Влияние микробиома человека на развитие рака предстательной железы

   Растущее количество данных свидетельствует о значимой роли микробиома человека, особенно кишечного и урогенитального тракта, в развитии и прогрессировании различных онкологических заболеваний, включая рак предстательной железы. Дисбиоз микробиоты может модулировать локальное и системное воспаление, метаболизм гормонов и канцерогенез.

   Цель – обобщить современные знания о взаимосвязи между дисбиозом микробиома и риском развития рака предстательной железы.

   Обзор литературы демонстрирует, что специфические изменения в составе микробиоты кишечника и мочевыводящих путей ассоциированы с риском развития РПЖ. Ключевые механизмы включают: индукцию хронического воспаления, продукцию микробных метаболитов, влияющих на пролиферацию клеток и сигнальные пути, модуляцию иммунного ответа хозяина и потенциальное влияние на метаболизм андрогенов и эстрогенов.

1. Злокачественные новообразования в России в 2021 году (заболеваемость и смертность). Под ред. А.Д. Каприна, В.В. Старинского, А.О. Шахзадовой. М.: МНИОИ им. П.А. Герцена − филиал ФГБУ «НМИЦ радиологии» Минздрава России, 2022. 252 с.

2. Global cancer observatory. WHO IARC.-URL: https://gco.iarc.fr/ (18. 02. 2024).

3. Pernar C.H., Ebot E.M., Wilson K.M, Mucci LA. The Epidemiology of Prostate Cancer. Cold Spring Harb Perspect Med. 2018 Dec 3;8(12):a030361. doi: 10.1101/cshperspect.a030361. PMID: 29311132; PMCID: PMC6280714.

4. Киприянов Е.А., Карнаух П.А., Важенин И.А. и др. Эффективность применения лучевых методов лечения пациентов с локализованным раком предстательной железы в условиях одного стационара. Онкоурология. 2017; 13(2): 74-78. doi: 10.17650/1726-9776-2017-13-2- 74-78.

5. Wang Y., Gieschen H., Greenberger M. et al. Survival after robotic-assisted prostatectomy for localized prostate cancer: an epidemiologic study. Ann Surg. 2021; 274(6): e507-e514. doi: 10.1097/SLA.0000000000003637. PMID: 31663972.

6. Siegel R.L., Miller K.D., Fuchs H.E., Jemal A. Cancer Statistics, 2021. CA Cancer J Clin. 2021 Jan;71(1):7-33. doi: 10.3322/caac.21654. Epub 2021 Jan 12. Erratum in: CA Cancer J Clin. 2021 Jul;71(4):359. doi: 10.3322/caac.21669. PMID: 33433946.

7. Poore G.D., Kopylova E., Zhu Q. et al. Microbiome Analyses of Blood and Tissues Suggest Cancer Diagnostic Approach. Nature (2020) 579:567–74. doi: 10.1038/s41586-020-2095-1.

8. Аляев Ю.Г., Винаров А.З., Фиев Д.Н. и др. Возможно ли влияние микоплазменной инфекции на патогенез рака предстательной железы.? Онкоурология. 2010;6(1):28-32. doi: 10.17650/1726-9776-2010-6-1-28-32.

9. Sfanos K.S., Yegnasubramanian S., Nelson W.G., De Marzo A.M. The inflammatory microenvironment and microbiome in prostate cancer development. Nat. Rev. Urol. 2018; Jan;15(1):11-24. doi: 10.1038/nrurol.2017.167. Epub 2017 Oct 31. PMID: 29089606.

10. Colotta F., Allavena P., Sica A. et al. Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability. Carcinogenesis. 2009 Jul;30(7):1073-81. doi: 10.1093/carcin/bgp127. Epub 2009 May 25. PMID: 19468060.

11. Kistowska M., Meier B., Proust T. et al. Propionibacterium acnes promotes Th17 and Th17/Th1 responses in acne patients. J Invest Dermatol. 2015 Jan;135(1):110-118. doi: 10.1038/jid.2014.290. Epub 2014 Jul 10. PMID: 25010142.

12. Sellami H., Said-Sadier N., Znazen A. et al. Chlamydia trachomatis infection increases the expression of inflammatory tumorigenic cytokines and chemokines as well as components of the Toll-like receptor and NF-κB pathways in human prostate epithelial cells. Mol Cell Probes. 2014 Aug;28(4):147-54. doi: 10.1016/j.mcp.2014.01.006. Epub 2014 Mar 12. PMID: 24613856.

13. Banerjee S., Alwine J.C., Wei Z. et al. Microbiome signatures in prostate cancer. Carcinogenesis. 2019; Jul 6; 40(6):749-764. doi: 10.1093/carcin/bgz008. PMID: 30794288.

14. Клинические рекомендации по андрологической урологии / под ред. П. А. Щеплева. М.: Медфорум. 2016. 120 с.

15. Funahashi Y., Majima T., Matsukawa Y. et al. Reflux of Urine Induces Inflammation in a Rat. Prostate. 2017 Feb;77(2):164-172. doi: 10.1002/pros.23257. Epub 2016 Sep 29. PMID: 27683251.

16. Shrestha E., White J.R., Yu S.H. et al. Profiling the Urinary Microbiome in Men with Positive versus Negative Biopsies for Prostate Cancer. J Urol. 2018 Jan;199(1):161-171. doi: 10.1016/j.juro.2017.08.001. Epub 2017 Aug 7. PMID: 28797714; PMCID: PMC5937117.

17. Hurst R., Meader E., Gihawi A. et al. Microbiomes of Urine and the Prostate Are Linked to Human Prostate Cancer Risk Groups. Eur Urol Oncol. 2022 Aug;5(4):412-419. doi: 10.1016/j.euo.2022.03.006. Epub 2022 Apr 18. PMID: 35450835.

18. Tsai K.Y., Wu D.C., Wu W.J. et al. Exploring the Association between Gut and Urine Microbiota and Prostatic Disease including Benign Prostatic Hyperplasia and Prostate Cancer Using 16S rRNA Sequencing. Biomedicines. 2022 Oct 23;10(11):2676. doi: 10.3390/biomedicines10112676. PMID: 36359196; PMCID: PMC9687995.

19. Alanee S., El-Zawahry A., Dynda D. et al. 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. 2019 Jan;79(1):81-87. doi: 10.1002/pros.23713. Epub 2018 Aug 16. PMID: 30117171.

20. Barykova Y.A., Logunov D.Y., Vinarov A.Z. et al. Association of Mycoplasma hominis infection with prostate cancer. Oncotarget. 2011 Apr;2(4):289-97. doi: 10.18632/oncotarget.256. PMID: 21471611; PMCID: PMC3248169.

21. Johnson A.O., Forsyth V., Smith S.N. et al. Transposon Insertion Site Sequencing of Providencia stuartii: Essential Genes, Fitness Factors for Catheter-Associated Urinary Tract Infection, and the Impact of Polymicrobial Infection on Fitness Requirements. mSphere. 2020 May 27;5(3):e00412-20. doi: 10.1128/mSphere.00412-20. PMID: 32461277; PMCID: PMC7253602.

22. Hooton T.M., Bradley S.F., Cardenas D.D. et al. Diagnosis, prevention, and treatment of catheter-associated urinary tract infection in adults: 2009 International Clinical Practice Guidelines from the Infectious Diseases Society of America. Clin Infect Dis. 2010 Mar 1;50(5):625-63. doi: 10.1086/650482. PMID: 20175247.

23. Morris N.S., Stickler D.J., McLean R.J. The development of bacterial biofilms on indwelling urethral catheters. World J Urol. 1999 Dec;17(6):345-50. doi: 10.1007/s003450050159. PMID: 10654364.

24. Vázquez-Salas R.A., Torres-Sánchez L., López-Carrillo L. et al. History of gonorrhea and prostate cancer in a population-based case-control study in Mexico. Cancer Epidemiol. 2016 Feb;40:95-101. doi: 10.1016/j.canep.2015.12.001. Epub 2015 Dec 17. PMID: 26706364.

25. Huang W.Y., Hayes R., Pfeiffer R. et al. Sexually transmissible infections and prostate cancer risk. Cancer Epidemiol Biomarkers Prev. 2008 Sep;17(9):2374-81. doi: 10.1158/1055-9965.EPI-08-0173. PMID: 18768506; PMCID: PMC2559953.

26. Sarma A.V., McLaughlin J.C., Wallner L.P. et al. Sexual behavior, sexually transmitted diseases and prostatitis: the risk of prostate cancer in black men. J Urol. 2006 Sep;176(3):1108-13. doi: 10.1016/j.juro.2006.04.075. PMID: 16890703.

27. Benli E., Yuce A., Cirakoglu A. et al. Comparison of Sexual Behavior and Inflammatory Parameters in Prostate Cancer Patients with Control Group: Prospective Controlled Study. Urol J. 2022 May 15;19(2):101-105. doi: 10.22037/uj.v18i.6464. PMID: 34302738.

28. Han I.H., Song H.O., Ryu J.S. IL-6 produced by prostate epithelial cells stimulated with Trichomonas vaginalis promotes proliferation of prostate cancer cells by inducing M2 polarization of THP-1-derived macrophages. PLoS Negl Trop Dis. 2020 Mar 20;14(3):e0008126. doi: 10.1371/journal.pntd.0008126. PMID: 32196489; PMCID: PMC7138318.

29. Kushwaha B., Devi A., Maikhuri J.P. et al. Inflammation driven tumor-like signaling in prostatic epithelial cells by sexually transmitted Trichomonas vaginalis. Int J Urol. 2021 Feb;28(2):225-240. doi: 10.1111/iju.14431. Epub 2020 Nov 30. PMID: 33251708.

30. Ma J., Gnanasekar A., Lee A. et al. Influence of Intratumor Microbiome on Clinical Outcome and Immune Processes in Prostate Cancer. Cancers (Basel). 2020 Sep 5;12(9):2524. doi: 10.3390/cancers12092524. PMID: 32899474; PMCID: PMC7564876.

31. Petyaev I.M., Zigangirova N.A., Morgunova E.Y. et al. Chlamydia trachomatis Growth and Cytokine mRNA Response in a Prostate Cancer Cell Line. Adv Urol. 2019 Jan 17;2019:6287057. doi: 10.1155/2019/6287057. PMID: 30800160; PMCID: PMC6360031.

32. Abidi S.H., Bilwani F., Ghias K., Abbas F. Viral etiology of prostate cancer: Genetic alterations and immune response. A literature review. Int J Surg. 2018 Apr;52:136-140. doi: 10.1016/j.ijsu.2018.02.050. Epub 2018 Feb 26. PMID: 29496646.

33. Lawson J.S., Glenn W.K. Evidence for a causal role by human papillomaviruses in prostate cancer - a systematic review. Infect Agent Cancer. 2020 Jul 14;15:41. doi: 10.1186/s13027-020-00305-8. PMID: 32684946; PMCID: PMC7359253.

34. Fatemipour M., Nahand J.S., Fard Azar M.E. et al. Human papillomavirus and prostate cancer: The role of viral expressed proteins in the inhibition of anoikis and induction of metastasis. Microb Pathog. 2021 Mar;152:104576. doi: 10.1016/j.micpath.2020.104576. Epub 2020 Oct 18. Erratum in: Microb Pathog. 2023 Mar;176:105998. doi: 10.1016/j.micpath.2023.105998. PMID: 33086103.

35. Nahand J.S., Khanaliha K., Mirzaei H. et al. Possible role of HPV/EBV coinfection in anoikis resistance and development in prostate cancer. BMC Cancer. 2021 Aug 17;21(1):926. doi: 10.1186/s12885-021-08658-y. PMID: 34399719; PMCID: PMC8369687.

36. Whitaker N.J., Glenn W.K., Sahrudin A. et al. Human papillomavirus and Epstein Barr virus in prostate cancer: Koilocytes indicate potential oncogenic influences of human papillomavirus in prostate cancer. Prostate. 2013 Feb 15;73(3):236-41. doi: 10.1002/pros.22562. Epub 2012 Jul 31. PMID: 22851253.

37. Камалов А.А., Михалева Л.М., Карпов В.К. и др. Вирусный микробиом ткани предстательной железы при доброкачественной гиперплазии и раке предстательной железы. Онкоурология. 2025;21(1):25-34. doi: 10.17650/1726-9776-2025-21-1-25-34.

38. Wise G.J., Shteynshlyuger A. How to diagnose and treat fungal infections in chronic prostatitis. Curr Urol Rep. 2006 Jul;7(4):320-8. doi: 10.1007/s11934-996-0012-2. PMID: 16930504.

39. Hullar M.A., Burnett-Hartman A.N., Lampe J.W. Gut microbes, diet, and cancer. Cancer Treat Res. 2014;159:377-99. doi: 10.1007/978-3-642-38007-5_22. PMID: 24114492; PMCID: PMC4121395.

40. Golombos D.M., Ayangbesan A., O’Malley P. et al. The Role of Gut Microbiome in the Pathogenesis of Prostate Cancer: A Prospective, Pilot Study. Urology. 2018 Jan;111:122-128. doi: 10.1016/j.urology.2017.08.039. Epub 2017 Sep 6. PMID: 28888753.

41. Zhang J., Yi M., Zha L, Chen S. et al. (2016) Sodium Butyrate Induces Endoplasmic Reticulum Stress and Autophagy in Colorectal Cells: Implications for Apoptosis. PLoS ONE 11(1):e0147218. doi: 10.1371/journal.pone.0147218.

42. Wei W., Sun W., Yu S. et al. Butyrate production from high-fiber diet protects against lymphoma tumor. Leuk Lymphoma. 2016 Oct;57(10):2401-8. doi: 10.3109/10428194.2016.1144879. Epub 2016 Feb 17. PMID: 26885564.

43. Liss M.A., White J.R., Goros M. et al. Metabolic Biosynthesis Pathways Identified from Fecal Microbiome Associated with Prostate Cancer. Eur Urol. 2018 Nov;74(5):575-582. doi: 10.1016/j.eururo.2018.06.033. Epub 2018 Jul 12. PMID: 30007819; PMCID: PMC6716160.

44. Choi S.W., Mason J.B. Folate status: effects on pathways of colorectal carcinogenesis. J Nutr. 2002 Aug;132(8 Suppl):2413S-2418S. doi: 10.1093/jn/132.8.2413S. PMID: 12163703.

45. Figueiredo J.C., Grau M.V., Haile R.W. et al. Folic acid and risk of prostate cancer: results from a randomized clinical trial. J Natl Cancer Inst. 2009 Mar 18;101(6):432-5. doi: 10.1093/jnci/djp019. Epub 2009 Mar 10. PMID: 19276452; PMCID: PMC2657096.

46. Crocetto F., Boccellino M., Barone B. et al. The Crosstalk between Prostate Cancer and Microbiota Inflammation: Nutraceutical Products Are Useful to Balance This Interplay? Nutrients. 2020 Aug 31;12(9):2648. doi: 10.3390/nu12092648. PMID: 32878054; PMCID: PMC7551491.

47. Shoemaker R., Kim J. Urobiome: An outlook on the metagenome of urological diseases. Investig Clin Urol. 2021 Nov;62(6):611-622. doi: 10.4111/icu.20210312. PMID: 34729961; PMCID: PMC8566783.

48. Petrelli F., Ghidini M., Ghidini A. et al. Use of Antibiotics and Risk of Cancer : A Systematic Review and Meta-Analysis of Observational Studies. Cancers (Basel). 2019 Aug 14;11(8):1174. doi: 10.3390/cancers11081174. PMID: 31416208; PMCID: PMC6721461.

49. Boursi B., Mamtani R., Haynes K., Yang Y.X. Recurrent antibiotic exposure may promote cancer formation -- Another step in understanding the role of the human microbiota? Eur J Cancer. 2015 Nov;51(17):2655-64. doi: 10.1016/j.ejca.2015.08.015. Epub 2015 Aug 31. PMID: 26338196; PMCID: PMC4663115.

50. Tulstrup M.V., Christensen E.G., Carvalho V. et al. Antibiotic Treatment Affects Intestinal Permeability and Gut Microbial Composition in Wistar Rats Dependent on Antibiotic Class. PLoS One. 2015 Dec 21;10(12):e0144854. doi: 10.1371/journal.pone.0144854. PMID: 26691591; PMCID: PMC4686753.

51. Erridge C., Attina T., Spickett C.M., Webb D.J. A high-fat meal induces low-grade endotoxemia: evidence of a novel mechanism of postprandial inflammation. Am J Clin Nutr. 2007 Nov;86(5):1286-92. doi: 10.1093/ajcn/86.5.1286. PMID: 17991637.

52. Levels J.H., Abraham P.R., van den Ende A., van Deventer S.J. Distribution and kinetics of lipoprotein-bound endotoxin. Infect Immun. 2001 May;69(5):2821-8. doi: 10.1128/IAI.69.5.2821-2828.2001. PMID: 11292694; PMCID: PMC98230.

53. Matsushita M., Fujita K., Hatano K. et al. High-fat diet promotes prostate cancer growth through histamine signaling. Int J Cancer. 2022 Aug 15;151(4):623-636. doi: 10.1002/ijc.34028. Epub 2022 Apr 26. PMID: 35403732.

54. Bahmad H.F., Jalloul M., Azar J. et al. Tumor Microenvironment in Prostate Cancer: Toward Identification of Novel Molecular Biomarkers for Diagnosis, Prognosis, and Therapy Development. Front Genet. 2021 Mar 26;12:652747. doi: 10.3389/fgene.2021.652747. PMID: 33841508; PMCID: PMC8033163.

55. De Marzo A.M., Marchi V.L., Epstein J.I., Nelson W.G. Proliferative inflammatory atrophy of the prostate: implications for prostatic carcinogenesis. Am J Pathol. 1999 Dec;155(6):1985-92. doi: 10.1016/S0002-9440(10)65517-4. PMID: 10595928; PMCID: PMC1866955.

56. Lee S.H., Jia S., Zhu Y. et al. Transgenic expression of polyomavirus middle T antigen in the mouse prostate gives rise to carcinoma. J Virol. 2011 Jun;85(11):5581-92. doi: 10.1128/JVI.02609-10. Epub 2011 Mar 16. PMID: 21411524; PMCID: PMC3094993.

57. Elkahwaji J.E., Zhong W., Hopkins W.J., Bushman W. Chronic bacterial infection and inflammation incite reactive hyperplasia in a mouse model of chronic prostatitis. Prostate. 2007 Jan 1;67(1):14-21. doi: 10.1002/pros.20445. PMID: 17075821.

58. Doat S., Cénée S., Trétarre B. et al. Nonsteroidal anti-inflammatory drugs (NSAIDs) and prostate cancer risk: results from the EPICAP study. Cancer Med. 2017 Oct;6(10):2461-2470. doi: 10.1002/cam4.1186. Epub 2017 Sep 21. PMID: 28941222; PMCID: PMC5633590.

59. Salinas C.A., Kwon E.M., FitzGerald L.M. et al. Use of aspirin and other nonsteroidal antiinflammatory medications in relation to prostate cancer risk. Am J Epidemiol. 2010 Sep 1;172(5):578-90. doi: 10.1093/aje/kwq175. Epub 2010 Aug 5. PMID: 20688905; PMCID: PMC2950822.