Dysbiotic disorders and innate immunity indices in bacterial vaginosis

Uruimagova A.T., Prilepskaya V.N., Mezhevitinova E.A., Donnikov A.E., Attoeva D.I.

Academician V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia, Moscow, Russia
Bacterial vaginosis (BV) is one of the most common causes of abnormal vaginal discharge in reproductive-aged women. Currently, BV is generally recognized to be characterized by an increased growth of obligate and facultative anaerobic microorganisms in the vagina, causing the lactobacilli to be replaced by opportunistic pathogenic microorganisms (OPMs) and the vaginal pH to rise. The microbiota of human open cavities (the urogenital, intestinal, and respiratory tracts, and skin) is believed to be a unified complex; however, the mechanisms of interaction of microorganisms of in the above niches with the host have not yet been fully studied. It is still unclear why there is an imbalance in the vaginal microbiota and why most women with BV have a very weak immune response without pronounced signs of inflammation.
The representatives of OPMs are known to have mechanisms that can suppress or change the host’s immune responses, largely depending on polymorphisms in the genes of the immune system. There is evidence that genetic variations in the immune molecules play an important role in how a woman responds to changes in the composition of the vaginal microbiota. Recently, a number of researchers have supported the theory that in the absence of clinical manifestations, the vaginal microbiota characterized by the replacement of lactobacilli by OPMs can be considered normal. In addition, it is assumed that it is the host’s immune system that determines the clinical presentations and outcome of the disease; attention should be therefore paid not only to the vaginal microbiota, but also to the assessment of the local immune status of the host.
Conclusion: Thus, analyzing the data available in the world literature can lead to the conclusion that female innate immunity plays an important and possibly primary role in the development of BV, which affects the qualitative and quantitative composition of the microbiota of various localizations. Genetic variations in innate immunity factors can affect how a woman responds to changes in the composition of the vaginal microbiota, regulating the course of the process and clinical outcome.


bacterial vaginosis
recurrent bacterial vaginosis
vaginal microbiota
gut microbiota
polymorphism in the immune response gene
innate local immunity
pro-inflammatory cytokines
anti-inflammatory cytokines


  1. Филимонова Т.М., Елисютина О.Г., Ниязов Д.Д., Болдырева М.Н., Бурменская О.В., Реброва О.Ю. Локальный и системный иммунный ответ у больных тяжелым атопическим дерматитом. Российский аллергологический журнал. 2011; 5: 10-5. [Filimonova T. M., Elisyutina O. G., Niyazov D. D., Boldyreva M. N., Burmenskaya O. V., Rebrova O. Yu. Local and systemic immune response in patients with severe atopic dermatitis. Russian Allergological Journal. 2011; 5: 10-5. (in Russian)].
  2. Кунгурцева Е.А., Попкова С.М., Лещенко О.Я. Взаимоформирование микрофлоры слизистых оболочек открытых полостей различных биотопов у женщин как важный фактор их репродуктивного здоровья. Вестник РАМН. 2014; 69(9-10): 27-32. [Kungurtseva E.A., Popkova S.M., Leshchenko O.Y. Reciprocal formation of mucosal microflora of open cavities of different habitats in women as an important factor of their reproductive health. Annals of the Russian academy of medical sciences. 2014; 69(9-10): 27-32. (in Russian)]. https://dx.doi.org/10.15690/vramn.v69i9-10.1128.
  3. Suresh A., Rajesh A., Bhat R.M., Rai Y. Cytolytic vaginosis: a review. Indian. J. Sex. Transm. Dis. AIDS. 2009; 30(1): 48‐50. https://dx.doi.org/10.4103/0253-7184.55490.
  4. Mendling W. Vaginal microbiota. Adv. Exp. Med. Biol. 2016; 902: 83‐93. https://dx.doi.org/10.1007/978-3-319-31248-4_6.
  5. Tachedjian G., O’Hanlon D.E., Ravel J. The implausible “in vivo” role of hydrogen peroxide as an antimicrobial factor produced by vaginal microbiota. Microbiome. 2018; 6(1): 29. https://dx.doi.org/10.1186/s40168-018-0418-3.
  6. Donders G.G., Van Calsteren K., Bellen G., Reybrouck R., Van den Bosch T., Riphagen I., Van Lierde S. Predictive value for preterm birth of abnormal vaginal flora, bacterial vaginosis and aerobic vaginitis during the first trimester of pregnancy. BJOG. 2009; 116(10): 1315-24. https://dx.doi.org/10.1111/j.1471-0528.2009.02237.x.
  7. Witkin S.S., Mendes-Soares H., Linhares I.M., Jayaram A., Ledger W.J., Forney L.J. Influence of vaginal bacteria and D- and L-lactic acid isomers on vaginal extracellular matrix metalloproteinase inducer: implications for protection against upper genital tract infections. mBio. 2013; 4(4): e00460-13. https://dx.doi.org/10.1128/mBio.00460-13.
  8. Linhares I.M., Summers P.R., Larsen B., Giraldo P.C., Witkin S.S. Contemporary perspectives on vaginal pH and lactobacilli. Am. J. Obstet. Gynecol. 2011; 204(2): 120. e1-5. https://dx.doi.org/10.1016/j.ajog.2010.07.010.
  9. Petrova M.I., Reid G., Vaneechoutte M., Lebeer S. Lactobacillus iners: friend or foe? Trends Microbiol. 2017; 25(3): 182‐91. https://dx.doi.org/10.1016/j.tim.2016.11.007.
  10. Дикке Г.Б. Бактериальный вагиноз: новые аспекты этиопатогенеза и выбора терапевтических стратегий. РМЖ. Мать и дитя. 2019; 4: 307-13. [Dikke G.B. Bacterial vaginosis: new aspects of etiopathogenesis and the choice of therapeutic strategies. RMJ. Mother and Child. 2019; 4: 307-13 (in Russian)].
  11. Borgdorff H., Armstrong S.D., Tytgat H.L., Xia D., Ndayisaba G.F., Wastling J.M., van de Wijgert J.H. Unique insights in the cervicovaginal Lactobacillus iners and L. crispatus Proteomes and their associations with microbiota dysbiosis. PLoS One. 2016; 11(3): e0150767. https://dx.doi.org/10.1371/journal.pone.0150767.
  12. Machado A., Cerca N. Influence of biofilm formation by Gardnerella vaginalis and other anaerobes on bacterial vaginosis. J. Infect. Dis. 2015; 212(12):1856-61. https://dx.doi.org/10.1093/infdis/jiv338.
  13. Припутневич Т.В., Муравьева В.В., Гордеев А.Б. Молекулярно-генетические и фенотипические особенности синантропных и патогенных штаммов Gardnerella vaginalis. Акушерство и гинекология. 2019: 3: 10-7. [Priputnevich T.V., Muravieva V.V., Gordeev A.B. The molecular-genetic and phenotypic features of synanthropic and pathogenic Gardnerella vaginalis strains. Obstetrics and Gynecology. 2019: 3: 10-7. (in Russian)]. https://dx.doi.org/10.18565/aig.2019.3.10-17.
  14. Schwebke J.R., Muzny C.A., Josey W.E. Role of Gardnerella vaginalis in the pathogenesis of bacterial vaginosis: a conceptual model. J. Infect. Dis. 2014; 210(3): 338-43. https://dx.doi.org/10.1093/infdis/jiu089.
  15. Ragaliauskas T., Plečkaitytė M., Jankunec M., Labanauskas L., Baranauskiene L., Valincius G. Inerolysin and vaginolysin, the cytolysins implicated in vaginal dysbiosis, differently impair molecular integrity of phospholipid membranes. Sci. Rep. 2019; 9(1): 10606. https://dx.doi.org/10.1038/s41598-019-47043-5.
  16. Gelber S.E., Aguilar J.L., Lewis K.L., Ratner A.J. Functional and phylogenetic characterization of Vaginolysin, the humanspecific cytolysin from Gardnerella vaginalis. J. Bacteriol. 2008; 190(11): 3896-903. https://dx.doi.org/10.1128/JB.01965-07.
  17. Hardy L., Cerca N., Jespers V., Vaneechoutte M., Crucitti T. Bacterial biofilms in the vagina. Res. Microbiol. 2017; 168(9-10): 865-74. https://dx.doi.org/10.1016/j.resmic.2017.02.001.
  18. Крысанова А.А. Gardnerella vaginalis: генотипическое и фенотипическое разнообразие, факторы вирулентности и роль в патогенезе бактериального вагиноза. Журнал акушерства и женских болезней. 2019; 68(1): 59-68. [Krysanova A. A. Gardnerella vaginalis: genotypic and phenotypic diversity, virulence factors and role in the pathogenesis of bacterial vaginosis. Journal of Obstetrics and Women's Diseases. 2019; 68(1): 59-68 (in Russian)].
  19. Менухова Ю.Н. Бактериальный вагиноз: этиопатогенез, клинико-лабораторные особенности. Журнал акушерства и женских болезней. 2013; 62(4): 79-87. [Menukhova Yu.N. Bacterial vaginosis: etiopathogenesis, clinical and laboratory features. Journal of Obstetrics and Women's Diseases. 2013: 4: 79-87 (in Russian)].
  20. Lewis W.G., Robinson L.S., Gilbert N.M., Perry J.C., Lewis A.L. Degradation, foraging, and depletion of mucus sialoglycans by the vagina-adapted Actinobacterium Gardnerella vaginalis. J. Biol. Chem. 2013; 288(17): 12067-79. https://dx.doi.org/10.1074/jbc.M113.453654.
  21. Moncla B.J., Chappell C.A., Debo B.M., Meyn L.A. The effects of hormones and vaginal microflora on the glycome of the female genital tract: cervical-vaginal fluid. PLoS One. 2016; 11(7): e0158687. https://dx.doi.org/10.1371/journal.pone.0158687.
  22. Schellenberg J.J., Paramel Jayaprakash T., Withana Gamage N., Patterson M.H., Vaneechoutte M., Hill J.E. Gardnerella vaginalis subgroups defined by cpn60 sequencing and sialidase activity in isolates from Canada, Belgium and Kenya. PLoS One. 2016; 11(1): e0146510. https://dx.doi.org/10.1371/journal.pone.0146510.
  23. Березовская Е.С., Макаров И.О., Гомберг М.А., Боровкова Е.И. Биопленки при бактериальном вагинозе. Акушерство, гинекология, репродукция. 2013; 2: 34-6. [Berezovskaya E.S., Makarov I.O., Gomberg M.A., Borovkova E.I., Chulkova E.A., Arakelyan L.A. Biofilm formation at the bacterial vaginosis. Obstetrics. Gynecology. Reproduction. 2013; 2: 34-6 (in Russian)].
  24. Verstraelen H., Swidsinski A. The biofilm in bacterial vaginosis: implications for epidemiology, diagnosis and treatment: 2018 update. Curr. Opin. Infect. Dis. 2019; 32(1): 38-42. https://dx.doi.org/10.1097/QCO.0000000000000516.
  25. Swidsinski A., Loening-Baucke V., Mendling W., Dörffel Y., Schilling J., Halwani Z. et al. Infection through structured polymicrobial Gardnerella biofilms (StPM-GB). Histol. Histopathol. 2014; 29(5): 567-87. https://dx.doi.org/10.14670/HH-29.10.567.
  26. Ahmed A., Earl J., Retchless A., Hillier S.L., Rabe L.K., Cherpes T.L. et al. Comparative genomic analyses of 17 clinical isolates of Gardnerella vaginalis provide evidence of multiple genetically isolated clades consistent with subspeciation into genovars. J. Bacteriol. 2012; 194(15): 3922-37. https://dx.doi.org/10.1128/JB.00056-12.
  27. Castro J. Using an in-vitro biofilm model to assess the virulence potential of bacterial vaginosis or non-bacterial vaginosis Gardnerella vaginalis isolates. Sci. Rep. 2015; 5: 11640. https://dx.doi.org/10.1038/srep11640.
  28. Манухин И.Б., Фириченко С.В., Смирнова С.О., Оборотистова А.Н., Вученович Ю.Д. Микробиота влагалища: диагностика, влияние на здоровье женщины и коррекция нарушений. М.; 2015.103с. [Manukhin I.B., Firichenko S.V., Smirnova S.O., Oborotistova A.N., Vuchenovich Yu.D.Vaginal microbiota: diagnostics, influence on women's health and correction of disorders. M; 2015.103 p. (in Russian)].
  29. Srikantha P., Mohajeri M.H. The possible role of the microbiota-gut-brain-axis in autism spectrum disorder. Int. J. Mol. Sci. 2019; 20(9): 2115. https://dx.doi.org/10.3390/ijms20092115.
  30. Никонов Е.Л., Гуревич К.Г. Микробиота различных локусов организма. М.; 2017. 38с. [Nikonov E.L., Gurevich K.G. Microbiota of various loci of the body. Moscow; 2017. 38p. (in Russian)].
  31. Жук С.И. Состав микрофлоры кишечника и влагалища у женщин раннего репродуктивного возраста на фоне дисгормональных расстройств. В кн.: Сборник научных трудов ассоциации акушеров-гинекологов Украины. 2006: 273-6. [Zhuk S. I. Composition of intestinal and vaginal microflora in women of early reproductive age against the background of dishormonal disorders. Collection of scientific papers of the Association of Obstetricians and Gynecologists of Ukraine. 2006: 273-6. (in Russian)].
  32. Меджидова М.К., Зайдиева З.С., Вересова А.А. Микробиоценоз влагалища и факторы, влияющие на его состояние. Медицинский совет. 2013; 3(2): 118-25. [Medzhidova M.K., Zaidieva Z.S., Veresova A.A. Vaginal microbiocenosis and factors affecting its condition. Medical Council. 2013;3(2):118-25. (in Russian)].
  33. Joglekar P., Sonnenburg E.D., Higginbottom S.K., Earle K.A., Morland C., Shapiro-Ward S. et al. Genetic variation of the SusC/SusD homologs from a polysaccharide utilization locus underlies divergent fructan specificities and functional adaptation in Bacteroides thetaiotaomicron strains. mSphere. 2018; 3(3): e00185-18. https://dx.doi.org/10.1128/mSphereDirect.00185-18.
  34. Tuddenham S., Ghanem K.G., Caulfield L.E., Rovner A.J., Robinson C., Shivakoti R. et al. Associations between dietary micronutrient intake and molecular-bacterial vaginosis. Reprod. Health. 2019; 16(1): 151. https://dx.doi.org/10.1186/s12978-019-0814-6.
  35. Barrientos-Durán A., Fuentes-López A., de Salazar A., Plaza-Díaz J., García F. Reviewing the composition of vaginal microbiota: inclusion of nutrition and probiotic factors in the maintenance of eubiosis. Nutrients. 2020; 12(2): 419. https://dx.doi.org/10.3390/nu12020419.
  36. Collado M.C., Isolauri E., Laitinen K., Salminen S. Distinct composition of gut microbiota during pregnancy in overweight and normal-weight women. Am. J. Clin. Nutr. 2008; 88(4): 894‐9. https://dx.doi.org/10.1093/ajcn/88.4.894.
  37. Cani P.D., Neyrinck A.M., Fava F., Knauf C., Burcelin R.G., Tuohy K.M. et al. Selective increases of bifidobacteria in gut microflora improve high-fat-diet-induced diabetes in mice through a mechanism associated with endotoxaemia. Diabetologia. 2007; 50(11): 2374‐83. https://dx.doi.org/10.1007/s00125-007-0791-0.
  38. Ata B., Yildiz S., Turkgeldi E., Brocal V.P., Dinleyici E.C., Moya A., Urman B. The Endobiota Study: Comparison of vaginal, cervical and gut microbiota between women with stage 3/4 endometriosis and healthy controls. Sci. Rep. 2019; 9(1): 2204. https://dx.doi.org/10.1038/s41598-019-39700-6.
  39. Quaranta G., Sanguinetti M., Masucci L. Fecal microbiota transplantation: a potential tool for treatment of human female reproductive tract diseases. Front. Immunol. 2019; 10: 2653. https://dx.doi.org/10.3389/fimmu.2019.02653.
  40. Dolgushina V.F., Smol'nikova L.A., Dolgushin I.I. Factors of the local immune defence of the reproductive tract in pregnant women with vaginosis. Zh. Mikrobiol. Epidemiol. Immunobiol. 2001; (4): 89‐93.
  41. Genc M.R., Vardhana S., Delaney M.L., Onderdonk A., Tuomala R., Norwitz E., Witkin S.S.; MAP Study Group. Relationship between a toll-like receptor-4 gene polymorphism, bacterial vaginosis-related flora and vaginal cytokine responses in pregnant women. Eur. J. Obstet. Gynecol. Reprod. Biol. 2004; 116(2): 152-6. https://dx.doi.org/10.1016/j.ejogrb.2004.02.010.
  42. Taylor B.D., Darville T., Ferrell R.E., Ness R.B., Kelsey S.F., Haggerty C.L. Cross-sectional analysis of Toll-like receptor variants and bacterial vaginosis in African-American women with pelvic inflammatory disease. Sex. Transm. Infect. 2014; 90(7): 563-6. https://dx.doi.org/10.1136/sextrans-2014-051524.
  43. Goepfert A.R., Varner M., Ward K., Macpherson C., Klebanoff M., Goldenberg R.L. et al.; NICHD Maternal-Fetal Medicine Units Network. Differences in inflammatory cytokine and Toll-like receptor genes and bacterial vaginosis in pregnancy. Am. J. Obstet. Gynecol. 2005; 193(4): 1478-85. https://dx.doi.org/10.1016/j.ajog.2005.03.053. Erratum in: Am. J. Obstet. Gynecol. 2008; 199(2): e14-5.
  44. Ryckman K.K., Simhan H.N., Krohn M.A., Williams S.M. Predicting risk of bacterial vaginosis: the role of race, smoking and corticotropin-releasing hormone-related genes. Mol. Hum. Reprod. 2009; 15(2): 131-7. https://dx.doi.org/10.1093/molehr/gan081.
  45. Mirmonsef P., Gilbert D., Zariffard M.R., Hamaker B.R., Kaur A., Landay A.L., Spear G.T. The effects of commensal bacteria on innate immune responses in the female genital tract. Am. J. Reprod. Immunol. 2011; 65(3): 190-5. https://dx.doi.org/10.1111/j.1600-0897.2010.00943.x.
  46. Hay P. Bacterial vaginosis. 2014; 42(7): 359-63.
  47. Бурменская О.В., Байрамова Г.Р., Непша О.С., Трофимов Д.Ю., Муравьева В.В., Абакарова П.Р., Стрельченко Д.А., Кряжева В.С., Сухих Г.Т. Видовой состав лактобактерий при неспецифических вагинитах и бактериальном вагинозе и его влияние на локальный иммунитет. Акушерство и гинекология 2014; 1: 41-5. [Burmenskaya O.V., Bairamova G.R., Nepsha O.S., Trofimov D.Y., Muravieva V.V., Abakarova P.R., Strelchenko D.A., Kryazheva V.S., Sukhikh G.T. The specific composition of lactobacilli in non-specific vaginitis and bacterial vaginosis and its effect on local immunity. Obstetrics and Gynecology 2014; 1:41-5. (in Russian)].
  48. Fichorova R.N., Buck O.R., Yamamoto H.S., Fashemi T., Dawood H.Y., Fashemi B. et al. The villain team-up or how Trichomonas vaginalis and bacterial vaginosis alter innate immunity in concert. Sex. Transm. Infect. 2013; 89(6): 60-6. https://dx.doi.org/10.1136/sextrans-2013-051052.
  49. Thurman A.R., Kimble T., Herold B., Mesquita P.M., Fichorova R.N., Dawood H.Y. et al. Bacterial vaginosis and subclinical markers of genital tract inflammation and mucosal immunity. AIDS Res. Hum. Retroviruses. 2015; 31(11): 1139-52. https://dx.doi.org/10.1089/aid.2015.0006.
  50. Witkin S.S., Linhares I.M., Giraldo P., Ledger W.J. An altered immunity hypothesis for the development of symptomatic bacterial vaginosis. Clin. Infect. Dis. 2007; 44(4): 554-7. https://dx.doi.org/10.1086/511045.
  51. Припутневич Т.В., Мелкумян А.Р., Анкирская А.С., Трофимов Д.Ю., Муравьева В.В., Завьялова М.Г. Использование современных лабораторных технологий в видовой идентификации лактобактерий при оценке состояния микробиоты влагалища у женщин репродуктивного возраста. Акушерство и гинекология. 2013; 1: 76-80. [Priputnevich T.V., Melkumyan A.R., Ankirskaya A.S., Trofimov D.Yu., Muravyova V.V., Zavyalova M.G. The use of modern laboratory technologies in the species identification of lactobacilli in assessing the state of the vaginal microbiota in women of reproductive age. Obstetrics and Gynecology, 2013; 1: 76-80. (in Russian)].

Received 20.02.2021

Accepted 10.06.2021

About the Authors

Ada T. Uruymagova, postgraduate student of the Department of Obstetrics, Gynecology, Perinatology and Reproductology, Academician V.I. Kulakov National Medical Research Center for Obseters, Gynecology and Perinatology, Ministry of Health of Russia, ada.uruimagova@yandex.ru, 117997, Russia, Moscow, Academician Oparin str., 4.
Vera N. Prilepskaya, Dr. Med. Sci., Professor, Honored Scientist of the Russian Federation, Head of the Outpatient Department, Academician V.I. Kulakov National Medical Research Center for Obseters, Gynecology and Perinatology, Ministry of Health of Russia, vprilepskaya@mail.ru, 117997, Russia, Moscow, Academician Oparin str., 4.
Elena A. Mezhevitinova, PhD, Leading Researcher of the Outpatient Department, Academician V.I. Kulakov National Medical Research Center for Obseters, Gynecology
and Perinatology, Ministry of Health of Russia, mejevitinova@mail.ru, 117997, Russia, Moscow, Academician Oparin str., 4.
Andrey E. Donnikov, PhD, Head of the Laboratory of Molecular Genetic Methods, Academician V.I. Kulakov National Medical Research Center for Obseters, Gynecology
and Perinatology, Ministry of Health of Russia, donnikov@dna-technology.ru, 117997, Russia, Moscow, Academician Oparin str., 4.
Jamilya I. Attoeva, postgraduate student of the Department of Obstetrics, Gynecology, Perinatology and Reproductology, Academician V.I. Kulakov National Medical Research Center for Obseters, Gynecology and Perinatology, Ministry of Health of Russia, attoevadjamilya@gmail.com, 117997, Russia, Moscow, Academician Oparin str., 4

Authors’ contributions: Uruimagova A.T., Prilepskaya V.N., Mezhevitinova E.A., Donnikov A.E., Attoeva D.I. – development of the design of the investigation; obtaining data for analysis; review of publications on the topic of the article; analysis of the findings; writing the text of the manuscript.
Conflicts of interest: The authors declare that there are no conflicts of interest.
Funding: The investigation has not been sponsored.

For citation: Uruimagova A.T., Prilepskaya V.N., Mezhevitinova E.A., Donnikov A.E., Attoeva D.I. Dysbiotic disorders and innate immunity indices in bacterial vaginosis.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2021; 9: 28-35 (in Russian)

Similar Articles

By continuing to use our site, you consent to the processing of cookies that ensure the proper functioning of the site.