An introduction to the study of human urinary microbiome

Česká verzia

Authors: Jan Hrbáček ¹; Vítězslav Hanáček ¹; Pavel Čermák ²; Daniel Morais ³; Roman Zachoval ¹
Authors place of work: Urologická klinika 3. LF UK a Thomayerovy nemocnice, Praha ¹; Oddělení klinické mikrobiologie, Thomayerova nemocnice, Praha ²; Mikrobiologický ústav Akademie věd České republiky, Praha ³
Published in the journal: Ces Urol 2021; 25(1): 17-26
Category: Review article

Summary

Hrbáček J, Hanáček V, Čermák P, Morais D, Zachoval R. An introduction to the study of human urinary microbiome.

The assumption of healthy urine being sterile has been contradicted recently when the existence of urinary microbiota (UM) was revealed. Extended quantitative urine culture is based on longer incubation times in a wide selection of diverse growth conditions; bacteria are detected even in samples reported as negative by the standard urine culture protocol. Next‑generation sequencing helps with taxonomic assignment of prokaryotic DNA fragments according to the sequence in hypervariable regions of the 16S rRNA gene. Human UM is composed of the phyla Proteobacteria, Firmicutes, Bacteroidetes and Actinobacteria. Female UM is dominated by the genus Lactobacillus, male urotypes have not been assigned with certainty to date. Changes in UM have been associated with functional disorders of the genitourinary tract (lower urinary tract symptoms, urge urinary incontinence, neurogenic bladder dysfunction, chronic kidney disease), chronic pelvic pain syndrome, interstitial cystitis and even with urinary bladder cancer. UM may potentially play many a role; what they are is a matter of ongoing research. UM might be a useful tool in the diagnostics and therapy of disease.

Keywords:

Extended quantitative urine culture – genitourinary system – human microbiome – next generation sequencing

Zdroje

1. Thomas‑White K, Brady M, Wolfe AJ, Mueller ER. The Bladder Is Not Sterile: History and Current Discoveries on the Urinary Microbiome. Curr Bladder Dysfunct Rep 2016; 11(1): 18–24.

2. Khasriya R, Sathiananthamoorthy S, Ismail S, et al. Spectrum of Bacterial Colonization Associated with Urothelial Cells from Patients with Chronic Lower Urinary Tract Symptoms. J Clin Microbiol. 2013; 51(7): 2054–2062.

3. Siddiqui H, Nederbragt AJ, Lagesen K, Jeansson SL, Jakobsen KS. Assessing diversity of the female urine microbiota by high throughput sequencing of 16S rDNA amplicons. BMC Microbiol. 2011; (11): 1–12.

4. The Human Microbiome Project Consortium: Structure, function and diversity of the healthy human microbiome. Nature [Internet] 2012; 486: 207–214. Dostupné z: http://dx.doi.org/10.1038/nature11234, 13. 11. 2020.

5. Zwinsová B, Brychtová V, Hrivňáková M, et al. Vliv mikrobiomu na vznik a vývoj kolorektálního karcinomu. Klin Onkol 2019; 32(4): 261–269.

6. Wolfe AJ, Brubaker L. „Sterile Urine“ and the Presence of Bacteria. Eur Urol. 2015; 68(2): 173–174.

7. Whiteside SA, Razvi H, Dave S, Reid G, Burton JP. The microbiome of the urinary tract – a role beyond infection. Nat Rev Urol [Internet] 2015; 12(2): 81–90. Dostupné z: http://dx.doi.org/10.1038/nrurol.2014.361, 3. 5. 2019.

8. Hilt EE, McKinley K, Pearce MM, et al. Urine Is Not Sterile: Use of Enhanced Urine Culture Techniques To Detect Resident Bacterial Flora in the Adult Female Bladder. J Clin Microbiol 2014; 52(3): 871–876.

9. Price TK, Dune T, Hilt EE, et al. The Clinical Urine Culture: Enhanced Techniques Improve Detection of Clinically Relevant Microorganisms. J Clin Microbiol. 2016; 54(5): 1216–1222.

10. Alberts B, Bray D, Johnson A. DNA Technology. In: Essential Cell Biology 1998; 13–46.

11. Pollock J, Glendinning L, Wisedchanwet T, Watson M. The madness of microbiome: Attempting to find consensus „Best Practice“ for 16S microbiome studies. Appl Environ Microbiol. 2018; 84(7): e02627–17.

12. Illumina.com [Internet]. Dostupné z: https://www.illumina.com/systems/sequencing‑platforms/ miseq. html, 21. 11. 2020.

13. Fukuda K, Ogawa M, Taniguchi H, Saito M. Molecular Approaches to Studying Microbial Communities: Targeting the 16S Ribosomal RNA Gene. J UOEH 2016; 38(3): 223–232.

14. Mueller ER, Wolfe AJ, Brubaker L. Female urinary microbiota. Curr Opin Urol. 2017; 27(3): 282–286.

15. Vetrovsky T, Baldrian P, Morais D. SEED 2: a user‑friendly platform for amplicon high‑throughput sequencing data analyses. Bioinformatics 2018; 34(13): 2292–2294.

16. Wu P, Zhang G, Zhao J, et al. Profiling the Urinary Microbiota in Male Patients With Bladder Cancer in China. Front Cell Infect Microbiol 2018; 8: 167.

17. Pederzoli F, Ferrarese R, Amato V, et al. Sex‑specific Alterations in the Urinary and Tissue Microbiome in Therapy‑naïve Urothelial Bladder Cancer Patients. Eur Urol Oncol 2020; 3(6): 784–788.

18. Morand A, Cornu F, Dufour JC. Human Bacterial Repertoire of the Urinary Tract: a Potential Paradigm Shift. J Clin Microbiol 2019; 57(3): e00675–18.

19. Thomas‑White KJ, Hilt EE, Fok C. Incontinence Medication Response Relates to the Female Urinary Microbiota. Int Urogynecol J. 2016; 27(5): 723–733.

20. Groah SL, Pérez‑Losada M, Caldovic L, et al. Redefining Healthy Urine: A Cross‑Sectional Exploratory Metagenomic Study of People With and Without Bladder Dysfunction. J Urol 2016; 196(2): 579–587.

21. Thomas‑White K, Forster SC, Kumar N, et al. Culturing of female bladder bacteria reveals an interconnected urogenital microbiota. Nat Commun [Internet] 2018; (9): 1557. Dostupné z: http://dx.doi.org/10.1038/ s41467-018-03968-5, 13. 11. 2020.

22. Shrestha E, White JR, Yu S, et al. Profiling the Urinary Microbiome in Men with Positive versus Negative Biopsies for Prostate Cancer. J Urol 2018; 199: 161–171.

23. Lewis DA, Brown R, Williams J, et al. The human urinary microbiome; bacterial DNA in voided urine of asymptomatic adults. Front Cell Infect Microbiol [Internet] 2013; 3: 1–14. Dostupné z: http://journal. frontiersin.org/article/10.3389/fcimb.2013.00041/abstract, 3. 5. 2019.

24. Kramer H, Kuffel G, Thomas‑White K, et al. Diversity of the midstream urine microbiome in adults with chronic kidney disease. Int Urol Nephrol 2018; 50(6): 1123–1130.

25. Wolfe AJ, Toh E, Shibata N, et al. Evidence of Uncultivated Bacteria in the Adult Female Bladder. J Clin Microbiol. 2012; 1376–1383.

26. Bajic P, Kuiken ME van, Burge BK, et al. Male Bladder Microbiome Relates to Lower Urinary Tract Symptoms. Eur Urol Focus 2020; 15(6): 376–382.

27. Popović VB, Šitum M, Chow CT, Chan LS. The urinary microbiome associated with bladder cancer. Sci Rep. 2018; 8: 12157.

28. Shoskes DA, Altemus J, Polackwich AS, Tucky B, Wang H. 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.

29. Siddiqui H, Lagesen K, Nederbragt AJ, Jeansson SL, Jakobsen KS. Alterations of microbiota in urine from women with interstitial cystitis. BMC Microbiol [Internet] 2012; 12: 205. Dostupné z: http://www. biomedcentral.com/1471-2180/12/205, 3. 5. 2019.

30. Nickel JC, Stephens A, Landis JR, et al. Assessment of the Lower Urinary Tract Microbiota during Symptom Flare in Women with Urologic Chronic Pelvic Pain Syndrome: A MAPP Network Study. J Urol. 2016; 195(2): 356–362.

31. Thomas‑White KJ, Kliethermes S, Rickey L. Evaluation of the Urinary Microbiota of Women With Uncomplicated Stress Urinary Incontinence. Am J Obs Gynecol. 2017; 216(1).

32. Fouts D, Pieper R, Szpakowski S. 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): 55.e1–55.e16.

33. Wu JF, Muthusamy A, Al‑Ghalith GA, Dan K. Urinary microbiome associated with chronic allograft dysfunction in kidney transplant recipients. Clin Transplant 2018; (32): e13436.

34. Cai T, Mazzoli S, Lanzafame P, et al. Asymptomatic Bacteriuria in Clinical Urological Practice: Preoperative Control of Bacteriuria and Management of Recurrent UTI. Pathogens [Internet] 2016; 5(1): 4. Dostupné z: http://www.mdpi.com/2076-0817/5/1/4, 20. 11. 2018

35. Rani A, Ranjan R, McGee HS, et al. A diverse virome in kidney transplant patients contains multiple viral subtypes with distinct polymorphisms. Sci Rep 2016; (6): 33327.

36. Garretto A, Thomas‑White K, Wolfe AJ, Putonti C. Detecting viral genomes in the female urinary microbiome. J Gen Virol. 2018; 99: 1141–1146.

37. Ackerman AL, Underhill DM. The mycobiome of the human urinary tract: Potential roles for fungi in urology. Ann Transl Med 2017; 5(2): 1–12.

38. Kim BR, Shin J, Guevarra RB, et al. Deciphering diversity indices for a better understanding of microbial communities. J Microbiol Biotechnol 2017; 27(12): 2089–2093.