Implications of the Genitourinary Microbiota in Prostatic Disease
Purpose of Review
To summarize recent investigation into associations between the genitourinary microbiota and prostatic disease.
The genitourinary tract is not sterile. There are microbial communities (microbiota) in each niche of the genitourinary tract including the bladder, prostate, and urethra, which have been the subject of increasing scientific interest. Investigators have utilized several unique methods to study them, resulting in a highly heterogeneous body of literature. To characterize these genitourinary microbiota, diverse clinical specimens have been analyzed, including urine obtained by various techniques, seminal fluid, expressed prostatic secretions, and prostatic tissue. Recent studies have attempted to associate the microbiota detected from these samples with urologic disease and have implicated the genitourinary microbiota in many common conditions, including benign prostatic hyperplasia (BPH), prostate cancer, and chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS).
In this review, we summarize the recent literature pertaining to the genitourinary microbiota and its relationship to the pathophysiology and management of three common prostatic conditions: BPH, prostate cancer, and CP/CPPS.
KeywordsMicrobiota Microbiome Prostate BPH Prostate cancer Chronic prostatitis
We would like to thank the members of the Loyola Urinary Education and Research Collaborative (LUEREC) for their contributions to the work described.
AJW has been supported by National Institutes of Health grants R01 DK104718, 2 U10 HD41250, U01 DK58229, R21 DK097435, R56 DK104718, and P20 DK108268, a translational grant from the Falk Foundation, and by RFC LU206998 from Loyola University Chicago. AJW also has received funding for an Investigator Initiated Study VESI-12D01 from Astellas Scientific and Medical Affairs, Inc. AVF and LB have been supported by Loyola University Chicago RFC LU207906. LB has also been supported by the Interstitial Cystitis Association.
Compliance with Ethical Standards
Conflict of Interest
Petar Bajic and Chirag P. Doshi each declare no potential conflicts of interest.
Ryan A. Dornbier, Ahmer V. Farooq, and Larissa Bresler report intramural funding from Loyola University Medical Center Research Committee.
Alan J. Wolfe reports grants from Astellas Scientific and Medical Affairs and Kimberly Clark Corporation.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
The funding sources have had no role in design or conduct of the studies; collection, management, analysis, and interpretation of the data; or in preparation, review, or approval of this or any other manuscript.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
- 3.U.S. Department of Health and Human Services, Centers for Disease Control and Prevention and National Cancer Institute. U.S. Cancer Statistics Working Group. U.S. Cancer Statistics Data Visualizations Tool, based on November 2017 submission data (1999–2015). 2018. Available at: www.cdc.gov/cancer/dataviz. Accessed 16 Mar 2019.
- 4.Bowen DK, Dielubanza E, Schaeffer AJ. Chronic bacterial prostatitis and chronic pelvic pain syndrome. BMJ Clin Evid. 2015;2015:1802.Google Scholar
- 7.•• Shrestha E, White JR, Yu SH, Kulac I, Ertunc O, de Marzo AM, et al. Profiling the urinary microbiome in men with positive versus negative biopsies for prostate cancer. J Urol. 2018;199:161–71 A recent study demonstrating increase in uropathogenic bacteria in cancerous prostate tissue. This study leads to additional hypotheses regarding the nature of bacterial inflammation as a determinant of prostate cancer. PubMedGoogle Scholar
- 26.•• Bajic P, van Kuiken ME, Burge BK, Kirshenbaum EJ, Joyce CJ, Wolfe AJ, et al. Male bladder microbiome relates to lower urinary tract symptoms. Eur Urol Focus. 2018. https://doi.org/10.1016/j.euf.2018.08.001 This study is the first study to demonstrate an association between the urinary microbiome in men and lower urinary tract symptoms. Also important in establishing the difference between voided and catheterized urine collection in men. It lays groundwork for additional investigation in the the male urinary microbiome.
- 28.Fouts DE, Pieper R, Szpakowski S, Pohl H, Knoblach S, Suh MJ, et al. Integrated next-generation sequencing of 16S rDNA and metaproteomics differentiate the healthy urine microbiome from asymptomatic bacteriuria in neuropathic bladder associated with spinal cord injury. J Transl Med. 2012;10:174.PubMedPubMedCentralGoogle Scholar
- 32.Pearce MM, et al. The female urinary microbiome in urgency urinary incontinence. Am J Obstet Gynecol. 2015;213(347):e1–11.Google Scholar
- 33.• Price TK, Dune T, Hilt EE, Thomas-White KJ, Kliethermes S, Brincat C, et al. The clinical urine culture: enhanced techniques improve detection of clinically relevant microorganisms. J Clin Microbiol. 2016;54:1216–22 This study further expands our knowledge of urine culture protocols and the expanded quantitative urine culture (EQUC) to identify and isolate live bacteria that would not otherwise be detected by standard clinical cultures. PubMedPubMedCentralGoogle Scholar
- 40.• Thomas-White KJ, Gao X, Lin H, Fok CS, Ghanayem K, Mueller ER, et al. Urinary microbes and postoperative urinary tract infection risk in urogynecologic surgical patients. Int Urogynecol J. 2018;29:1797–805 In this study, the authors showed that certain preoperative urinary microbiome profiles in women lead to increased risk of postoperative, symptomatic UTI. Moreover, abundance of Lactobacillus iners was associated with protection against UTI development. This may have an important corollary in men in that dysbiosis of the urinary microbiome may lead to increased risk of disease. PubMedGoogle Scholar
- 45.• Yu H, et al. Urinary microbiota in patients with prostate cancer and benign prostatic hyperplasia. Arch Med Sci. 2015;11:385–94 In this study, investigators showed a difference in bacterial flora in men with and without prostate cancer. This study utilized expressed prostatic secretions as a sample type, introducing a less invasive way to detect prostatic microbiota outside of invasive tissue sampling. PubMedPubMedCentralGoogle Scholar
- 47.• Cavarretta I, et al. The microbiome of the prostate tumor microenvironment. Eur Urol. 2017;72:625–31 This study examines the difference in microbial communities of various prostatic pathologies in patients with prostate cancer. In doing so, it suggests the microbiota to be a possible source of carcinogenesis and a potential therapeutic target. PubMedGoogle Scholar
- 49.• Feng Y, et al. Metagenomic and metatranscriptomic analysis of human prostate microbiota from patients with prostate cancer. BMC Genomics. 2019;20:146 The importance of this study relates to the use of advanced miciobial detection methods with metagenomic and metascriptomic profiling for detecting the non-“sterile” environment in the prostate and prostate tumor tissue. PubMedPubMedCentralGoogle Scholar
- 50.•• Mändar R, Punab M, Korrovits P, Türk S, Ausmees K, Lapp E, et al. Seminal microbiome in men with and without prostatitis. Int J Urol. 2017;24:211–6 In this study, the authors demonstrate a different microbial profile in patients with CP/CPPS compared to controls. Importantly, there was a relative depletion of the genus Lactobacillus. These findings are similar to previous studies in women suggesting the importance of Lactobacillus in the genitourinary microbiome. PubMedGoogle Scholar
- 51.• Shoskes DA, Altemus J, Polackwich AS, Tucky B, Wang H, Eng C. The urinary microbiome differs significantly between patients with chronic prostatitis/chronic pelvic pain syndrome and controls as well as between patients with different clinical phenotypes. Urology. 2016;92:26–32 Additional evidence suggesting a difference in microbiota composition in patients with and without CP/CPPS. This study used voided urine. PubMedGoogle Scholar
- 52.Russo GI, Urzì D, Cimino S. Epidemiology of LUTS and BPH. Lower Urinary Tract Symptoms and Benign Prostatic Hyperplasia; 2018. p. 1–14. https://doi.org/10.1016/b978-0-12-811397-4.00001-9.CrossRefGoogle Scholar
- 53.McConnell JD, et al. The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia. N Engl J Med. 2003;349:2387–98.Google Scholar
- 54.Roehrborn CG, Siami P, Barkin J, Damião R, Major-Walker K, Nandy I, et al. The effects of combination therapy with dutasteride and tamsulosin on clinical outcomes in men with symptomatic benign prostatic hyperplasia: 4-year results from the CombAT study. Eur Urol. 2010;57:123–31.Google Scholar
- 55.McVary KT, Roehrborn CG, Avins AL, Barry MJ, Bruskewitz RC, Donnell RF, et al. Update on AUA guideline on the management of benign prostatic hyperplasia. J Urol. 2011;185:1793–803.Google Scholar
- 56.Djavan B. The correlation between inflammation, BPH and prostate cancer. Eur Urol Suppl. 2009;8:863–4.Google Scholar
- 58.Kashyap M, Pore S, Wang Z, Gingrich J, Yoshimura N, Tyagi P. Inflammasomes are important mediators of prostatic inflammation associated with BPH. J Inflamm. 2015;12:37.Google Scholar
- 59.Jiang Y-H, Lin VC-H, Liao C-H, Kuo H-C. International prostatic symptom score — voiding/storage subscore ratio in association with total prostatic volume and maximum flow rate is diagnostic of bladder outlet-related lower urinary tract dysfunction in men with lower urinary tract symptoms. PLoS One. 2013;8:e59176.PubMedPubMedCentralGoogle Scholar
- 60.Liao C-H, Kuo H-C. Use of the international prostate symptom score voiding-to-storage subscore ratio in assessing lower urinary tract symptoms. Tzu Chi Med J. 2014;26:61–3.Google Scholar
- 61.Chuang F-C, Hsiao S-M, Kuo H-C. The overactive bladder symptom score, international prostate symptom score–storage subscore, and urgency severity score in patients with overactive bladder and hypersensitive bladder: which scoring system is best? Int Neurourol J. 2018;22:99–106.PubMedPubMedCentralGoogle Scholar
- 77.Meares EM, Stamey TA. Bacteriologic localization patterns in bacterial prostatitis and urethritis. Investig Urol. 1968;5:492–518.Google Scholar
- 86.Berger RE, Ciol MA, Rothman I, Turner JA. Pelvic tenderness is not limited to the prostate in chronic prostatitis/chronic pelvic pain syndrome (CPPS) type IIIA and IIIB: comparison of men with and without CP/CPPS. BMC Urol. 2007;7:17.Google Scholar
- 91.Miller-Ensminger T, Garretto A, Brenner J, Thomas-White K, Zambom A, Wolfe AJ, et al. Bacteriophages of the urinary microbiome. J Bacteriol. 2018;200(7):e00738–17. https://doi.org/10.1128/JB.00738-17
- 92.Bang C, Schmitz RA. Archaea: forgotten players in the microbiome. Emerg Top Life Sci. 2018;2:459–68.Google Scholar