The role of Lactobacillus iners and bacterial vaginosis-associated microorganisms in making up the vaginal microbiota

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Abstract

Objective: To summarize the data available in the literature on the currently used criteria for evaluating the vaginal microbiota in reproductive-aged women, the principles of its classification, and the exogenous and endogenous factors influencing the microbial structure. The review includes data from the publications presented in the MedLine and Russian Science Citation databases. The review describes the key distinguishing features of the species Lactobacillus iners from other vaginal lactobacillus species, including cultivation features, tinctorial properties, and pathogenicity power. It presents data on the frequency of this species in the microbiota of reproductive-aged women and elucidates the need for its isolation and identification in the microbiological laboratories of any level in order to make a correct diagnosis. There are data on the characteristics of the vaginal microbiota in bacterial vaginosis, which are due to a variety of the microflora, including the species diversity of Gardnerella spp. The review highlights the role of a polymicrobial biofilm in the pathogenesis of bacterial vaginosis. It touches upon the relevance of a further study of the interaction of Gardnerella spp. and L. iners species, as well as the effectiveness of an integrated approach to evaluating the vaginal microbiota, by using the results of classical and molecular biological methods. Conclusion: L. iners is one of the most common lactobacilli in the microbiota of reproductive-aged women. The role of this species in the functional stability of the vaginal microbiota has not yet been def ined to date. Further investigation of the species is required to establish strain diversity. There is a need for routine practice introduction of research methods allowing the isolation of L. iners in the microbiological laboratories of all levels.

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About the authors

Natalya V. Mikhanoshina

Academician V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: mikhanoshina.natalya@yandex.ru
bacteriologist, Head of Biomaterials Collection and Storage Laboratory, Institute of Microbiology, Antimicrobial Therapy and Epidemiology

Tatiana V. Priputnevich

Academician V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: priputl@gmail.com
Corresponding Member of the RAS, Dr. Med. Sci., Director of the Institute of Microbiology, Antimicrobial Therapy and Epidemiology

Guldana R. Bairamova

Academician V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: bayramova@mail.ru
Dr. Med. Sci., Professor at the Department of Obstetrics and Gynecology of the Department of Professional Education, Head of Clinical Work of the Scientific Polyclinic Department

References

  1. Ravel J., Gajer P., Abdo Z., Schneider G.M., Koenig S.S.K., McCulle S.L. et al. Vaginal microbiome of reproductive-age women. Proc. Natl. Acad. Sci. USA. 2011; 108(Suppl. 1): 4680-7. https://dx.doi.org/10.1073/pnas.1002611107.
  2. Fettweis J.M., Brooks J.P., Serrano M.G., Sheth N.U., Girerd PH., Edwards D.J. et al. Differences in vaginal microbiome in African American women versus women of European ancestry. Microbiology (Reading). 2014; 160(Pt 10): 227282. https://dx.doi.org/10.1099/mic.0.081034-0.
  3. Forsythe P., Kunze W.A. Voices from within: gut microbes and the CNS. Cell. Mol. Life Sci. 2013; 70(1): 55-69. https://dx.doi.org/10.1007/s00018-012-1028-z.
  4. Frank D.N., Pace N.R. Gastrointestinal microbiology enters the metagenomics era. Curr. Opin. Gastroenterol. 2008; 24(1): 4-10. https://dx.doi.org/10.1097/MOG.0b013e3282f2b0e8.
  5. Noyes N., Cho K.-C., Ravel J., Forney L.J., Abdo Z. Associations between sexual habits, menstrual hygiene practices, demographics and the vaginal microbiome as revealed by Bayesian network analysis. PLoS One. 2018; 13(1): e0191625. https://dx.doi.org/10.1371/journal.pone.0191625.
  6. Schwebke J.R. Diagnostic methods for bacterial vaginosis. Int. J. Gynaecol. Obstet. 1999; 67(Suppl. 1): S21-3. https://dx.doi.org/10.1016/s0020-7292(99)00134-4.
  7. Culhane J.F., Rauh V., McCollum K.F., Elo I.T., Hogan V. Exposure to chronic stress and ethnic differences in rates of bacterial vaginosis among pregnant women. Am. J. Obstet. Gynecol. 2002; 187(5): 1272-6. https://dx.doi.org/10.1067/mob.2002.127311.
  8. Gupta S. Microbiome: Puppy power. Nature. 2017; 543(7647): S48-9. https://dx.doi.org/10.1038/543S48a.
  9. 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. https://dx.doi.org/10.1186/s12934-020-01464-4.
  10. Krog M.C., Madsen M.E., Bliddal S., Bashir Z., Vex0 L.E., Hartwell D. et al. The microbiome in reproductive health: protocol for a systems biology approach using a prospective, observational study design. Hum. Reprod. Open. 2022; 2022(2): hoac015. https://dx.doi.org/10.1093/hropen/hoac015.
  11. Wit kin 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.
  12. Witkin S.S., Linhares I.M. Why do lactobacilli dominate the human vaginal microbiota? BJOG. 2017; 124(4): 606-11. https://dx.doi.org/10.1111/1471-0528.14390.
  13. Boskey E.R., Cone R.A., Whaley K.J., Moench T.R. Origins of vaginal acidity: high D/L lactate ratio is consistent with bacteria being the primary source. Hum. Reprod. 2001; 16(9): 1809-13. https://dx.doi.org/10.1093/humrep/16.9.1809.
  14. Pararas M.V., Skevaki C.L., Kafetzis D.A. Preterm birth due to maternal infection: Causative pathogens and modes of prevention. Eur. J. Clin. Microbiol. Infect. Dis. 2006; 25(9): 562-9. https://dx.doi.org/10.1007/s10096-006-0190-3.
  15. Atassi F., Servin A.L. Individual and co-operative roles of lactic acid and hydrogen peroxide in the killing activity of enteric strain Lactobacillus johnsonii NCC933 and vaginal strain Lactobacillus gasseri KS120.1 against enteric, uropathogenic and vaginosis-associated patho. FEMS Microbiol. Lett. 2010; 304(1): 29-38. https://dx.doi.org/10.1111/j.1574-6968.2009.01887.x.
  16. O’Hanlon D.E., Moench T.R., Cone R.A. In vaginal fluid, bacteria associated with bacterial vaginosis can be suppressed with lactic acid but not hydrogen peroxide. BMC Infect. Dis. 2011; 11: 200. https://dx.doi.org/10.1186/1471-2334-11-200.
  17. Stoyancheva G., Marzotto M., Dellaglio F., Torriani S. Bacteriocin production and gene sequencing analysis from vaginal Lactobacillus strains. Arch. Microbiol. 2014; 196(9): 645-53. https://dx.doi.org/10.1007/s00203-014-1003-1.
  18. Neeser J.R., Gran at o D., Rouvet M., Servin A., Teneberg S., Karlsson K.A. Lactobacillus johnsonii La1 shares carbohydrate-binding specificities with several enteropathogenic bacteria. Glycobiology. 2000; 10(11): 1193-9. https://dx.doi.org/10.1093/glycob/10.11.1193.
  19. Zarate G., Nader-Macias M.E. Influence of probiotic vaginal lactobacilli on in vitro adhesion of urogenital pathogens to vaginal epithelial cells. Lett. Appl. Microbiol. 2006; 43(2): 174-80. https://dx.doi.org/10.1111/j.1472-765X.2006.01934.x.
  20. Ribet D., Cossart P. How bacterial pathogens colonize their hosts and invade deeper tissues. Microbes Infect. 2015; 17(3): 173-83. https://dx.doi.org/10.1016/j.micinf.2015.01.004.
  21. Petrova M.I., Lievens E., Malik S., Imholz N., Lebeer S. Lactobacillus species as biomarkers and agents that can promote various aspects of vaginal health. Front. Physiol. 2015; 6: 81. https://dx.doi.org/10.3389/fphys.2015.00081.
  22. Pekmezovic M., Mogavero S., Naglik J.R., Hube B. Host-pathogen interactions during female genital tract infections. Trends Microbiol. 2019; 27(12): 982-96. https://dx.doi.org/10.1016/j.tim.2019.07.006.
  23. Uchihashi M., Bergin I.L., Bassis C.M., Hashway S.A., Chai D., Bell J.D. Influence of age, reproductive cycling status, and menstruation on the vaginal microbiome in baboons (Papio anubis). Am. J. Primatol. 2015; 77(5): 563-78. https://dx.doi.org/10.1002/ajp.22378.
  24. Ma W., Mishra S., Gajanayaka N., Angel J.B., Kumar A. HIV-1 Nef inhibits lipopolysaccharide-induced IL-12p40 expression by inhibiting JNK-activated NFkB in human monocytic cells. J. Biol. Chem. 2012; 287(1): 804. https://dx.doi.org/10.1074/jbc.A111.710013.
  25. Dethlefsen L., Huse S., Sogin M.L., Relman D.A. The pervasive effects of an antibiotic on the human gut microbiota, as revealed by deep 16S rRNA sequencing. PLoS Biol. 2008; 6(11): e280. https://dx.doi.org/10.1371/journal.pbio.0060280.
  26. Manichanh C., Rigottier-Gois L., Bonnaud E., Gloux K., Pelletier E., Frangeul L. et al. Reduced diversity of faecal microbiota in Crohn’s disease revealed by a metagenomic approach. Gut. 2006; 55(2): 205-11. https://dx.doi.org/10.1136/gut.2005.073817.
  27. Fredricks D.N., Fiedler T.L., Marrazzo J.M. Molecular identification of bacteria associated with bacterial vaginosis. N. Engl. J. Med. 2005; 353(18): 1899-911. https://dx.doi.org/10.1056/NEJMoa043802.
  28. 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. https://dx.doi.org/10.1016/j.micpath.2018.11.046.
  29. Peebles K., Velloza J., Balkus J.E., McClelland R.S., Barnabas R.V. High global burden and costs of bacterial vaginosis: A systematic review and metaanalysis. Sex. Transm. Dis. 2019; 46(5): 304-11. https://dx.doi.org/10.1097/OLQ.0000000000000972.
  30. Мелкумян А.Р. Припутневич Т.В. Влагалищные лактобактерии - современные подходы к видовой идентификации и изучению их роли в микробном сообществе. Акушерство и гинекология. 2013; 7: 18-23.
  31. Ворошилина Е.С., Зорников Д.Л., Плотко Е.Э. Нормальное состояние микробиоценоза влагалища: оценка с субъективной, экспертной и лабораторной точек зрения. Вестник Российского государственного медицинского университета. 2017; 2: 42-7.
  32. Falsen E., Pascual C., Sjoden B., Ohlen M., Collins M.D. Phenotypic and phylogenetic characterization of a novel Lactobacillus species from human sources: description of Lactobacillus iners sp. nov. Int. J. Syst. Bacteriol. 1999; 49(Pt 1): 217-21. https://dx.doi.org/10.1099/00207713-49-1-217.
  33. Lebeer S., Vanderleyden J., De Keersmaecker S.C.J. Genes and molecules of lactobacilli supporting probiotic action. Microbiol. Mol. Biol. Rev. 2008; 72(4): 728-64, Table of Contents. https://dx.doi.org/10.1128/MMBR.00017-08.
  34. Yoshimura K., Ogawa M., Saito M. In vitro characteristics of intravaginal Lactobacilli; why is L. iners detected in abnormal vaginal microbial flora? Arch. Gynecol. Obstet. 2020; 302(3): 671-7. https://dx.doi.org/10.1007/s00404-020-05634-y.
  35. Kim H., Kim T., Kang J., Kim Y., Kim H. Is Lactobacillus gram-positive? A case study of Lactobacillus iners. Microorganisms. 2020; 8(7): 969. https://dx.doi.org/10.3390/microorganisms8070969.
  36. Vaneechoutte M. Lactobacillus iners, the unusual suspect. Res. Microbiol. 2017; 168(9-10): 826-36.
  37. Klebanoff M.A., Schwebke J.R., Zhang J., Nansel T.R., Yu K.-F., Andrews W.W. Vulvovaginal symptoms in women with bacterial vaginosis. Obstet. Gynecol. 2004; 104(2): 267-72. https://dx.doi.org/10.1016/j.resmic.2017.09.003.
  38. Ragaliauskas T., Pleckaityte 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.
  39. Amabebe E., Anumba D.O.C. The vaginal microenvironment: the physiologic role of Lactobacilli. Front. Med. (Lausanne). 2018; 5: 181. https://dx.doi.org/10.3389/fmed.2018.00181.
  40. Будиловская О.В. Современные представления о лактобациллах влагалища женщин репродуктивного возраста. Журнал акушерства и женских болезней. 2016; 96(4): 34-43.
  41. Macklaim J.M., Gloor G.B., Anukam K.C., Cribby S., Reid G. At the crossroads of vaginal health and disease, the genome sequence of Lactobacillus iners AB-1. Proc. Natl. Acad. Sci. USA. 2011; 108(Suppl. 1): 4688-95. https://dx.doi.org/10.1073/pnas.1000086107.
  42. Nilsen T., Swedek I., Lagenaur L.A., Parks T.P. Novel selective inhibition of Lactobacillus iners by Lactobacillus-derived bacteriocins. Appl. Environ. Microbiol. 2020; 86(20): e01594-20. https://dx.doi.org/10.1128/AEM.01594-20.
  43. Bretelle F., Rozenberg P., Pascal A., Favre R., Bohec C., Loundou A. et al. High Atopobium vaginae and Gardnerella vaginalis vaginal loads are associated with preterm birth. Clin. Infect. Dis. 2015; 60(6): 860-7. https://dx.doi.org/10.1093/cid/ciu966.
  44. Piot P., van Dyck E., Goodfellow M., Falkow S. A taxonomic study of Gardnerella vaginalis (Haemophilus vaginalis) Gardner and Dukes 1955. J. Gen. Microbiol. 1980; 119(2): 373-96. https://dx.doi.org/10.1099/00221287-119-2-373.
  45. Rosca A.S., Castro J., Sousa L.G.V., Cerca N. Gardnerella and vaginal health: the truth is out there. FEMS Microbiol. Rev. 2020; 44(1): 73-105. https://dx.doi.org/10.1093/femsre/fuz027.
  46. Gonzalez Pedraza Aviles A., Ortiz Zaragoza M.C., Irigoyen Coria A. Bacterial vaginosis a “broad overview”. Rev. Latinoam. Microbiol. 1999; 41(1): 25-34.
  47. Zozaya-Hinchliffe M., Lillis R., Martin D.H., Ferris M.J. Quantitative PCR assessments of bacterial species in women with and without bacterial vaginosis. J. Clin. Microbiol. 2010; 48(5): 1812-9. https://dx.doi.org/10.1128/JCM.00851-09.
  48. Vaneechoutte M., Guschin A., Van Simaey L., Gansemans Y., Van Nieuwerburgh F., Cools P. 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. https://dx.doi.org/10.1099/ijsem.0.003200.
  49. Castro J., Rosca A.S., Cools P., Vaneechoutte M., Cerca N. Gardnerella vaginalis enhances Atopobium vaginae viability in an in vitro model. Front. Cell. Infect. Microbiol. 2020; 10: 83. https://dx.doi.org/10.3389/fcimb.2020.00083.
  50. Macklaim J.M., Fernandes A.D., Di Bella J.M., Hammond J.-A., Reid G., Gloor G.B. Comparative meta-RNA-seq of the vaginal microbiota and differential expression by Lactobacillus iners in health and dysbiosis. Microbiome. 2013; 1(1): 12. https://dx.doi.org/10.1186/2049-2618-1-12.

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