Virusuria as a component of the urine microbiota and its significance for assessing the health of the urinary tract: a descriptive clinical study


Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

Aim. To determine the frequency of occurrence of opрortunistic pathogenic bacterial flora and viral pathogens in the urine of healthy people with the establishment of the association between them. Materials and methods. 40 healthy sexually active women and men were examined, which are divided by gender into equivalent groups: Group I - healthy women (n=19), Group II - healthy men (n=21). The age of the subjects ranged from 20 to 25 years, the average age was 22.4±1.2 years. In both groups, the average portion of morning urine was taken for a study after a proper hygienic procedure with self-urination of the subjects in a sterile plastic container (Sterile Uricol for urine sample collection «HiMedia»). In addition to the nutrient media regulated by the Clinical Guidelines, additional HiMedia chromogenic media were used to cultivate facultative anaerobic (FAB) and non-clostridial anaerobic bacteria (NAB). Detection of viruses was performed by PCR with detection in «real time». DNA isolation was carried out by the sorption method using the AmpliPrime DNA-Sorb-B («NextBio») kit from urine samples, with preliminary concentration. Results. In all 40 cases, normative leukocyturia was detected in the urine. According to the results ofbacteriological examination ofurine, healthy men and women in all cases found aerobic-anaerobic associations. Coagulase-negative staphylococci (CNS) and Corynebacterium spp. Dominated in the cluster of aerobic taxa of microbiota. (75.0%, 55.0% respectively). The spectrum of CNS was represented by five species: S.epidermidis (30.0%), S.haemolyticus (27.5%), and S.warneri (25.0%), S.saprophyticus and S.lentus (15.0%). Enterococcus spp. were recorded in the urine in 32.5% of cases. Representatives of the Enterobacteriaceae family were represented by 4 taxa: E. coli (10.0%), Klebsiella spp., Proteus spp. (5.0% each), Enterobacter spp., Citrobacter spp. (2.5%). In a cluster of anaerobic bacteria in the urine, Eubacterium spp. (60.0%) and almost half of healthy individuals recorded Lactobacillus spp. and Peptococcus spp. (42.5% each). When analyzing the frequencies of detection of various microbiota taxa, it was found that women significantly more frequently recorded urine Corynebacterium spp., Eubacterium spp. and Lactobacillus spp., as well as Enterococcus spp. and Peptococcus spp. Peptostreptococcus spp. and Veillonella spp. were significantly more often determined (p<0.05) in the urine of men. HHV6 (10.0%), HPV18 and B19 parvovirus (2,5%) were determined in the urine of healthy people. It should be noted that the studied viruses were more often recorded in men, in particular, HPV18 and parvovirus B19 - only in men, and HHV6 - more often in men (7.5%), less often in women (2.5%). Significant associations of some genera of microorganisms with the sex of the participants were revealed for E. faecalis and Lactobacillus spp., which were more often found in the urine of healthy women Reliably significant associations were found for three taxa: viruses HPV6, HPV18 and parvoviruses B19 (16.7%) were determined in the presence of Bacteroides spp., Bifidobacterium spp., and Prevotella spp., in urine. Accordingly, in 83.3% of cases, these viruses were detected in the absence of the above-listed taxa of microorganisms in the urine. Conclusions. The normal urinary microbiota of healthy women and men has differences: Lactobacillus spp and Candida spp are absent in the urine of men while Streptococcus spp in urine of women. HHV6, HPV18, parvoviruses B19 are found in urine of healthy people and more often in men. Data about the virobiota and microbiota of urine in healthy people can highlight on the pathogenesis of urinary tract infections of various localization and develop targeted approaches in personalized therapy of this group of diseases.

Full Text

Restricted Access

About the authors

Yu. L Naboka

Rostov State Medical University

Email: nagu22@mail.ru

I. A. Gudima

Rostov State Medical University

Email: nagu22@mail.ru

S. V Mordanov

Rostov State Medical University

Email: labmed@mail.ru

D. V Krakhotkin

Rostov State Medical University

Email: den_surgeon@mail.ru

A. V Il’yash

Rostov State Medical University

Email: annailyash@yandex.ru

M. I Kogan

Rostov State Medical University

Email: dept_kogan@mail.ru

D. V. Sizyakin

Rostov State Medical University

Email: dsiziakin@mail.ru

Kh. S Ibishev

Rostov State Medical University

Email: ibishev22@mail.ru

References

  1. Thomas-White K., Brady M., Wolfe A.J., Mueller E.R. The bladder is not sterile: history and current discoveries on the urinary microbiome. Curr Bladder Dysfunct Rep. 2016; 11( 1): 18-24. doi: 10.1007/s11884-016-0345-8.
  2. Wolfe A.J., Brubaker L. Sterile Urine and the Presence of Bacteria. Eur Urol. 2015;68(2):173-174. doi: 10.1016/j.eururo.2015.02.041.
  3. Karstens L., Asquith M., Davin S., Stauffer P., Fair D., Gregory W.T., Rosenbaum J.T., McWeeney S.K., NardosR. Does the Urinary Microbiome Play a Role in Urgency Urinary Incontinence and Its Severity? Front Cell Infect Microbiol. 2016;6:78. doi: 10.3389/fcimb.2016.00078.
  4. Kogan M.I., Naboka Y.L., Ibishev K.S., Gudima I.A., Naber K.G. Human urine is not sterile - shift of paradigm. Urol Int. 2015;94(4):445-452. doi: 10.1159/000369631.
  5. Santiago-Rodriguez T.M., Ly M., Bonilla N., Pride D.T. The human urine virome in association with urinary tract infections. Front Microbiol. 2015;6:14. doi: 10.3389/fmicb.2015.00014.
  6. Mueller E.R., Wolfe A.J., Brubaker L. Female urinary microbiota. Curr Opin Urol. 2017;27(3):282-286. doi: 10.1097/M0U.0000000000000396.
  7. Santiago-Rodriguez T.M. Identification and Quantification of DNA Viral Populations in Human Urine Using Next Generation Sequencing Approaches. Methods Mol Biol. 2018;1838:191-200. doi: 10.1007/978- 1-4939-8682-8_14.
  8. Siddiqui H., Nederbragt A.J., Lagesen K., Jeansson S.L., Jakobsen K.S. Assessing diversity of the female urine microbiota by high throughput sequencing of 16S rDNA amplicons. BMC Microbiol. 2011;11:244. doi: 10.1186/1471-2180-11-244
  9. Pearce M.M., Hilt E.E., Rosenfeld A.B., Zilliox M.J., Thomas-White K., Fok C., Kliethermes S., Schreckenberger P.C., Brubaker L., Gai X., Wolfe A.J. The female urinary microbiome: a comparison of women with and without urgency urinary incontinence. MBio. 2014;5(4):e01283-14. doi: 10.1128/mBio.01283-14
  10. Nelson D.E., Van Der Pol B., Dong Q., et al. Characteristic male urine microbiomes associate with asymptomatic sexually transmitted infection. PLoS One. 2010;5(11):e14116. doi: 10.1371/journal.pone.0014116
  11. Крахоткин Д.В., Иванов С.Н., Набока Ю.Л., Коган М.И., Гудима И.А., Ильяш А.В., Савкин М.Э., Красулин В.В., Сизякин Д.В. Вирусные патогены при урологических заболеваниях. Медицинский вестник Юга России. 2018;9(4): 14-21. doi: 10.21886/2219-8075-2018-9-414-21
  12. Jhang J.F., Hsu Y.H., Peng C.W., Jiang Y.H., Ho H.C., Kuo H.C.. Epstein-Barr Virus as a Potential Etiology of Persistent Bladder Inflammation in Human Interstitial Cystitis/Bladder Pain Syndrome. J Urol. 2018;200(3):590-596. doi: 10.1016/j.juro.2018.03.133
  13. Ибишев Х.С., Крахоткин Д.В., Васильев А.А., Крайний П.А. Рецидивирующая инфекция нижних мочевых путей вирусной этиологии. Вестник урологии. 2017;5(1):26-31. doi: 10.21886/2308-6424-2017-5-1-26-31
  14. Bradshaw C.S., Tabrizi S.N., Read T.R., Garland S.M., Hopkins C.A., Moss L.M., Fairley C.K. Etiologies of nongonococcal urethritis: bacteria, viruses, and the association with orogenital exposure. J Infect Dis. 2006;193(3):336-345. doi: 10.1086/499434
  15. Гомберг М.А., Винаров А.З., Евдокимов В.В. Герпетическая инфекция в урологической практике. Эффективная фармакотерапия. 2012;43:6-9
  16. Р.С. Козлов, В.В. Меньшиков, В.С. Михайлова, Б.Ф. Шуляк, Т.И. Долгих, А.Н. Круглов, Е.В. Алиева, В.Е. Маликова. Бактериологический анализ мочи: Клинические рекомендации. М., 2014
  17. Организация работы лабораторий, использующих методы амплификации нуклеиновых кислот при работе с материалом, содержащим микроорганизмы I-IV групп патогенности: Методические указания. М.: Федеральный центр гигиены и эпидемиологии Роспотребнадзора, 2010
  18. Abeles S.R., Pride D.T. Molecular bases and role of viruses in the human microbiome. J Mol Biol. 2014;426(23):3892-3906. Doi: 10.1016/j. jmb.2014.07.002.
  19. Duerkop B.A., Hooper L.V. Resident viruses and their interactions with the immune system. Nat Immunol. 2013;14(7):654-659. Doi: 10.1038/ ni.2614.
  20. Hooper L.V., Littman D.R., Macpherson A.J. Interactions between the microbiota and the immune system. Science. 2012;336(6086):1268-1273. doi: 10.1126/science.1223490.
  21. Набока Ю.Л., Коган М.И., Васильева Л.И., Гудима И.А., Мирошниченко Е.А., Ибишев Х.С. Бактериальная микст инфекция у женщин с хроническим рецидивирующим циститом. Журнал микробиологии, эпидемиологии и иммунобиологии. 2011;1:8-12
  22. Siddiqui H., Nederbragt A.J., Lagesen K., Jeansson S.L., Jakobsen K.S. Assessing diversity of the female urine microbiota by high throughput sequencing of 16S rDNA amplicons. BMC Microbiol. 2011;11:244. doi: 10.1186/1471-2180-11-244
  23. Набока Ю.Л., Ильяш А.В., Крахоткин Д.В. Вирусо-бактеральные ассоциации, верифицированные в моче здоровых людей (пилотное исследование). Вестник урологии. 2018;6(3):44-49. doi: 10.21886/2308-6424-2018-6-3-44-49
  24. Набока Ю.Л., Коган М.И., Морданов С.В., Ибишев Х.С., Ильяш А.В., Гудима И.А. Бактериально-вирусная микробиота мочи при неосложнённой рецидивирующей инфекции нижних мочевых путей (пилотное исследование). Вестник урологии. 2019;7(4):13-19. doi: 10.21886/2308-6424-2019-7-4-13-19
  25. Arora N., Novak Z., Fowler K.B., Boppana S.B., Ross S.A. Cytomegalovirus viruria and DNAemia in healthy seropositive women. J Infect Dis. 2010;202(12):1800-1803. doi: 10.1086/657412.
  26. Boukoum H., Nahdi I., Sahtout W., Skiri H., Segondy M., Aouni M. BK and JC virus infections in healthy patients compared to kidney transplant recipients in Tunisia. Microb Pathog. 2016;97:204-208. Doi: 10.1016/j. micpath. 2016.06.015.
  27. Lee S.H., Hong S.H., Lee J.Y., Hwang T.K., Kim K.S., Lee H., Choi Y.J. Asymptomatic hematuria associated with urinary polyomavirus infection in immunocompetent patients. J Med Virol. 2014;86(2):347-353. doi: 10.1002/jmv.23724.
  28. Moustafa A., Li W., Singh H., Moncera K.J., Torralba M.G., Yu Y., Manuel O., Biggs W., Venter J.C., Nelson K.E., Pieper R., Telenti A. Microbial metagenome of urinary tract infection. Sci Rep. 2018;8( 1):4333. doi: 10.1038/s41598-018-22660-8.
  29. Rani A., Ranjan R., McGee H.S., Metwally A., Hajjiri Z., Brennan D.C., Finn P.W., Perkins D.L. A diverse virome in kidney transplant patients contains multiple viral subtypes with distinct polymorphisms. Sci Rep. 2016;6:33327. doi: 10.1038/srep33327
  30. Garretto A., Thomas-White K., Wolfe A.J., Putonti C. Detecting viral genomes in the female urinary microbiome. J Gen Virol. 2018;99(8):1141- 1146. doi: 10.1099/jgv.0.001097.
  31. Varyukhina S., Freitas M., Bardin S., Robillard E., Tavan E, Sapin C., Grill J.P., Trugnan G. Glycan-modifying bacteria-derived soluble factors from Bacteroides thetaiotaomicron and Lactobacillus casei inhibit rotavirus infection in human intestinal cells. Microbes Infect. 2012;14(3):273-278. doi: 10.1016/j.micinf.2011.10.007.
  32. Gounder A.P., Wiens M.E., Wilson S.S., Lu W., Smith J.G. Critical determinants of human a-defensin 5 activity against non-enveloped viruses. J Biol Chem. 2012;287(29):24554-24562. doi: 10.1074/jbc. M112.354068.
  33. Gao W., Weng J., Gao Y., Chen X. Comparison of the vaginal microbiota diversity of women with and without human papillomavirus infection: a cross-sectional study. BMC Infect Dis. 2013;13:271. doi: 10.1186/14712334-13-271.

Supplementary files

Supplementary Files
Action
1. JATS XML

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies