Intestinal microbiota in patients with uncomplicated lower urinary tract infection: an observational case-control study

Cover Page

Cite item

Full Text

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

Abstract

Background. Uncomplicated lower urinary tract infection (ULUTI) is one of the most common infectious and inflammatory diseases and is characterized by a high recurrence rate. It is known that the main source of pathogens is the intestine, where uropathogens exist among a complex microecological community – the intestinal microbiota (IM). To date, there are a limited number of studies on the relationship between ULUTI and IM, and there are no studies of this relationship using the gas chromatography-mass spectrometry (GCMS) method by the microbial marker mass spectrometry (MMMS) technique.

Objective. Assessment of the state of the IM and its impact on the development of the disease in patients with ULUTI.

Methods. An observational case-control study was conducted in the period from 01.08.2021 to 28.02.2023 with the participation of 33 patients with episodes of symptomatic ULUTI (first-time or relapse). The state of the IM was assessed using GCMS by the MSMM method on fecal samples.

Results. In the ULUTI group, a decrease in the number of Eubacterium spp. biomarkers (median (Me)=7.18, interquartile range (IQR) [4.24; 11.98] vs. Me=19.56, IQR [7.21; 26.85] ×109 cells/g; p=0.005), Clostridium propionicum (Me=0.26, IQR [0.05; 0.49] vs. Me=0.76, IQR [0.25; 4.14] ×109 cells/g; p=0.007), Propionibacterium jensenii (Me=4.71, IQR [2.06; 7.65] vs. Me=8.18, IQR [3.67; 15.57] ×109 cells/g; p=0.045), and a higher number of Peptostreptococcus anaerobius 18623 (Me=4.31, IQR [2.29; 6.53] vs. Me=2.07, IQR [0.59; 4.53] ×109 cells/g; p=0.031) compared to the group of healthy volunteers (HV) was noted. No significant differences in the number of Bifidobacterium spp. and Lactobacillus spp. markers were found (p>0.05).

It was determined that the most significant factor in the IM structure that has a protective effect in the context of ULUTI is Eubacterium spp. In the logistic regression model, it was found that an increase in the number of Eubacterium spp. was associated with a lower probability of having the disease (OR=0.885, 95% CI [0.817, 0.959]; p=0.003).

According to GCMS data, the level of Eubacterium spp. below 15.16×109 cells/g in fecal microbiota can be considered as a risk factor for the development of ULUTI (OR=15.95, 95% CI [3.60, 70.54]; p<0.001).

Conclusion. The state of the intestinal microbiota can have a significant impact on the risk of developing ULUTI. Further extensive studies to obtain a more complete picture of the relationship between intestinal microbiota and ULUTI and to develop new therapeutic approaches to disease prevention are required.

Full Text

Restricted Access

About the authors

N. V. Sturov

Peoples’ Friendship University of Russia

Email: sturov_nv@rudn.ru
ORCID iD: 0000-0002-3138-8410

Cand. Sci. (Med.), Associate Professor, Head of the Department of General Medical Practice, Medical Institute

Russian Federation, Moscow

Sergey V. Popov

Peoples’ Friendship University of Russia

Author for correspondence.
Email: popov_serv@pfur.ru
ORCID iD: 0000-0002-0567-4616

Dr. Sci. (Med.), Professor, Department of General Medical Practice, Medical Institute

Russian Federation, Moscow

V. A. Zhukov

Peoples’ Friendship University of Russia

Email: zhukov_vlan@rudn.ru
ORCID iD: 0000-0001-9995-264X

Cand. Sci. (Med.), Associate Professor, Department of General Medical Practice, Medical Institute

Russian Federation, Moscow

T. V. Lyapunova

Peoples’ Friendship University of Russia

Email: lyapunova_tv@rudn.ru
ORCID iD: 0000-0002-1141-0764

Cand. Sci. (Med.), Associate Professor, Department of Medical Informatics and Telemedicine

Russian Federation, Moscow

I. V. Zelensky

Peoples’ Friendship University of Russia

Email: zelenskiy_iv@pfur.ru
ORCID iD: 0009-0004-9603-0067

Laboratory Assistant, Department of General Medical Practice, Medical Institute

Russian Federation, Moscow

References

  1. Duane S., Beecher C., Vellinga A., et al. A systematic review of the outcomes reported in the treatment of uncomplicated urinary tract infection clinical trials. JAC Antimicrob Resist. 2022;4(2):dlac025. doi: 10.1093/jacamr/dlac025.
  2. Сурсякова К.И., Сафьянова Т.В. Некоторые эпидемиологические особенности инфекций мочевыводящих путей (обзор литературы). Сибирский научный медицинский журнал. 2017;37(6):61–70. [Sursyakova K.I., Safyanova T.V. Some epidemiological features of urinary tract infections (review). Sibirskij Nauchnyj Medicinskij Zhurnal. 2017;37(6):61–70. (In Russ.)].
  3. Цистит у женщин. Клинические рекомендации Министерства здравоохранения РФ. М., 2024. 40 с. [Cystitis in women. Clinical guidelines of the Ministry of Health of the Russian Federation. M., 2024. 40 p. (In Russ.)].
  4. Синякова Л.А., Косова И.В., Лоран О.Б., Барсегян В.А. Пособие для врачей-терапевтов по острому циститу (неосложненная инфекция мочевых путей) (код по МКБ-10 N30.0). Фарматека. 2024;31(1):198–207. doi: 10.18565/pharmateca.2024.1.198-206. [Sinyakova L.A., Kosova I.V., Loran O.B., Barsegian V.A. Guideline on acute cystitis (uncomplicated urinary tract infection) (ICD-10 code N30.0) for general practitioners. Farmateka. 2024;31(1):198–207. doi: 10.18565/pharmateca.2024.1.198-206. (In Russ.)].
  5. Антимикробная терапия и профилактика инфекций почек, мочевыводящих путей и мужских половых органов. Федеральные клинические рекомендации. Под ред. Аляева Ю.Г., Аполихина О.И., Пушкаря Д.Ю., Козлова Р.С., Камалова А.А., Перепановой Т.С. М.: Уромедиа, 2022. 126 с. [Antimicrobial therapy and prevention of kidney, urinary tract and male genital tract infections. Federal clinical guidelines. Edited by Alayev Yu.G., Apolikhin O.I., Pushkar D.Yu., Kozlov R.S., Kamalov A.A., Perepanova T.S. Moscow: Uromedia, 2022. 126 p. (In Russ.)].
  6. Czajkowski K., Bros-Konopielko M., Teliga-Czajkowska J. Urinary tract infection in women. Prz Menopauzalny. 2021;20(1):40–47. doi: 10.5114/pm.2021.105382.
  7. Suskind A.M., Saigal C.S., Hanley J.M., et al. Incidence and Management of Uncomplicated Recurrent Urinary Tract Infections in a National Sample of Women in the United States. Urology. 2016;90:50–55. doi: 10.1016/j.urology.2015.11.051.
  8. Medina M., Castillo-Pino E. An introduction to the epidemiology and burden of urinary tract infections. Ther Adv Urol. 2019;11:1756287219832172. doi: 10.1177/1756287219832172.
  9. Iqbal Z.S., Halkjær S.I., Ghathian K.S.A., et al. The Role of the Gut Microbiome in Urinary Tract Infections: A Narrative Review. Nutrients. 2024;16(21):3615. doi: 10.3390/nu16213615.
  10. Палагин И.С., Сухорукова М.В., Дехнич А.В. и др. Антибиотикорезистентность возбудителей внебольничных инфекций мочевых путей в России: результаты многоцентрового исследования «ДАРМИС-2018». Клиническая микробиология и антимикробная химиотерапия. 2019; 21(2):134–146. doi: 10.36488/cmac.2019.2.134–146. [Palagin I.S., Sukhorukova M.V., Dekhnich A.V. et al. Antimicrobial resistance of pathogens causing community-acquired urinary tract infections in Russia: results of the multicenter study “DARMIS-2018”. Kliniceskaa Mikrobiologia i Antimikrobnaa Himioterapia. 2019;21(2):134–146. doi: 10.36488/cmac.2019.2.134-146. (In Russ.)].
  11. Kulchenko N.G., Kostin A.A., Yatsenko E.V. Аntimicrobial therapy of acute uncomplicated cystitis with nifuratel. Archiv EuroMedica. 2019;9(3):71–73. doi: 10.35630/2199-885X/2019/9/3.22.
  12. Yamamoto S., Tsukamoto T., Terai A., et al. Genetic evidence supporting the fecal-perineal-urethral hypothesis in cystitis caused by Escherichia coli. J Urol. 1997;157(3):1127–1129.
  13. Nielsen K.L., Dynesen P., Larsen P., Frimodt-Møller N. Faecal Escherichia coli from patients with E. coli urinary tract infection and healthy controls who have never had a urinary tract infection. J Med Microbiol. 2014;63(Pt 4):582–589. doi: 10.1099/jmm.0.068783-0.
  14. Salazar A.M., Neugent M.L., De Nisco N.J., Mysorekar I.U. Gut-bladder axis enters the stage: Implication for recurrent urinary tract infections. Cell Host Microbe. 2022;30(8):1066–1069. doi: 10.1016/j.chom.2022.07.008.
  15. Tchesnokova V.L., Rechkina E., Chan D., et al. Pandemic Uropathogenic Fluoroquinolone-resistant Escherichia coli Have Enhanced Ability to Persist in the Gut and Cause Bacteriuria in Healthy Women. Clin Infect Dis. 2020;70(5):937–939. doi: 10.1093/cid/ciz547.
  16. Conway T., Cohen P.S. Commensal and Pathogenic Escherichia coli Metabolism in the Gut. Microbiol Spectr. 2015;3(3). doi: 10.1128/microbiolspec.MBP-0006-2014.
  17. Magruder M., Sholi A.N., Gong C., et al. Gut uropathogen abundance is a risk factor for development of bacteriuria and urinary tract infection. Nat Commun. 2019;10(1):5521. doi: 10.1038/s41467-019-13467-w.
  18. Pigrau C., Escola-Verge L. Recurrent urinary tract infections: from pathogenesis to prevention. Med Clin (Barc). 2020;155(4):171–177. doi: 10.1016/j.medcli.2020.04.026.
  19. Anger J., Lee U., Ackerman A.L., et al. Recurrent Uncomplicated Urinary Tract Infections in Women: AUA/CUA/SUFU Guideline. J Urol. 2019;202(2):282–289. doi: 10.1097/JU.0000000000000296.
  20. Thänert R., Reske K.A., Hink T., et al. Comparative Genomics of Antibiotic-Resistant Uropathogens Implicates Three Routes for Recurrence of Urinary Tract Infections. mBio. 2019;10(4):e01977-19. doi: 10.1128/mBio.01977-19.
  21. Forde B.M., Roberts L.W., Phan M.D., et al. Population dynamics of an Escherichia coli ST131 lineage during recurrent urinary tract infection. Nat Commun. 2019;10(1):3643. doi: 10.1038/s41467-019-11571-5.
  22. Perez N.B., Dorsen C., Squires A. Dysbiosis of the Gut Microbiome: A Concept Analysis. J Holist Nurs. 2020;38(2):223–232. doi: 10.1177/0898010119879527.
  23. Alagiakrishnan K., Morgadinho J., Halverson T. Approach to the diagnosis and management of dysbiosis. Front Nutr. 2024;11:1330903. doi: 10.3389/fnut.2024.1330903.
  24. Методические рекомендации МР 2.3.1.0253-21 «Нормы физиологических потребностей в энергии и пищевых веществах для различных групп населения Российской Федерации». [Methodological recommendations MR 2.3.1.0253-21 «Norms of physiological needs for energy and nutrients for various population groups of the Russian Federation».(In Russ.)].
  25. Hooks K.B., O’Malley M.A. Dysbiosis and Its Discontents. mBio. 2017;8(5):e01492-17. doi: 10.1128/mBio.01492-17.
  26. Magruder M., Edusei E., Zhang L., et al. Gut commensal microbiota and decreased risk for Enterobacteriaceae bacteriuria and urinary tract infection. Gut Microbes. 2020;12(1):1805281. doi: 10.1080/19490976.2020.1805281.
  27. Worby CJ, Schreiber HL, Straub TJ, et al. Longitudinal multi-omics analyses link gut microbiome dysbiosis with recurrent urinary tract infections in women. Nat Microbiol. 2022;7(5):630-639. doi: 10.1038/s41564-022-01107-x.
  28. Rizal N.S.M., Neoh H. min, Ramli R., et al. Advantages and Limitations of 16S rRNA Next-Generation Sequencing for Pathogen Identification in the Diagnostic Microbiology Laboratory: Perspectives from a Middle-Income Country. Diagnostics. 2020;10(10):816. doi: 10.3390/diagnostics10100816.
  29. Bailen M., Bressa C., Larrosa M., Gonzalez-Soltero R. Bioinformatic strategies to address limitations of 16rRNA short-read amplicons from different sequencing platforms. J Microbiol Methods. 2020;169:105811. doi: 10.1016/j.mimet.2019.105811.
  30. Regueira-Iglesias A., Balsa-Castro C., Blanco-Pintos T., Tomas I. Critical review of 16S rRNA gene sequencing workflow in microbiome studies: From primer selection to advanced data analysis. doi: 10.1111/omi.12434.
  31. Elie C., Perret M., Hage H., et al. Comparison of DNA extraction methods for 16S rRNA gene sequencing in the analysis of the human gut microbiome. Sci Rep. 2023;13(1):10279. doi: 10.1038/s41598-023-33959-6.
  32. Delaney C., Veena C.L.R., Butcher M.C., et al. Limitations of using 16S rRNA microbiome sequencing to predict oral squamous cell carcinoma. APMIS. 2023 Jun;131(6):262–276. doi: 10.1111/apm.13315.
  33. O’Callaghan J.L., Willner D., Buttini M., et al. Limitations of 16S rRNA Gene Sequencing to Characterize Lactobacillus Species in the Upper Genital Tract. Front Cell Dev Biol. 2021;9. doi: 10.3389/fcell.2021.641921.
  34. Teng F., Darveekaran Nair S.S., Zhu P., et al. Impact of DNA extraction method and targeted 16S-rRNA hypervariable region on oral microbiota profiling. Sci Rep. 2018;8(1):16321. doi: 10.1038/s41598-018-34294-x.
  35. Regueira-Iglesias A., Vazquez-Gonzalez L., Balsa-Castro C., et al. Impact of 16S rRNA Gene Redundancy and Primer Pair Selection on the Quantification and Classification of Oral Microbiota in Next-Generation Sequencing. Microbiol Spectr. 2023;11(2):e0439822. doi: 10.1128/spectrum.04398-22.
  36. Осипов Г.А., Парфенов А.И., Верховцева Н.В. и др. Количественный in situ анализ микробиоты кишечной стенки и фекалий методом газовой хроматографии – масс-спектрометрии. Клиническая лабораторная диагностика. 2004;(9):67c-68. [Osipov G.A., Parfenov A.I., Verkhovtseva N.V., et al. Quantitative in situ analysis of the microbiota of the intestinal wall and feces using gas chromatography – mass spectrometry. Klinichescheskaya Laboratornaya Diagnostika. 2004;(9):67c-68. (In Russ.)].
  37. Платонова А.Г., Осипов Г.А., Бойко Н.Б. и др. Хромато-масс-спектрометрическое исследование микробных жирных кислот в биологических жидкостях человека и их клиническая значимость. Клиническая лабораторная диагностика. 2015;60(12):46–55. [Platonova A.G., Osipov G.A., Boyko N.B., et al. Chromato-mass spectrometric study of microbial fatty acids in human biological fluids and their clinical significance. Klinichescheskaya Laboratornaya Diagnostika. 2015;60(12):46–55. (In Russ.)].
  38. Осипов Г.А., Родионов Г.Г. Применение метода масс-спектрометрии микробных маркеров в клинической практике. Поликлиника. 2013;(1-3):68–73. [Osipov G.A., Rodionov G.G. Application of the method of mass spectrometry of microbial markers in clinical practice. Poliklinika. 2013;(1-3):68–73. (In Russ.)].
  39. Осипов Г.А., Зыбина Н.Н., Родионов Г.Г. Опыт применения масс-спектрометрии микробных маркеров в лабораторной диагностике. Медицинский Алфавит. 2013;1(3):64–67. [Osipov G.A., Zybina N.N., Rodionov G.G. Experience in using mass spectrometry of microbial markers in laboratory diagnostics. Medical alphabet. 2013;1(3):64–67. (In Russ.)].
  40. Набока Ю.Л., Гудима И.А., Джалагония К.Т. и др. Микробиота мочи и толстого кишечника у женщин с рецидивирующем неосложненной инфекцией нижних мочевых путей. Вестник урологии. 2019;7(2):59–65. doi: 10.21886/2308-6424-2019-7-2-59-65. [Naboka Yu.L., Gudima I.A., Dzhalagoniya K.T., et al. Urine and colon microbiota in patients with recurrent uncomplicated lower urinary tract infection. Urology Herald. 2019;7(2):59–65. doi: 10.21886/2308-6424-2019-7-2-59-65. (In Russ.)].
  41. Choi J, Thanert R, Reske KA, et al. Gut microbiome correlates of recurrent urinary tract infection: a longitudinal, multi-center study. eClinicalMedicine. 2024;71. doi: 10.1016/j.eclinm.2024.102490.
  42. Miller SJ, Carpenter L, Taylor SL, et al. Intestinal microbiology and urinary tract infection associated risk in long-term aged care residents. Commun Med. 2024;4(1):1–10. doi: 10.1038/s43856-024-00583-y.
  43. Legaria M.C., Nastro M., Camporro J., et al. Peptostreptococcus anaerobius: Pathogenicity, identification, and antimicrobial susceptibility. Review of monobacterial infections and addition of a case of urinary tract infection directly identified from a urine sample by MALDI-TOF MS. Anaerobe. 2021;72:102461. doi: 10.1016/j.anaerobe.2021.102461.
  44. Леванова Л.А., Марковская А.А., Отдушкина Л.Ю., Захарова Ю.В. Роль кишечной микробиоты в развитии инфекций мочевыводящих путей у детей. Фундаментальная и клиническая медицина. 2021;6(2):24–30. doi: 10.23946/2500-0764-2021-6-2-24-30. [Levanova L.A., Markovskaya A.A., Otdushkina L.Yu., Zakharova Yu.V. Gut microbiota and urinary tract infections in children. Fundamental and Clinical Medicine. 2021;6(2):24–30. doi: 10.23946/2500-0764-2021-6-2-24-30 (In Russ.)].
  45. Timm M.R., Russell S.K., Hultgren S.J. Urinary tract infections: pathogenesis, host susceptibility and emerging therapeutics. Nat Rev Microbiol. Published online September 9, 2024:1–15. doi: 10.1038/s41579-024-01092-4.
  46. Klein R.D., Hultgren S.J. Urinary tract infections: microbial pathogenesis, host-pathogen interactions and new treatment strategies. Nat Rev Microbiol. 2020;18(4):211–226. doi: 10.1038/s41579-020-0324-0.
  47. Sun M., Wu W., Chen L., et al. Microbiota-derived short-chain fatty acids promote Th1 cell IL-10 production to maintain intestinal homeostasis. Nat Commun. 2018;9(1):3555. doi: 10.1038/s41467-018-05901-2.
  48. Goncalves P., Araujo J.R., Di Santo J.P. A Cross-Talk Between Microbiota-Derived Short-Chain Fatty Acids and the Host Mucosal Immune System Regulates Intestinal Homeostasis and Inflammatory Bowel Disease. Inflamm Bowel Dis. 2018;24(3):558–572. doi: 10.1093/ibd/izx029.
  49. Shimizu J., Kubota T., Takada E., et al. Propionate-producing bacteria in the intestine may associate with skewed responses of IL10-producing regulatory T cells in patients with relapsing polychondritis. PLOS ONE. 2018;13(9):e0203657. doi: 10.1371/journal.pone.0203657.
  50. Mukherjee A., Lordan C., Ross R.P., Cotter P.D. Gut microbes from the phylogenetically diverse genus Eubacterium and their various contributions to gut health. Gut Microbes. 2020;12(1):1802866. doi: 10.1080/19490976.2020.1802866.
  51. Zhang S., Dogan B., Guo C., et al. Short Chain Fatty Acids Modulate the Growth and Virulence of Pathosymbiont Escherichia coli and Host Response. Antibiotics (Basel). 2020;9(8):462. doi: 10.3390/antibiotics9080462.

Supplementary files

Supplementary Files
Action
1. JATS XML
2. Fig. 1. Statistically significant differences in the number of bacterial markers between the NINMP and ZD groups

Download (95KB)
3. Fig. 2. Spearman correlation heat maps

Download (1MB)
4. Fig. 2

Download (1MB)
5. Fig. 3. LASSO regression for 11 and 4 predictors of NINMP development

Download (226KB)
6. Fig. 4. ROC curve for the predictor Eubacterium spp.

Download (54KB)
7. Fig. 5. Frequency of occurrence of Eubacterium spp. <15.16x10⁹ cells/g

Download (42KB)

Copyright (c) 2025 Bionika Media