors and Affiliations

  1. Division of Urology, Cochin Hospital, AP-HP, Paris Cité University, Paris, France

    Alfredo Distante

  2. Division of Urology, Cardinale Panico Tricase City Hospital, Tricase, Italy

    Alfredo Distante

  3. Department of Oncology, Division of Urology, San Luigi Hospital, Orbassano, Italy

    Davide Garino

  4. Department of Urology, University Hospital Southampton NHS Trust, Southampton, SO, UK

    Clara Cerrato

  5. Department of Urology, Hospital Universitario Politechnic La Fe, Valencia, Spain

    Javier Perez-Ardavin & Francisco Quereda Flores

  6. IBD UNIT, CEMAD Centro Malattie dell’Apparato Digerente, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario Gemelli IRCCS, Roma, Italy

    Loris Lopetuso

  7. Dipartimento di Scienze della Vita, della Salute e delle Professioni Sanitarie Università degli Studi Link, Roma, Italy

    Loris Lopetuso

  8. Department of Urology, Mount Sinai Icahn School of Medicine, Elmhurst/Queens Hospitals, New York, USA

    Maria Carmen Mir

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Contributions

AD and DG performed the systematic review, extracted and analyzed the data, and drafted the manuscript. Both authors contributed equally as first authors. MCM conceived and designed the study, supervised the project, provided critical revisions, and approved the final version of the manuscript. JPA, FQF, and CC contributed to the writing and critical revision of the manuscript. LL provided expertise on microbiota, and contributed to the interpretation of the findings.

Corresponding author

Correspondence to Maria Carmen Mir.

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Distante, A., Garino, D., Cerrato, C. et al. The role of the human microbiome in prostate cancer: a systematic review from diagnosis to treatment. Prostate Cancer Prostatic Dis (2025). https://doi.org/10.1038/s41391-025-01028-w

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