The impact of microbiome in urological diseases: a systematic review

  • Joseph K. M. Li
  • Peter K. F. Chiu
  • Chi-Fai NgEmail author
Urology - Review



The term microbiome is used to signify the ecological community of commensal, symbiotic, and pathogenic microorganisms that share our body space, in which there were increasing evidences to suggest that they might have potential roles in various medical conditions. While the study of microbiome in the urinary system is not as robust as the systems included in the Human Microbiome Project, there are still evidences in the literature showing that microbiome may have a role in urological diseases. Therefore, we would like to perform a systematic review on the topic and summarize the available evidence on the impact of microbiome on urological diseases.


This review was performed according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. After screening 589 abstracts and including additional studies (such as references from review papers), 76 studies were included for review and discussion.


Studies had suggested that there were correlations of microbiome of different body cavities (e.g., fecal, urinary and seminal fluid) with urological diseases. Also, different diseases would have different microbiome profile in different body cavities. Unfortunately, the studies on the association of microbiome and urological diseases were still either weak or inconsistent.


Studies suggested that there might be some relationship between microbiome and various urological diseases. However, further large-scale studies with control of confounding factors should be performed under a standardized methodology in order to have better understanding of the relationship. Also, more standardized reporting protocol for microbiome studies should be considered for better communications in future studies.


Microbiota Urology Prostate cancer Urolithiasis Lower urinary tract symptom 


Compliance with ethical standards

Conflict of interest

All authors declare that they have no conflict of interest related to this manuscript.

Human and animal rights statement

This article does not contain any studies with human participants or animals performed by any of the authors.


  1. 1.
    Savage DC (1977) Microbial ecology of the gastrointestinal tract. Annu Rev Microbiol 31(1):107–133. Google Scholar
  2. 2.
    Lederberg J, McCray A (2001) ’Ome Sweet’Omics—a genealogical treasury of words. Scientist 15:8Google Scholar
  3. 3.
    Whiteside SA, Razvi H, Dave S, Reid G, Burton JP (2015) The microbiome of the urinary tract–a role beyond infection. Nat Rev Urol 12(2):81–90. Google Scholar
  4. 4.
    Cho I, Blaser MJ (2012) The human microbiome: at the interface of health and disease. Nat Rev Genet 13(4):260–270. Google Scholar
  5. 5.
    Ursell LK, Metcalf JL, Parfrey LW, Knight R (2012) Defining the human microbiome. Nutr Rev 70(Suppl 1):S38–S44. Google Scholar
  6. 6.
    NIH HMP Working Group J, Peterson J, Garges S et al (2009) The NIH Human Microbiome Project. Genome Res 19(12):2317–2323. Google Scholar
  7. 7.
    Nelson DE, van der Pol B, Dong Q et al (2010) Characteristic male urine microbiomes associate with asymptomatic sexually transmitted infection. PLoS One 5(11):1–7. Google Scholar
  8. 8.
    Wolfe AJ, Toh E, Shibata N et al (2012) Evidence of uncultivated bacteria in the adult female bladder. J Clin Microbiol 50(4):1376–1383. Google Scholar
  9. 9.
    Fouts DE, Pieper R, Szpakowski S et al (2012) 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 10(1):174. Google Scholar
  10. 10.
    Khasriya R, Sathiananthamoorthy S, Ismail S et al (2013) Spectrum of bacterial colonization associated with urothelial cells from patients with chronic lower urinary tract symptoms. J Clin Microbiol 51(7):2054–2062. Google Scholar
  11. 11.
    Hilt EE, McKinley K, Pearce MM et al (2014) Urine is not sterile: use of enhanced urine culture techniques to detect resident bacterial flora in the adult female bladder. J Clin Microbiol 52(3):871–876. Google Scholar
  12. 12.
    Pearce MM, Hilt EE, Rosenfeld AB et al (2014) The female urinary microbiome: a comparison of women with and without urgency urinary incontinence. mBio 5(4):e01283-01214. Google Scholar
  13. 13.
    Moreno CE, Rodríguez P (2010) A consistent terminology for quantifying species diversity? Oecologia 163(2):279–282. Google Scholar
  14. 14.
    Garrett WS (2015) Cancer and the microbiota. Science 348(6230):80–86. Google Scholar
  15. 15.
    Liss MA, White JR, Goros M et al (2018) Metabolic biosynthesis pathways identified from fecal microbiome associated with prostate cancer. Eur Urol 74(5):575–582. Google Scholar
  16. 16.
    Amirian ES, Petrosino JF, Ajami NJ, Liu Y, Mims MP, Scheurer ME (2013) Potential role of gastrointestinal microbiota composition in prostate cancer risk. Infect Agent Cancer 8(1):42. Google Scholar
  17. 17.
    Pascale A, Marchesi N, Govoni S, Coppola A, Gazzaruso C (2019) The role of gut microbiota in obesity, diabetes mellitus, and effect of metformin: new insights into old diseases. Curr Opin Pharmacol 49:1–5. Google Scholar
  18. 18.
    Golombos DM, Ayangbesan A, O’Malley P et al (2018) The role of gut microbiome in the pathogenesis of prostate cancer: a prospective, pilot study. Urology 111:122–128. Google Scholar
  19. 19.
    Sfanos KS, Markowski MC, Peiffer LB et al (2018) Compositional differences in gastrointestinal microbiota in prostate cancer patients treated with androgen axis-targeted therapies. Prostate Cancer Prostatic Dis 21(4):539–548. Google Scholar
  20. 20.
    Yow MA, Tabrizi SN, Severi G et al (2017) Characterisation of microbial communities within aggressive prostate cancer tissues. Infect Agent Cancer 12:4. Google Scholar
  21. 21.
    Cavarretta I, Ferrarese R, Cazzaniga W et al (2017) The microbiome of the prostate tumor microenvironment. Eur Urol 72(4):625–631. Google Scholar
  22. 22.
    Feng Y, Ramnarine VR, Bell R et al (2019) Metagenomic and metatranscriptomic analysis of human prostate microbiota from patients with prostate cancer. BMC Genomics 20(1):146. Google Scholar
  23. 23.
    Alanee S, El-Zawahry A, Dynda D et al (2019) A prospective study to examine the association of the urinary and fecal microbiota with prostate cancer diagnosis after transrectal biopsy of the prostate using 16sRNA gene analysis. Prostate 79(1):81–87. Google Scholar
  24. 24.
    Shrestha E, White JR, Yu S-H et al (2018) Profiling the urinary microbiome in men with positive versus negative biopsies for prostate cancer. J Urol 199(1):161–171. Google Scholar
  25. 25.
    Xu W, Yang L, Lee P et al (2014) Mini-review: perspective of the microbiome in the pathogenesis of urothelial carcinoma. Am J Clin Exp Urol 2(1):57–61Google Scholar
  26. 26.
    Popović VB, Šitum M, Chow C-ET, Chan LS, Roje B, Terzić J (2018) The urinary microbiome associated with bladder cancer. Sci Rep 8(1):12157. Google Scholar
  27. 27.
    Wu P, Zhang G, Zhao J et al (2018) Profiling the urinary microbiota in male patients with bladder cancer in China. Front Cell Infect Microbiol 8:167. Google Scholar
  28. 28.
    Motzer RJ, Escudier B, McDermott DF et al (2015) Nivolumab versus everolimus in advanced renal-cell carcinoma. N Engl J Med 373(19):1803–1813. Google Scholar
  29. 29.
    Lopez-Beltran A, Henriques V, Cimadamore A et al (2018) The identification of immunological biomarkers in kidney cancers. Front Oncol 8:456. Google Scholar
  30. 30.
    Routy B, Le Chatelier E, Derosa L et al (2018) Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science 359(6371):91–97. Google Scholar
  31. 31.
    Yi M, Qin S, Chu Q, Wu K (2018) The role of gut microbiota in immune checkpoint inhibitor therapy. Hepatobiliary Surg Nutr 7(6):481–483. Google Scholar
  32. 32.
    Shigematsu Y, Inamura K (2018) Gut microbiome: a key player in cancer immunotherapy. Hepatobiliary Surg Nutr 7(6):479–480. Google Scholar
  33. 33.
    Gutierrez Millet V, Praga M, Miranda B et al (1985) Ureolytic Citrobacter freundii infection of the urine as a cause of dissolution of cystine renal calculi. J Urol 133(3):443–446Google Scholar
  34. 34.
    Stern JM, Moazami S, Qiu Y et al (2016) Evidence for a distinct gut microbiome in kidney stone formers compared to non-stone formers. Urolithiasis 44(5):399–407. Google Scholar
  35. 35.
    Suryavanshi MV, Bhute SS, Jadhav SD, Bhatia MS, Gune RP, Shouche YS (2016) Hyperoxaluria leads to dysbiosis and drives selective enrichment of oxalate metabolizing bacterial species in recurrent kidney stone endures. Sci Rep 6:34712. Google Scholar
  36. 36.
    Tang R, Jiang Y, Tan A et al (2018) 16S rRNA gene sequencing reveals altered composition of gut microbiota in individuals with kidney stones. Urolithiasis 46(6):503–514. Google Scholar
  37. 37.
    Allison MJ, Dawson KA, Mayberry WR, Foss JG (1985) Oxalobacter formigenes gen. nov., sp. nov.: oxalate-degrading anaerobes that inhabit the gastrointestinal tract. Arch Microbiol 141(1):1–7Google Scholar
  38. 38.
    Kaufman DW, Kelly JP, Curhan GC et al (2008) Oxalobacter formigenes may reduce the risk of calcium oxalate kidney stones. J Am Soc Nephrol 19(6):1197–1203. Google Scholar
  39. 39.
    Batagello CA, Monga M, Miller AW (2018) Calcium oxalate urolithiasis: a case of missing microbes? J Endourol 32(11):995–1005. Google Scholar
  40. 40.
    Lieske JC (2017) Probiotics for prevention of urinary stones. Ann Transl Med 5(2):29. Google Scholar
  41. 41.
    Cai T, Mazzoli S, Mondaini N et al (2012) The role of asymptomatic bacteriuria in young women with recurrent urinary tract infections: to treat or not to treat? Clin Infect Dis Off Publ Infect Dis Soc Am 55(6):771–777. Google Scholar
  42. 42.
    McDonald M, Kameh D, Johnson ME, Johansen TEB, Albala D, Mouraviev V (2017) A head-to-head comparative Phase II study of standard urine culture and sensitivity versus DNA next-generation sequencing testing for urinary tract infections. Rev Urol 19(4):213–220. Google Scholar
  43. 43.
    Mouraviev V, McDonald M (2018) An implementation of next generation sequencing for prevention and diagnosis of urinary tract infection in urology. Can J Urol 25(3):9349–9356Google Scholar
  44. 44.
    Darouiche RO, Green BG, Donovan WH et al (2011) Multicenter randomized controlled trial of bacterial interference for prevention of urinary tract infection in patients with neurogenic bladder. Urology. 78(2):341–346. Google Scholar
  45. 45.
    Darouiche RO, Thornby JI, Cerra-Stewart C, Donovan WH, Hull RA (2005) Bacterial interference for prevention of urinary tract infection: a prospective, randomized, placebo-controlled, double-blind pilot trial. Clin Infect Dis Off Publ Infect Dis Soc Am 41(10):1531–1534. Google Scholar
  46. 46.
    Sundén F, Håkansson L, Ljunggren E, Wullt B (2010) Escherichia coli 83972 bacteriuria protects against recurrent lower urinary tract infections in patients with incomplete bladder emptying. J Urol 184(1):179–185. Google Scholar
  47. 47.
    Biehl LM, Cruz Aguilar R, Farowski F et al (2018) Fecal microbiota transplantation in a kidney transplant recipient with recurrent urinary tract infection. Infection 46(6):871–874. Google Scholar
  48. 48.
    Wang T, Kraft CS, Woodworth MH, Dhere T, Eaton ME (2018) Fecal microbiota transplant for refractory Clostridium difficile infection interrupts 25-year history of recurrent urinary tract infections. Open Forum Infect Dis. 5(2):ofy016. Google Scholar
  49. 49.
    Tariq R, Pardi DS, Tosh PK, Walker RC, Razonable RR, Khanna S (2017) Fecal microbiota transplantation for recurrent Clostridium difficile infection reduces recurrent urinary tract infection frequency. Clin Infect Dis Off Publ Infect Dis Soc Am 65(10):1745–1747. Google Scholar
  50. 50.
    Antunes-Lopes T, Vale L, Coelho AM et al (2018) The role of urinary microbiota in lower urinary tract dysfunction: a systematic review. Eur Urol Focus 1:1. Google Scholar
  51. 51.
    Siddiqui H, Lagesen K, Nederbragt AJ, Jeansson SL, Jakobsen KS (2012) Alterations of microbiota in urine from women with interstitial cystitis. BMC Microbiol 12:205. Google Scholar
  52. 52.
    Nickel JC, Stephens-Shields AJ, Landis JR et al (2019) A culture-independent analysis of the microbiota of female interstitial cystitis/bladder pain syndrome participants in the MAPP research network. J Clin Med. Google Scholar
  53. 53.
    Abernethy MG, Rosenfeld A, White JR, Mueller MG, Lewicky-Gaupp C, Kenton K (2017) Urinary microbiome and cytokine levels in women with interstitial cystitis. Obstet Gynecol 129(3):500–506. Google Scholar
  54. 54.
    Nickel JC, Stephens A, Landis JR et al (2016) Assessment of the lower urinary tract microbiota during symptom flare in women with urologic chronic pelvic pain syndrome: a MAPP network study. J Urol 195(2):356–362. Google Scholar
  55. 55.
    Braundmeier-Fleming A, Russell NT, Yang W et al (2016) Stool-based biomarkers of interstitial cystitis/bladder pain syndrome. Sci Rep 6:26083. Google Scholar
  56. 56.
    Ivanov IB, Kuzmin MD, Gritsenko VA (2009) Microflora of the seminal fluid of healthy men and men suffering from chronic prostatitis syndrome. Int J Androl 32(5):462–467. Google Scholar
  57. 57.
    Mändar R, Punab M, Korrovits P et al (2017) Seminal microbiome in men with and without prostatitis. Int J Urol Off J Jpn Urol Assoc 24(3):211–216. Google Scholar
  58. 58.
    Nickel JC, Stephens A, Landis JR et al (2015) Search for microorganisms in men with urologic chronic pelvic pain syndrome: a culture-independent analysis in the MAPP research network. J Urol 194(1):127–135. Google Scholar
  59. 59.
    Shoskes DA, Altemus J, Polackwich AS, Tucky B, Wang H, Eng C (2016) 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 92:26–32. Google Scholar
  60. 60.
    Magri V, Boltri M, Cai T et al (2019) Multidisciplinary approach to prostatitis. Arch Ital Urol Androl Organo Uff Soc Ital Ecogr Urol E Nefrol 90(4):227–248. Google Scholar
  61. 61.
    Shoskes DA, Wang H, Polackwich AS, Tucky B, Altemus J, Eng C (2016) Analysis of gut microbiome reveals significant differences between men with chronic prostatitis/chronic pelvic pain syndrome and controls. J Urol 196(2):435–441. Google Scholar
  62. 62.
    Mändar R, Punab M, Borovkova N et al (2015) Complementary seminovaginal microbiome in couples. Res Microbiol 166(5):440–447. Google Scholar
  63. 63.
    Groah SL, Pérez-Losada M, Caldovic L et al (2016) Redefining healthy urine: a cross-sectional exploratory metagenomic study of people with and without bladder dysfunction. J Urol 196(2):579–587. Google Scholar
  64. 64.
    Brubaker L, Nager CW, Richter HE et al (2014) Urinary bacteria in adult women with urgency urinary incontinence. Int Urogynecol J 25(9):1179–1184. Google Scholar
  65. 65.
    Pearce MM, Zilliox MJ, Rosenfeld AB et al (2015) The female urinary microbiome in urgency urinary incontinence. Am J Obstet Gynecol 213(3):347.e1–347.e11. Google Scholar
  66. 66.
    Fok CS, Gao X, Lin H et al (2018) Urinary symptoms are associated with certain urinary microbes in urogynecologic surgical patients. Int Urogynecol J 29(12):1765–1771. Google Scholar
  67. 67.
    Thomas-White KJ, Kliethermes S, Rickey L et al (2017) Evaluation of the urinary microbiota of women with uncomplicated stress urinary incontinence. Am J Obstet Gynecol 216(1):55.e1–55.e16. Google Scholar
  68. 68.
    Karstens L, Asquith M, Davin S et al (2016) Does the urinary microbiome play a role in urgency urinary incontinence and its severity? Front Cell Infect Microbiol 6:78. Google Scholar
  69. 69.
    Wu P, Chen Y, Zhao J et al (2017) Urinary microbiome and psychological factors in women with overactive bladder. Front Cell Infect Microbiol 7:488. Google Scholar
  70. 70.
    Thomas-White KJ, Hilt EE, Fok C et al (2016) Incontinence medication response relates to the female urinary microbiota. Int Urogynecol J 27(5):723–733. Google Scholar
  71. 71.
    Bajic P, Van Kuiken ME, Burge BK et al (2018) Male bladder microbiome relates to lower urinary tract symptoms. Eur Urol Focus 1:1. Google Scholar
  72. 72.
    Jarvi K, Lacroix JM, Jain A, Dumitru I, Heritz D, Mittelman MW (1996) Polymerase chain reaction-based detection of bacteria in semen. Fertil Steril 66(3):463–467Google Scholar
  73. 73.
    Kiessling AA, Desmarais BM, Yin H-Z, Loverde J, Eyre RC (2008) Detection and identification of bacterial DNA in semen. Fertil Steril 90(5):1744–1756. Google Scholar
  74. 74.
    Hou D, Zhou X, Zhong X et al (2013) Microbiota of the seminal fluid from healthy and infertile men. Fertil Steril 100(5):1261–1269. Google Scholar
  75. 75.
    Baud D, Pattaroni C, Vulliemoz N, Castella V, Marsland BJ, Stojanov M (2019) Sperm microbiota and its impact on semen parameters. Front Microbiol 10:234. Google Scholar
  76. 76.
    Chen H, Luo T, Chen T, Wang G (2018) Seminal bacterial composition in patients with obstructive and non-obstructive azoospermia. Exp Ther Med 15(3):2884–2890. Google Scholar
  77. 77.
    Alfano M, Ferrarese R, Locatelli I et al (2018) Testicular microbiome in azoospermic men-first evidence of the impact of an altered microenvironment. Hum Reprod Oxf Engl 33(7):1212–1217. Google Scholar

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© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.SH Ho Urology Centre, Department of SurgeryThe Chinese University of Hong KongShatinHong Kong

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