Вагинальный микробиом и роль пробиотиков в поддержании женского здоровья


DOI: https://dx.doi.org/10.18565/pharmateca.2024.5.30-38

Хрянин А.А., Кнорринг Г.Ю.

1) Новосибирский государственный медицинский университет, Новосибирск, Россия; 2) РОО «Ассоциация акушеров-гинекологов и дерматовенерологов», Новосибирск, Россия; 3) Российский университет медицины, Москва, Россия
Вагинальный микробиом в последние годы стал предметом многих научных исследований во всем мире. Поддержание стабильности микробиоценоза влагалища признается важным фактором сохранения здоровья, причем не только на локальном уровне, но и в целом для женского организма. Пробиотики широко используются при лечении кишечных заболеваний, однако их влияние на женское репродуктивное здоровье до сих пор остается спорным. Лактобактерии – наиболее распространенный микроорганизм во влагалище, связанный с его слизистым барьером. Лактобактерии прикрепляются к эпителию влагалища и могут конкурентно противодействовать колонизации различных уловно-патогенных микроорганизмов. Факторы, продуцируемые лактобактериями, такие как бактериоцин и перекись водорода, могут подавлять рост условно-патогенных микроорганизмов и поддерживать низкий уровень pH во влагалище. Пробиотики играют важную роль в поддержании стабильности микробиома влагалища и повышении иммунной защиты организма женщины. Авторы обсуждают современную роль пробиотиков, представленных Lactobacillus, при различных гинекологических заболеваниях, а также их значение для поддержания женского здоровья.

Литература


1. Cone R.A. Vaginal microbiota and sexually transmitted infections that may influence transmission of cell-associated HIV. J Infect Dis. 2014;210(3):S616–21. doi: 10.1093/infdis/jiu459.


2. Joag V., Obila O., Gajer P. et al. Impact of standard bacterial vaginosis treatment on the genital microbiota, immune milieu, and ex vivo human immunodeficiency virus susceptibility. Clin Infect Dis. 2019;68(10):1675–83. doi: 10.1093/cid/ciy762.


3. Petrova M.I., van der Broek M., Balzarini J., et al. Vaginal microbiota and its role in HIV transmission and infection. FEMS Microbiol Rev. 2013;37(5):762–92. doi: 10.1111/1574-6976.12029


4. Хрянин А.А., Кнорринг Г.Ю., Бочарова В.К. Нарушение вагинального микробиома и риск заражения ВИЧ-инфекцией у женщин. ВИЧ-инфекция и иммуносупрессии. 2023;15(1):23–31.


5. Mastromarino P., Hemalatha R., Barbonetti A., et al. Biological control of vaginosis to improve reproductive health. Indian J Med Res. 2014; 140(Suppl 1):S91–97.


6. Vanbelle M., Teller E., Focant M. Probiotics in animal nutrition: a review. Arch Tierernahr. 1990;40(7):543–67. doi: 10.1080/17450399009428406.


7. Савичева А.М., Рыбина Е.В. Исследование in vitro роста, размножения, антибиотикорезистентности, конкурентных взаимоотношений штамма Lactobacillus casei rhamnosus. Акушерство и гинекология. 2014;7:79–83.


8. Chee W.J.Y., Chew S.Y., Than, L.T.L. Vaginal microbiota and the potential of lactobacillus derivatives in maintaining vaginal health. Microb. Cell Fact. 2020;19(1):203. doi: 10.1186/s12934-020-01464-4.


9. Ma S., Wang W., Su Y., Sun W., Ma L. Antibiotics therapy combined with probiotics administered intravaginally for the treatment of bacterial vaginosis: A systematic review and meta-analysis. Open Med (Wars). 2023 Sep 13;18(1):20230644. doi: 10.1515/med-2023-0644.


10. Chieng W.K., Abdul Jalal M.I., Bedi J.S., et al. Probiotics, a promising therapy to reduce the recurrence of bacterial vaginosis in women? a systematic review and meta-analysis of randomized controlled trials. Front Nutr. 2022 Sep 20;9:938838. doi: 10.3389/fnut.2022.938838.


11. Lopez-Moreno A., Aguilera M. Vaginal Probiotics for Reproductive Health and Related Dysbiosis: Systematic Review and Meta-Analysis. J Clin Med. 2021 Apr 2;10(7):1461. doi: 10.3390/jcm10071461.


12. Wang Z., He Y., Zheng Y. Probiotics for the Treatment of Bacterial Vaginosis: A Meta-Analysis. Int J Environ Res Public Health. 2019 Oct 12;16(20):3859. doi: 10.3390/ijerph16203859.


13. Di Bella J.M., Bao Y., Gloor G.B., et al. High throughput sequencing methods and analysis for microbiome research. J Microbiol Methods. 2013;95(3):401–14. doi: 10.1016/j.mimet.2013.08.011.


14. Ravel J., Gajer P., Abdo, Z., et al. Vaginal microbiome of reproductive-age women. Proc Natl Acad Sci. U.S.A. 2011;108(1):4680–87. doi: 10.1073/pnas.1002611107.


15. Cohen C.R., Wierzbicki M.R., French A.L., et al. Randomized Trial of Lactin-V to Prevent Recurrence of Bacterial Vaginosis. N Engl J Med. 2020 May 14;382(20):1906–15. doi: 10.1056/NEJMoa1915254.


16. Petrova M.I., Reid G., Vaneechoutte M., Lebeer S. Lactobacillus iners: Friend or foe? Trends Microbiol. 2017;25(3):182–91. doi: 10.1016/j.tim.2016.11.007.


17. Kalia N., Singh J., Kaur M. Microbiota in vaginal health and pathogenesis of recurrent vulvovaginal infections: a critical review. Ann Clin Microbiol Antimicrob. 2020;19(1):5. doi: 10.1186/s12941-020-0347-4.


18. Peebles K., Velloza J., Balkus J.E., et al. High global burden and costs of bacterial vaginosis: a systematic review and meta-analysis. Sex Transm Dis. 2019;46;5:304–11. doi: 10.1097/OLQ.0000000000000972.


19. Hall R.A., Noverr M.C. Fungal interactions with the human host: exploring the spectrum of symbiosis. Curr Opin Microbiol. 2017;40:58–64. doi: 10.1016/j.mib.2017.10.020.


20. Parolin C., Frisco G., Foschis C., et al. Lactobacillus crispatus BC5 interferes with Сhlamydia trachomatis infectivity through integrin modulation in cervical cells. Front Microbiol. 2018;9:2630. doi: 10.3389/fmicb.2018.02630.


21. Calonghi N., Parolin C., Sartor G., et al. Interaction of vaginal lactobacillus strains with HeLa cells plasma membrane. Benef Microbes 2017;8(4):625–33. doi: 10.3389/fmicb.2018.02630.


22. Parolin C., Marangoni A., Laghi L., et al. Isolation of vaginal lactobacilli and characterization of anti-candida activity. PloS One. 2015;10(6):e0131220. doi: 10.1371/journal.pone.0131220.


23. Younes J.A., Lievens E., Hummelen R., et al. Women and their microbes: The unexpected friendship. Trends Microbiol. 2018;26(1):16–32. doi: 10.1016/j.tim.2017.07.008.


24. Jayaram P. M., Mohan M.K., Konje J. Bacterial vaginosis in pregnancy - a storm in the cup of tea. Eur J Obstet Gynecol Reprod Biol. 2020;253:220–24. doi: 10.1016/j.ejogrb.2020.08.009.


25. Amabebe E., Anumba D.O.C. The vaginal microenvironment: The physiologic role of lactobacilli. Front Med. (Lausanne) 2018;5:181. doi: 10.3389/fmed.2018.00181.


26. Nunn K.L., Wang Y.Y., Harit D., et al. Enhanced Trapping of HIV-1 by human cervicovaginal mucus is associated with Lactobacillus crispatus-dominant microbiota. mBio. 2015;6(5):e01084-15. doi: 10.1128/mBio.01084-15.


27. Kroon S.J., Ravel J., Huston W.M. Cervicovaginal microbiota, women’s health, and reproductive outcomes. Fertil Steril. 2018;110(3):327–36. doi: 10.1016/j.fertnstert.2018.06.036.


28. Tomusiak A., Strus M., Heczko P.B., et al. Efficacy and safety of a vaginal medicinal product containing three strains of probiotic bacteria: a multicenter, randomized, double-blind, and placebo-controlled trial. Drug Des Devel Ther. 2015;9:5345–54. Doi: 10.2147/DDDT.S89214.


29. Fichorova R.N., Morrison S.C., Chen P.L., et al. Aberrant cervical innate immunity predicts onset of dysbiosis and sexually transmitted infections in women of reproductive age. PLoS One. 2020;15(1):e0224359. doi: 10.1371/journal.pone.0224359.


30. Lallar M., Nanda S., Nandal R. Lower genital tract infections in HIV-infected women: can we afford to miss? J Obstet Gynaecol India. 2015;65:45–9. doi:10.1007/s13224-014-0604-6.


31. Хрянин А.А., Кнорринг Г.Ю. Бактериальный вагиноз: дискуссионные вопросы. Вестник дерматологии и венерологии. 2022;1:13–8.


32. Хрянин А.А., Кнорринг Г.Ю. Современные представления о бактериальном вагинозе. Гинекология. 2021;1:37–42.


33. McKinnon L.R., Achilles S.L., Bradshaw C.S., et al. The evolving facets of bacterial vaginosis: implications for HIV transmission. AIDS Res Hum Retroviruses. 2019;35(3):219–28. doi: 10.1089/AID.2018.0304.


34. Onderdonk A.B., Delaney M.L., Fichorova R.N. The human microbiome during bacterial vaginosis. Clin Microbiol Rev. 2016;29(2):223–38. doi:10.1128/CMR.00075-15.


35. Swidsinski A., Mendling W., Loening-Baucke V., et al. Adherent biofilms in bacterial vaginosis. Obstet Gynecol. 2005;106 (5 Pt 1):1013–23. doi: 10.1097/01.AOG.0000183594.45524.d2.


36. Javed A., Parvaiz F., Manzoor S. Bacterial vaginosis: an insight into the prevalence, alternative treatments regimen and it’s associated resistance patterns. Microb Pathog. 2019;127:21–30. doi: 10.1016/j.micpath.2018.11.046.


37. Bautista C.T., Wurapa E., Sateren W.B., et al. Bacterial vaginosis: a synthesis of the literature on etiology, prevalence, risk factors, and relationship with chlamydia and gonorrhea infections. Mil Med Res. 2016;3:4. doi: 10.1186/s40779-016-0074-5.


38. Mohanty S., Sood S, Kapil A., Mittal S. Interobserver variation in the interpretation of Nugent scoring method for diagnosis of bacterial vaginosis. Indian J Med Res. 2010;131:88Y91.


39. Parent D., Bossens M., Bayot D., et al. Therapy of bacterial vaginosis using exogenously-applied Lactobacillus aciophili and a low dose of estriol: a placebo-controlled multicentric clinical trial. Arzneimitell Forschung. 1996;46:68Y73.


40. Neut C., Verriere F., Nelis H.J., Coenye T. Topical treatment of infectious vaginitis: effects of antibiotic, antifungal and antiseptic drugs on the growth of normal vaginal lactobacillus strains. Open J Obstet Gynecol. 2015;5:173–80.


41. Redelinghuys M.J., Geldenhuys J., Jung H., Kock M.M. Bacterial vaginosis: current diagnostic avenues and future opportunities. Front Cell Infect Microbiol. 2020;10:354. doi: 10.3389/fcimb.2020.00354.


42. Mastromarino P., Vitali B., Mosca L. Bacterial vaginosis: a review on clinical trials with probiotics. New microbiologica. 2013;36:229–38.


43. Hoyme U.B., Huebner J. Prevention of preterm birth is possible by vaginal pH screening, early diagnosis of bacterial vaginosis or abnormal vaginal flora and treatment. Gynecol Obstet Invest. 2010;70:286Y90. doi: 10.1159/000314019.


44. Mendling W., Palmeira-de-Oliveira A., Biber S., Prasauskas V. An update on the role of Atopobium vaginae in bacterial vaginosis: what to consider when choosing a treatment? A mini review. Arch Gynecol Obstet. 2019;300(1):1–6. doi: 10.1007/s00404-019-05142-8.


45. Salinas A.M., Osorio V.G., Pacha-Herrera D., et al. Vaginal microbiota evaluation and prevalence of key pathogens in ecuadorian women: an epidemiologic analysis. Sci Rep. 2020;10:1. doi: 10.1038/s41598-020-74655-z.


46. Petersen C., Round J.L. Defining dysbiosis and its influence on host immunity and disease. Cell Microbiol. 2014;16:1024–33. doi: 10.1111/cmi.12308.


47. Chee W.J.Y., Chew S.Y., Than L.T.L. Vaginal microbiota and the potential of Lactobacillus derivatives in maintaining vaginal health. Microb Cell Fact. 2020;19:203. doi: 10.1186/s12934-020-01464-4.


48. Хрянин А.А. Биомаркеры бактериального вагиноза: аналитический обзор. Русский медицинский журнал. Мать и дитя. 2023;6(4):374–79.


49. van de Wijgert J.H., Borgdorff H., Verhelst R., et al. The vaginal microbiota: what have we learned after a decade of molecular characterization? PLoS One. 2014;9(8):e105998. doi: 10.1371/journal.pone.0105998


50. Vaneechoutte M., Guschin A., Van Simaey L., et al. Emended description of Gardnerella vaginalis and description of Gardnerella leopoldii sp. nov., Gardnerella piotii sp. nov. and Gardnerella swidsinskii sp. nov., with delineation of 13 genomic species within the genus Gardnerella. Int J Syst Evol Microbiol. 2019;69(3):679–87. doi: 10.1099/ijsem.0.003200.


51. Laniewski P., Ilhan Z. E., Herbst-Kralovetz M. M. The microbiome and gynaecological cancer development, prevention and therapy. Nat Rev Urol. 2020;17(4):232–50. doi: 10.1038/s41585-020-0286-z.


52. Piccioni A., Franza L., Vaccaro V., et al. Microbiota and probiotics: The role of limosilactobacillus reuteri in diverticulitis. Medicina (Kaunas). 2021;57(8):802. doi: 10.3390/medicina57080802.


53. Abdolalipour E., Mahooti M., Salehzadeh A., et al. Evaluation of the antitumor immune responses of probiotic bifidobacterium bifidum in human papillomavirus-induced tumor model. Microb Pathog. 2020;145:104207. doi: 10.1016/j.micpath.2020.104207.


54. Liu J., Luo M., Zhang Y., et al. Association of high-risk human papillomavirus infection duration and cervical lesions with vaginal microbiota composition. Ann Transl Med. 2020;8(18):1161. doi: 10.21037/atm-20-5832.


55. Kandati K., Belagal P., Nannepaga J.S., Viswanath B. Role of probiotics in the management of cervical cancer: An update. Clin Nutr ESPEN. 2022;48:5–16. doi: 10.1016/j.clnesp.2022.02.017.


56. Medina-Contreras O., Luvián-Morales J., Valdez-Palomares F., et al. Immunonutrition in cervical cancer immune response modulation by diet. Rev Invest Clin. 2020;72(4): 19–230. doi: 10.24875/RIC.20000062.


57. Wang H., Ma Y., Li R., et al. Associations of cervicovaginal lactobacilli with high-risk human papillomavirus infection, cervical intraepithelial neoplasia, and cancer: A systematic review and meta-analysis. J Infect Dis. 2019;220(8):1243–54. doi: 10.1093/infdis/jiz325.


58. Российское общество акушеров-гинекологов (РОАГ). Клинические рекомендации по диагностике и лечению заболеваний, сопровождающихся патологическими выделениями из половых путей женщин. 2-е изд., испр. и доп. Москва, 2019. 56 с.


59. Homayouni A., Bastani P., Ziyadi S., et al. Effects of probiotics on the recurrence of bacterial vaginosis: a review. J Low Genit Tract Dis. 2014;18(1):79–86. doi: 10.1097/LGT.0b013e31829156ec.


60. Hemalatha R., Ramalaxmi B.A., Swetha E., et al. Evaluation of vaginal pH for detection of bacterial vaginosis. Indian J Med Res. 2013;138(3):354–59.


61. Bohbot J.M., Daraп E., Bretelle F., et al. Efficacy and safety of vaginally administered lyophilized Lactobacillus crispatus IP 174178 in the prevention of bacterial vaginosis recurrence. J Gynecol Obstet Hum Reprod. 2018;47(2):81–6. doi: 10.1016/j.jogoh.2017.11.005.


62. Sherrard J., Wilson J., Donders G., et al. European (IUSTI/WHO) International Union against sexually transmitted infections (IUSTI) World Health Organisation (WHO) guideline on the management of vaginal discharge. Int J STD AIDS. 2018;29(13):1258–72. doi: 10.1177/0956462418785451.


63. CDC. Centers for Disease Control and Prevention. Sexually Transmitted Infections Treatment Guidelines. Morbidity and Mortality Weekly Report: Recommendations and Reports. 2021;70(4). Authors: Workowski K.A., Bachmann L.H., Chan P.A., Johnston C.M., Muzny C.A., et al. 2021. 187 р.


64. AEProbio (the Alliance for Education on Probiotics). Clinical Guide to Probiotic Products Available in Canada: 15th Ed. 2023. D. Skokovic-Sunjic, Ed. R.L. Johnson. 2023. 24 p.


65. Клинические рекомендации МЗ РФ «Бактериальный вагиноз», 2022. URL: https://cr.minzdrav.gov.ru/schema/194_1


66. Farr A., Swidsinski S., Surbek D., et al. Bacterial Vaginosis: Guideline of the DGGG, OEGGG and SGGG (S2k-Level, AWMF Registry No. 015/028, June 2023). Geburtshilfe Frauenheilkd. 2023;83(11):1331–49. doi: 10.1055/a-2169-8539.


67. Mei Z., Li D. The role of probiotics in vaginal health. Front Cell Infect Microbiol. 2022;12:963868. doi: 10.3389/fcimb.2022.963868.


68. Denning D.W., Kneale M., Sobel J.D., Rautemaa-Richardson R. Global burden of recurrent vulvovaginal candidiasis: a systematic review. Lancet Infect Dis. 2018;18(11):e339–e347. doi: 10.1016/S1473-3099(18)30103-8.


69. Farr A., Effendy I., Frey Tirri B., et al. Guideline: Vulvovaginal candidosis (AWMF 015/072, level S2k). Mycoses. 2021;64(6):583–602. doi: 10.1111/myc.13248.


70. Matheson A., Mazza D. Recurrent vulvovaginal candidiasis: A review of guideline recommendations. Aust N Z J. Obstet Gynaecol. 2017;57(2):139–45. doi: 10.1111/ajo.12592.


71. Liu M.B., Xu S.R., He Y., et al. Diverse vaginal microbiomes in reproductive-age women with vulvovaginal candidiasis. PloS One. 2013;8(11):e79812. doi: 10.1371/journal.pone.0079812.


72. Ceccarani C., Foschi C., Parolin C., et al. Diversity of vaginal microbiome and metabolome during genital infections. Sci Rep. 2019;9(1),14095. doi: 10.1038/s41598-019-50410-x.


73. Balakrishnan S.N., Yamang H., Lorenz M. C., et al. Role of vaginal mucosa, host immunity and microbiota in vulvovaginal candidiasis. Pathogens. 2022;11(6):618. doi: 10.3390/pathogens11060618.


74. Wang S., Wang Q., Yang E., et al. Antimicrobial compounds produced by vaginal lactobacillus crispatus are able to strongly inhibit Сandida albicans growth, hyphal formation and regulate virulence-related gene expressions. Front Microbiol. 2017;8:564. doi: 10.3389/fmicb.2017.00564.


75. Fuochi V., Cardile V., Petronio Petronio G., Furneri P.M. Biological properties and production of bacteriocins-like-inhibitory substances by lactobacillus spp. strains from human vagina. J Appl Microbiol. 2019;126(5):1541–50. doi: 10.1111/jam.14164.


76. Okkers D.J., Dicks L.M., Silvester M., et al. Characterization of pentocin TV35b, a bacteriocin-like peptide isolated from lactobacillus pentosus with a fungistatic effect on Сandida albicans. J Appl Microbiol. 1999;87(5):726–34. doi: 10.1046/j.1365-2672.1999.00918.x.


77. Osset J., Garcia E., Bartolome R.M., Andreu A. Role of lactobacillus as protector against vaginal candidiasis. Med Clin (Barc). 2001;117(8):285–88. doi: 10.1016/s0025-7753(01)72089-1.


78. Strus M., Brzychczy-Wloch M., Kucharska A., et al. Inhibitory activity of vaginal lactobacillus bacteria on yeasts causing vulvovaginal candidiasis. Med Dosw Mikrobiol 2005;57(1):7–17.


79. Santos C.M., Pires M.C., Leao T.L., et al. Selection of lactobacillus strains as potential probiotics for vaginitis treatment. Microbiol. (Reading). 2016;162(7):1195–207. doi: 10.1099/mic.0.000302.


80. Li T., Liu Z., Zhang X., et al. Local probiotic Lactobacillus crispatus and Lactobacillus delbrueckii exhibit strong antifungal effects against vulvovaginal candidiasis in a rat model. Front Microbiol. 2019;10:1033. doi: 10.3389/fmicb.2019.01033.


81. MacAlpine J., Daniel-Ivad M., Liu Z., et al. A small molecule produced by lactobacillus species blocks Сandida albicans filamentation by inhibiting a DYRK1-family kinase. Nat Commun. 2021;12(1):6151. doi: 10.1038/s41467-021-26390-w.


82. Hefzy E.M., Khalil M.A.F., Amin A.A.I., et al. Bacteriocin-like inhibitory substances from probiotics as therapeutic agents for candida vulvovaginitis. Antibiotics (Basel). 2021;10(3):306. doi: 10.3390/antibiotics10030306.


83. Paniagua A.L., Correia A.F., Pereira L.C., et al. Inhibitory effects of Lactobacillus casei shirota against both Candida auris and Candida spp. isolates that cause vulvovaginal candidiasis and are resistant to antifungals. BMC Complement Med Ther. 2021;21(1):237. doi: 10.1186/s12906-021-03405-z.


84. Reid G., Charbonneau D., Erb J., et al. Oral use of Lactobacillus rhamnosus GR-1 and L. fermentum RC-14 significantly alters vaginal flora: randomized, placebo-controlled trial in 64 healthy women. FEMS Immunol. Med Microbiol. 2003;35(2):131–34. doi: 10.1016/S0928-8244(02)00465-0.


85. De Seta F., Parazzini F., De Leo R., et al. Lactobacillus plantarum P17630 for preventing candida vaginitis recurrence: a retrospective comparative study. Eur J Obstet Gynecol Reprod Biol. 2014;182:136–39. doi: 10.1016/j.ejogrb.2014.09.018.


86. Morelli L., Zonenenschain D., Del Piano M., Cognein P. Utilization of the intestinal tract as a delivery system for urogenital probiotics. J Clin Gastroenterol. 2004;38(6 Suppl):S107–10. doi: 10.1097/01.mcg.0000128938.32835.98.


87. Хрянин А.А., Жукова А.И. Вагинальная микробиота и репродуктивное здоровье: грани проблемы. Status Praesens. Гинекология, акушерство, бесплодный брак. 2024;1(104):51–4.


Об авторах / Для корреспонденции


Автор для связи: Алексей Алексеевич Хрянин, д.м.н., профессор кафедры дерматовенерологии и косметологии, Новосибирский государственный медицинский университет, президент РОО «Ассоциация акушеров-гинекологов и дерматовенерологов», Новосибирск, Россия; khryanin@mail.ru


ORCID: 
А.А. Хрянин (A.A. Khryanin), https://orcid.org/0000-0001-9248-8303
Г.Ю. Кнорринг (G.Yu. Knorring), https://orcid.org/0000-0003-4391-2889


Похожие статьи


Бионика Медиа