Urine microbiota and bladder cancer

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription Access

Abstract

Urine analysis data obtained using modern microbiological methods and 16S rRNA gene sequencing technology indicate that the urinary system has its own microbial ecosystem. Individual microbiota members can play a key role in the development of cancer. Certain bacterial taxa have been revealed in bladder urothelial carcinoma cells that can affect carcinogenesis, treatment response, and the development of relapses through various mechanisms. The studies are conducted to use not only vaccine strains, but also probiotic strains and oncolytic bacteria for the treatment and prevention of relapses.

About the authors

Igor Yu. Lisitsyn

Granov Russian Research Center of Radiology and Surgical Technologies

Author for correspondence.
Email: urologlis@mail.ru

MD, Cand. Sci. (Medicine)

Russian Federation, Saint Petersburg

Dmitrii N. Maistrenko

Granov Russian Research Center of Radiology and Surgical Technologies

Email: may64@inbox.ru
ORCID iD: 0000-0001-8174-7461
SPIN-code: 7363-4840

MD, Dr. Sci. (Medicine)

Russian Federation, Saint Petersburg

Dmitrii A. Granov

Granov Russian Research Center of Radiology and Surgical Technologies

Email: da_granov@rrcrst.ru
ORCID iD: 0000-0002-8746-8452
SPIN-code: 5256-2744

MD, Dr. Sci. (Medicine), Professor, Academician of the Russian Academy of Sciences

Russian Federation, Saint Petersburg

Svetlana Yu. Rumyantseva

Granov Russian Research Center of Radiology and Surgical Technologies

Email: si_rumiantseva@rrcrst.ru

MD, Cand. Sci. (Medicine)

Russian Federation, Saint Petersburg

Oleg E. Molchanov

Granov Russian Research Center of Radiology and Surgical Technologies

Email: molchanovo@mail.ru
ORCID iD: 0000-0003-3882-1720
SPIN-code: 5557-6484

MD, Dr. Sci. (Medicine)

Russian Federation, Saint Petersburg

Olga E. Punchenko

North-Western State Medical University named after I.I. Mechnikov; Institute of Experimental Medicine

Email: olga.punchenko@szgmu.ru
ORCID iD: 0000-0002-1847-3231
SPIN-code: 5029-7130

MD, Cand. Sci. (Medicine)

Russian Federation, Saint Petersburg; Saint Petersburg

References

  1. Axel EM, Matveev VВ. Statistics of malignant tumors of urinary and male urogenital organs in Russia and the countries of the former USSR. Cancer Urology. 2019;15(2):15–24. EDN: VMMGKE doi: 10.17650/1726-9776-2019-15-2-15-24
  2. Popov SV, Guseynov RG, Khizha VV, et al. Main epidemiological data on cases of malignant neoplasms of the bladder in Saint Petersburg in 2012–2021. Cancer Urology. 2023;19(2):133–145. EDN: VMMGKE doi: 10.17650/1726-9776-2023-19-2-133-145
  3. Zhang W, Yang F, Mao S, et al. Bladder cancer-associated microbiota: Recent advances and future perspectives. Heliyon. 2023;9(1):el.3012. doi: 10.1016/j.heliyon.2023.e13012
  4. Sapozhkova JY, Makolin IA. Malignant neoplasms of urogenital system in men. In: Medicine: education, practice and science: a collection of scientific papers. Vol. 1. Moscow: Medicine; 2018. P. 11–16. EDN: XSYVTV (In Russ.)
  5. Hrbáček J, Tláskal V, Čermák P, et al. Bladder cancer is associated with decreased urinary microbiota diversity and alterations in microbial community composition. Urol Oncol: Semin Orig Investig. 2023;41(2):107.e15–107.e22. doi: 10.1016/j.urolonc.2022.09.018
  6. Yacouba A, Alou MT, Lagier JC, et al. Urinary microbiota and bladder cancer: A systematic review and a focus on uropathogens. Semin Cancer Biol. 2022;86(3):875–884. doi: 10.1016/j.semcancer.2021.12.010
  7. Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209–249. doi: 10.3322/caac.21660
  8. Kogan MI, Naboka YuL, Ryzhkin AV, Vasilyev ON. Microbiota/microbiome urine and bladder cancer. Cancer Urology. 2020;16(2): 97–103. EDN: FZBZCA doi: 10.17650/1726-9776-2020-16-2-97-103
  9. Jubber I, Ong S, Bukavina L, et al. Epidemiology of bladder cancer in 2023: a systematic review of risk factors. Eur Urol. 2023;84(2): 176–190. doi: 10.1016/j.eururo.2023.03.029
  10. Gaffney CD, Katims A, D’Souza N, et al. Bladder cancer carcinogens: Opportunities for risk reduction. Eur Urol Focus. 2023;9(4): 575–578. doi: 10.1016/j.euf.2023.03.017
  11. Dubrovin VN. Epidemiology of bladder cancer. Kazan medical journal. 1996;77(4):294–298. doi: 10.17816/kazmj104542
  12. Shaposhnikov AV, Kit OI, Dzhenkova EA, Legostaeva KV. Cancer–induced diagnostic and therapeutic interventions. Siberian journal of oncology. 2021;20(4):146–151. EDN: VGEFDT doi: 10.21294/1814-4861-2021-20-4-146-151
  13. He C, Lei B, Huang L, et al. Gut microbial composition changes in bladder cancer patients: a case-control study in Harbin, China. Asia Pac J Clin Nutr. 2020;29(2):395–403. doi: 10.6133/apjcn.202007_29(2).0022
  14. Ma W, Zhang W, Shen L, et al. Can smoking cause differences in urine microbiome in male patients with bladder cancer? A retrospective study. Front Oncol. 2021;11:677605. doi: 10.3389/fonc.2021.677605
  15. Allen MJ, Boyland E, Dukes CE, et al. Cancer of the urinary bladder induced in mice with metabolites of aromatic amines and tryptophan. Br J Cancer. 1957;11(2):212–228. doi: 10.1038/bjc.1957.29
  16. Talaska G. Aromatic amines and human urinary bladder cancer: exposure sources and epidemiology. J Environ Sci Health C. 2003;21(1):29–43. doi: 10.1081/GNC-120021372
  17. Freudenthal RI, Stephens E, Anderson DP. Determining the potential of aromatic amines to induce cancer of the urinary bladder. Int J Toxicol. 1999;18(5):353–359. doi: 10.1080/1091581992252
  18. Gizinger OA, Radzinskiy VE. Human papillomavirus: pathogenesis and correction of immune disturbances. Doctor.Ru. 2021;20(6):80–86. EDN: WQGJLJ doi: 10.31550/1727-2378-2021-20-6-80-86
  19. Krakhotkin DV, Ivanov SN, Naboka YL, et al. Viral pathogens in urological diseases. Medical Herald of the South of Russia. 2018;9(4): 14–21. EDN: YVDGBV doi: 10.21886/2219-8075-2018-9-4-14-21
  20. Omarova KG, Aleshina NI, Ponezhevа ZB, et al. Risks of oncologic pathology in parasitosis at the present time. Therapeutic archive. 2020;92(11):82–85. EDN: MNEOFR doi: 10.26442/00403660.2020.11.000710
  21. Zorov DB, Plotnikov EY, Silachev DN, et al. Microbiota and mitobiota. Putting an equal sign between mitochondria and bacteria. Biochemistry (Moscow). 2014;79(10):1252–1268. EDN: TLTRRV doi: 10.1134/S0006297914100046
  22. Zeng J, Zhang G, Chen C, et al. Alterations in urobiome in patients with bladder cancer and implications for clinical outcome: a single-institution study. Front Cell Infect Microbiol. 2020;10:555508. doi: 10.3389/fcimb.2020.555508
  23. Adebayo AS, Suryavanshi MV, Bhute S, et al. The microbiome in urogenital schistosomiasis and induced bladder pathologies. PLoS Neglected Trop Dis. 2017;11(11):e0005826. doi: 10.1371/journal.pntd.0005826
  24. Wolfe AJ, Brubaker L. “Sterile urine” and the presence of bacteria. Eur Urol. 2015;68(2):173–174. doi: 10.1016/j.eururo.2015.02.041
  25. Brubaker L, Wolfe AJ. The female urinary microbiota, urinary health and common urinary disorders. Ann Transl Med. 2017;5(2):34. doi: 10.21037/atm.2016.11.62
  26. Bi H, Tian Y, Song C, et al. Urinary microbiota — a potential biomarker and therapeutic target for bladder cancer. J Med Microbiol. 2019;68(10):1471–1478. doi: 10.1099/jmm.0.001058
  27. Mansour B, Monyók А, Makra N, et al. Bladder cancer-related microbiota: Examining differences in urine and tissue samples. Sci Rep. 2020;10(1):11042. doi: 10.1038/s41598-020-67443-2
  28. Lotte R, Lotte L, Ruimy R. Actinotignum schaalii (formerly Actinobaculum schaalii): a newly recognized pathogen-review of the literature. Clin Microbiol Infect. 2016;22(1):28–36. doi: 10.1016/j.cmi.2015.10.038
  29. Brahimi S, Cadoret F, Fournier P-E, et al. ‘Actinotignum timonense’ sp. nov., a new bacterial species isolated from a human urine sample. New Microbes New Infect. 2017;16:47–48. doi: 10.1016/j.nmni.2017.01.002
  30. Zaharova IN, Mumladze EB, Machneva EB, Kasyanova AN. Mechanisms of urinary tract infections and asymptomatic bacteriuria. Pediatrics (Consilium Medicum Supplement). 2018;(1):106–110. EDN: YWOSCR doi: 10.26442/2413-8460_2018.1.106-110
  31. Rocha J, Botelho J, Ksiezarek M, et al. Lactobacillus mulieris sp. nov., a new species of Lactobacillus delbrueckii group. Int J Syst Evol Microbiol. 2020;70(3):1522–1527. doi: 10.1099/ijsem.0.003901
  32. Lewis DA, Brown R, Williams J, et al. The human urinary microbiome; bacterial DNA in voided urine of asymptomatic adults. Front Cell Infect Microbiol. 2013;3:41. doi: 10.3389/fcimb.2013.00041
  33. Peng Z, Zhuang J, Shen B. The role of microbiota in tumorigenesis, progression and treatment of bladder cancer. Microbiome Res Rep. 2024;3:5. doi: 10.20517/mrr.2023.47
  34. Wu P, Zhang G, Zhao J, et al. Corrigendum: profiling the urinary microbiota in male patients with bladder cancer in China. Front Cell Infect Microbiol. 2018;8:429. doi: 10.3389/fcimb.2018.00429
  35. Hussein AA, Elsayed AS, Durrani M, et al. Investigating the association between the urinary microbiome and bladder cancer: An exploratory study. Urol Oncol. 2021;39(6):370.e9–370.e19. doi: 10.1016/j.urolonc.2020.12.011
  36. Parra-Grande M, Ore-Arce M, Martinez-Priego L, et al. Profiling the bladder microbiota in patients with bladder cancer. Front Microbiol. 2022;12:718776. doi: 10.3389/fmicb.2021.718776
  37. Qiu Y, Gao Y, Chen C, et al. Deciphering the influence of urinary microbiota on FoxP3+ regulatory T cell infiltration and prognosis in Chinese patients with non-muscle-invasive bladder cancer. Hum Cell. 2022;35(2):511–521. doi: 10.1007/s13577-021-00659-0
  38. Chipollini J, Wright JR, Nwanosike H, et al. Characterization of urinary microbiome in patients with bladder cancer: results from a single-institution, feasibility study. Urol Oncol. 2020;38(7):615–621. doi: 10.1016/j.urolonc.2020.04.014
  39. Moynihan M, Sullivan T, Provenzano K, Rieger-Christ K. Urinary microbiome evaluation in patients presenting with hematuria with a focus on exposure to tobacco smoke. Res Rep Urol. 2019;11: 359–367. doi: 10.2147/RRU.S233386
  40. Hourigan SK, Zhu W, Wong SWW, et al. Studying the urine microbiome in superficial bladder cancer: samples obtained by midstream voiding versus cystoscopy. BMC Urol. 2020;20:5. doi: 10.1186/s12894-020-0576-z
  41. Liu F, Liu A, Zhang Z, et al. Dysbiosis signatures of the microbial profile in tissue from bladder cancer. Cancer Med. 2019;8(16): 6904–6914. doi: 10.1002/cam4.2419
  42. Mai G, Chen L, Li R, et al. Common core bacterial biomarkers of bladder cancer based on multiple datasets. BioMed Res Int. 2019;2019:4824909. doi: 10.1155/2019/4824909
  43. Hrbacek J, Morais D, Cermak P, et al. Alpha-diversity and microbial community structure of the male urinary microbiota depend on urine sampling method. Sci Rep. 2021;11(1):23758. doi: 10.1038/s41598-021-03292-x
  44. Oresta B, Braga D, Lazzeri M, et al. The microbiome of catheter collected urine in males with bladder cancer according to disease stage. J Urol. 2021;205(1):86–93. doi: 10.1097/JU.0000000000001336
  45. Bučević Popović V, Šitum M, Chow C-ET, et al. The urinary microbiome associated with bladder cancer. Sci Rep. 2018;8(1):12157. doi: 10.1038/s41598-018-29054-w
  46. 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. doi: 10.1016/j.euo.2020.04.002
  47. Vermeulen SH, Hanum N, Grotenhuis AJ, et al. Recurrent urinary tract infection and risk of bladder cancer in the Nijmegen bladder cancer study. Br J Cancer. 2015;112(3):594–600. doi: 10.1038/bjc.2014.601
  48. Pozdeyev ОС. Molecular genetic foundations of pathogenicity of enterobacterium. Practical medicine. 2010;(2):84–88. EDN: MDXIKX
  49. Hannan TJ, Mysorekar IU, Hung CS, et al. Early severe inflammatory responses to uropathogenic E. coli predispose to chronic and recurrent urinary tract infection. PLoS pathogens. 2010;6(8):e1001042. doi: 10.1371/journal.ppat.1001042
  50. Alon-Maimon T, Mandelboim O, Bachrach G. Fusobacterium nucleatum and cancer. Periodontology. 2022;89(1):166–180. doi: 10.1111/prd.12426
  51. Vecherkovskaya MF, Tetz GV, Tetz VV. Microbiota and cancer (review of literature). The Scientific Notes of the Pavlov University. 2020;27(4): 14–27. EDN: CNCWAM doi: 10.24884/1607-4181-2020-27-4-14-27
  52. Miller SI, Ernst RK, Bader MW. LPS, TLR4 and infectious disease diversity. Nat Rev Microbiol. 2005;3(1):36–46. doi: 10.1038/nrmicro1068
  53. Kostin RK, Malyugin DA, Solenova LG, Kulaeva ED. Gut microbiota and carcinogenesis in various human organs. Journal of microbiology, epidemiology and immunobiology. 2023;100(1):110–125. EDN: CYBYBS doi: 10.36233/0372-9311-310
  54. Ding X, Hu W, Li J, et al. Relationship of urinary pathogenic bacteria and stone composition in patients with infectious stones. Chinese J Urol. 2002;(12):734–738.
  55. Wernke KM, Xue M, Tirla A, et al. Structure and bioactivity of colibactin. Bioorg Med Chem Lett. 2020;30(15):127280. doi: 10.1016/j.bmcl.2020.127280
  56. Voloshko LN, Pinevich AV. Diversity of the cyanobacterial toxins. Astrakhan Bulletin for Environmental Education. 2014;(1):68–80. EDN: RXBFSP
  57. Naka T, Fujiwara N, Yano I, et al. Structural analysis of sphingophospholipids derived from Sphingobacterium spiritivorum, the type species of genus Sphingobacterium. Biochim Biophys Acta Mol Cell Biol Lipids. 2003;1635(2–3):83–92. doi: 10.1016/j.bbalip.2003.10.010
  58. Huycke MM, Abrams V, Moore DR. Enterococcus faecalis produces extracellular superoxide and hydrogen peroxide that damages colonic epithelial cell DNA. Carcinogenesis. 2002;23(3):529–536. doi: 10.1093/carcin/23.3.529
  59. Galyamina MA, Pobeguts OV, Gorbachev AYu. The role of mycoplasmas as an infectious agent in carcinogenesis. Advances in Molecular Oncology. 2023;10(3):36–49. EDN: KFGBLE doi: 10.17650/2313-805X-2023-10-3-36-49
  60. Zarei O, Rezania S, Mousavi A. Mycoplasma genitalium and cancer: a brief review. Asian Pac J Cancer Prev. 2013;14(6):3425–3428. doi: 10.7314/APJCP.2013.14.6.3425
  61. Zinatizadeh MR, Masoumalinejad Z, Parnak F. The prevalence of Mycoplasma hyorhinis contamination in tissues samples from cancer patients: A brief report. Mod Med Lab J. 2019;2(1):91–95. doi: 10.30699/mmlj17.1.3.91
  62. Yacoub E, Saed Abdul-Wahab OM, Al-Shyarba MH, Ben Abdelmoumen Mardassi B. The relationship between mycoplasmas and cancer: Is it fact or fiction? Narrative review and update on the situation. J Oncol. 2021;2021:9986550. doi: 10.1155/2021/9986550
  63. Urbanek C, Goodison S, Chang M, et al. Detection of antibodies directed at M. hyorhinis p37 in the serum of men with newly diagnosed prostate cancer. BMC Cancer. 2011;11:233. doi: 10.1186/1471-2407-11-233
  64. Rogers MB. Mycoplasma and cancer: in search of the link. Oncotarget. 2011;2(4):271. doi: 10.18632/oncotarget.264
  65. Lee SH, Mahendran R, Tham SM, et al. Tryptophan–kynurenine ratio as a biomarker of bladder cancer. BJU Int. 2021;127(4):445–453. doi: 10.1111/bju.15205
  66. Chung K-T, Gadupudi GS. Possible roles of excess tryptophan metabolites in cancer. Environ Mol Mutagen. 2011;52(2):81–104. doi: 10.1002/em.20588
  67. Brausi M, Oddens J, Sylvester R, et al. Side effects of Bacillus Calmette-Guérin (BCG) in the treatment of intermediate- and highrisk Ta, T1 papillary carcinoma of the bladder: results of the EORTC genito-urinary cancers group randomised phase 3 study comparing one-third dose with full dose and 1 year with 3 years of maintenance BCG. Eur Urol. 2014;65(1):69–76. doi: 10.1016/j.eururo.2013.07.021
  68. Figurin KM. Intravesical bcg therapy for non-muscle invasive bladder cancer. Cancer Urology. 2012;8(1):14–23. EDN: OTORPF doi: 10.17650/1726-9776-2012-8-1-14-22
  69. Green DB, Kawashima A, Menias CO, et al. Complications of intravesical BCG immunotherapy for bladder cancer. Radiographics. 2019;39(1):80–94. doi: 10.1148/rg.2019180014
  70. Koch GE, Smelser WW, Chang SS. Side effects of intravesical BCG and chemotherapy for bladder cancer: what they are and how to manage them. Urology. 2021;149:11–20. doi: 10.1016/j.urology.2020.10.039
  71. Eissa AS, Rasslan O, Fouad L, et al. Nucleotide oligomerization domain-like receptor 4 (NLR4) gene expression and interleukin 1-β (IL1-β) level in urine samples before and after intravesical BCG therapy for treatment of bladder cancer. Medical Immunology (Russia). 2020;22(6):1141–1154. EDN: UHQQIO doi: 10.15789/1563-0625-NOD-2101
  72. Woolbright BL, Xuan H, Ahmed I, et al. Aging induces changes in cancer formation and microbial content in a murine model of bladder cancer. Geroscience. 2024;46(3):3361–3375. doi: 10.1007/s11357-024-01064-9
  73. Domingos-Pereira S, Sathiyanadan K, La Rosa S, et al. Intravesical Ty21a vaccine promotes dendritic cells and T cell-mediated tumor regression in the MB49 bladder cancer model. Cancer Immunol Res. 2019;7(4):621–629. doi: 10.1158/2326-6066.CIR-18-0671
  74. Malaeva EG. Urinary tract infections and microbiota. Health and Ecology Issues. 2021;18(3):5–14. EDN: TQULMJ doi: 10.51523/2708-6011.2021-18-3-1
  75. Kyrgiou M, Mitra A, Moscicki A-B. Does the vaginal microbiota play a role in the development of cervical cancer? Transl Res. 2017;179:168–182. doi: 10.1016/j.trsl.2016.07.004
  76. Tashlanova VV, Kataeva LV, Stepanova TF. Species characteristics of bacteria of the genus Lactobacillus identified in different loci of the human body (literature review). Journal of microbiology, epidemiology and immunobiology. 2023;100(4):364–375. EDN: SBYXKC doi: 10.36233/0372-9311-332
  77. Suvorov AN. About us and our oncolytic bacteria. Nature. 2018;(8):3–9. EDN: YAMNJJ doi: 10.31857/S0032874X0000478-4
  78. Xu W, Yang L, Lee P, et al. Mini-review: perspective of the microbiome in the pathogenesis of urothelial carcinoma. Am J Clin Exp Urol. 2014;2(1):57–61.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2024 Eco-Vector

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
 


Согласие на обработку персональных данных с помощью сервиса «Яндекс.Метрика»

1. Я (далее – «Пользователь» или «Субъект персональных данных»), осуществляя использование сайта https://journals.rcsi.science/ (далее – «Сайт»), подтверждая свою полную дееспособность даю согласие на обработку персональных данных с использованием средств автоматизации Оператору - федеральному государственному бюджетному учреждению «Российский центр научной информации» (РЦНИ), далее – «Оператор», расположенному по адресу: 119991, г. Москва, Ленинский просп., д.32А, со следующими условиями.

2. Категории обрабатываемых данных: файлы «cookies» (куки-файлы). Файлы «cookie» – это небольшой текстовый файл, который веб-сервер может хранить в браузере Пользователя. Данные файлы веб-сервер загружает на устройство Пользователя при посещении им Сайта. При каждом следующем посещении Пользователем Сайта «cookie» файлы отправляются на Сайт Оператора. Данные файлы позволяют Сайту распознавать устройство Пользователя. Содержимое такого файла может как относиться, так и не относиться к персональным данным, в зависимости от того, содержит ли такой файл персональные данные или содержит обезличенные технические данные.

3. Цель обработки персональных данных: анализ пользовательской активности с помощью сервиса «Яндекс.Метрика».

4. Категории субъектов персональных данных: все Пользователи Сайта, которые дали согласие на обработку файлов «cookie».

5. Способы обработки: сбор, запись, систематизация, накопление, хранение, уточнение (обновление, изменение), извлечение, использование, передача (доступ, предоставление), блокирование, удаление, уничтожение персональных данных.

6. Срок обработки и хранения: до получения от Субъекта персональных данных требования о прекращении обработки/отзыва согласия.

7. Способ отзыва: заявление об отзыве в письменном виде путём его направления на адрес электронной почты Оператора: info@rcsi.science или путем письменного обращения по юридическому адресу: 119991, г. Москва, Ленинский просп., д.32А

8. Субъект персональных данных вправе запретить своему оборудованию прием этих данных или ограничить прием этих данных. При отказе от получения таких данных или при ограничении приема данных некоторые функции Сайта могут работать некорректно. Субъект персональных данных обязуется сам настроить свое оборудование таким способом, чтобы оно обеспечивало адекватный его желаниям режим работы и уровень защиты данных файлов «cookie», Оператор не предоставляет технологических и правовых консультаций на темы подобного характера.

9. Порядок уничтожения персональных данных при достижении цели их обработки или при наступлении иных законных оснований определяется Оператором в соответствии с законодательством Российской Федерации.

10. Я согласен/согласна квалифицировать в качестве своей простой электронной подписи под настоящим Согласием и под Политикой обработки персональных данных выполнение мною следующего действия на сайте: https://journals.rcsi.science/ нажатие мною на интерфейсе с текстом: «Сайт использует сервис «Яндекс.Метрика» (который использует файлы «cookie») на элемент с текстом «Принять и продолжить».