Current views on vaginal microbiota and its impact on pregnancy outcomes

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Abstract


Vaginal dysbiosis is one of the leading causes of adverse pregnancy outcomes. The main role in maintaining the constancy of vaginal microbiocenosis belongs to lactobacilli. The infection process can be caused by both pathogenic and opportunistic microorganism, however, in the vast majority of cases vaginal infections is associated with the normal microflora. Violation of microbiocenosis of the vagina in combination with a cervical barrier failure leads to migration of bacteria in the amniotic cavity and the launch of the pathological mechanisms leading to pregnancy loss. The paper presents current data on the influence of vaginal infection on pregnancy loss. Consider the ability of Lactobacillus iners predispose to the development of pathological vaginal microflora. Attention was paid to the basic approaches to prevention and treatment of dysbiotic disorders. Discussion on the use of bacteriophages in obstetrics and gynecology.


Anna A. Siniakova

Author for correspondence.
annakizeeva@yandex.ru
Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott
Russian Federation, St. Petersburg

post-graduate student

  • Garland SM, Ní Chuileannáin F, Satzke C, Robins-Browne R. Mechanisms and markers of infection in pregnancy. J Reprod Immunol. 2002;57(1-2):169-83. doi: 10.1016/S0165-0378(02)00018-9.
  • Янковский Д.С., Дымент Г.С. Использование пробиотиков с целью улучшения репродуктивного здоровья женщины // Здоровье женщины. – 2008. – № 2. – С. 161–170. [Yankovskii DS, Dyment GS. Ispol’zovanie probiotikov s tsel’yu uluchsheniya reproduktivnogo zdorov’ya zhenshchiny. Zdorov’e zhenshchiny. 2008;(2):161-70. (In Russ.)]
  • Кира Е.Ф., Берлев И.В., Молчанов О.Л. Особенности течения беременности, родов и послеродового периода у женщин с дисбиотическими нарушениями влагалища // Журнал акушерства и женских болезней. – 1999. – № 2. – С. 8–11. [Kira EF, Berlev IV, Molchanov OL. Osobennosti techeniya beremennosti, rodov i poslerodovogo perioda u zhenshchin s disbioticheskimi narusheniyami vlagalishcha. Journal of Obstetrics and Women’s Diseases. 1999;(2):8-11. (In Russ.)]
  • Савичева А.М., Башмакова М.А., Красносельских Т.В., и др. Лабораторная диагностика бактериального вагиноза: методические рекомендации. – СПб.: Изд-во Н-Л, 2011. – 28 с. [Savicheva AM, Bashmakova MA, Krasnosel’skikh TV, et al. Laboratornaya diagnostika bakterial’nogo vaginoza: metodicheskie rekomendatsii. Saint Petersburg: Izd-vo N-L; 2011. 28 p. (In Russ.)]
  • O’Hanlon DE, Moench TR, Cone RA. Vaginal pH and microbicidal lactic acid when lactobacilli dominate the microbiota. PLoS One. 2013;8(11):e80074. doi: 10.1371/journal.pone.0080074.
  • Witkin SS, Alvi S, Bongiovanni AM, et al. Lactic acid stimulates interleukin-23 production by peripheral blood mononuclear cells exposed to bacterial lipopolysaccharide. FEMS Immunol Med Microbiol. 2011;61(2):153-8. doi: 10.1111/j.1574-695X.2010.00757.x.
  • Zodzika J, Rezeberga D, Jermakova I, et al. Factors related to elevated vaginal pH in the first trimester of pregnancy. Acta Obstet Gynecol Scand. 2011;90(1):41-6. doi: 10.1111/j.1600-0412.2010.01011.x.
  • Human Microbiome Project Consortium. Structure, function and diversity of the healthy human microbiome. Nature. 2012;486(7402):207-14. doi: 10.1038/nature11234.
  • Pavlova SI, Kilic AO, So JS, et al. Genetic diversity of vaginal lactobacilli from women in different countries on 16S rRNA gene sequences. J Appl Microbiol. 2002;92(3):451-9. doi: 10.1046/j.1365-2672.2002.01547.x.
  • Giakoumelou S, Wheelhouse N, Cuschieri K, et al. The role of infection in miscarriage. Hum Reprod Update. 2016;22(1):116-33. doi: 10.1093/humupd/dmv041.
  • Wilks M, Wiggins R, Whiley A, et al. Identification and H2O2 production of vaginal lactobacilli from pregnant women at high risk of preterm birth and relation with outcome. J Clin Microbiol. 2004;42:713-7. doi: 10.1128/JCM.42.2.713-717.2004.
  • Song Y, Kato N, Matsumiya Y, et al. Identification of and hydrogen peroxide production by fecal and vaginal lactobacilli isolated from Japanese women and newborn infants. J Clin Microbiol. 1999;37:3062-4.
  • Falsen E, Pascual C, Sjoden B, et al. Phenotypic and phylogenetic characterization of a novel Lactobacillus species from human sources: description of Lactobacillus iner ssp. nov. Int J Syst Bacteriol. 1999;49:217-21. doi: 10.1099/00207713-49-1-217.
  • Vásquez A, Jakobsson T, Ahrné S, et al. Vaginal Lactobacillus Flora of Healthy Swedish Women. J Clin Microbiol. 2002;40(8):2746-2749. doi: 10.1128/JCM.40.8.2746-2749.2002.
  • Donders GG, Van Calsteren K, Bellen G, et al. 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. doi: 10.1111/j.1471-0528.2009.02237.x.
  • Macklaim JM, Gloor GB, Anukam KC, et al. At the crossroads of vaginal health and disease, the genome sequence of Lactobacillus iners AB-1. Proc Natl Acad Sci USA. 2011;108(1):4688-95. doi: 10.1073/pnas.1000086107.
  • Ravel J, Gajer P, Abdo Z, et al. Vaginal microbiome of reproductive-age women. Proc Natl Acad Sci USA. 2011;108:4680-7. doi: 10.1073/pnas.1002611107.
  • Witkin SS, Mendes-Soares H, Linhares, et al. 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;4e00460-e00413. doi: 10.1128/mBio.00460-13.
  • Rampersaud R, Planet PJ, Randis TM, et al. Inerolysin, a cholesterol-dependent cytolysin produced by Lactobacillus iners. J Bacteriol. 2011;193(5):1034-41. doi: 10.1128/JB.00694-10.
  • Petricevic L, Domig K, Nierscher FJ, et al. Characterisation of the vaginal Lactobacillus microbiota associated with preterm delivery. Sci Rep. 2014;4:51362. doi: 10.1038/srep05136.
  • Ravel J, Gajer P, Abdo Z, et al. Vaginal microbiome of reproductive-age women. Proc Natl Acad Sci USA. 2011;108:S4680-S7. doi: 10.1073/pnas.1002611107.
  • Witkin SS, Linhares IM, Bongiovanni AM, Herway C, et al. Unique alterations in infection-induced immune activation during pregnancy. BJOG. 2011;118(2):145-53. doi: 10.1111/j.1471-0528.2010.02773.x.
  • Romero R, Hassan SS, Gajer P, et al. The composition and stability of the vaginal microbiota of normal pregnant women is different from that of non-pregnant women. Microbiome. 2014;2(1):10. doi: 10.1186/2049-2618-2-10.
  • Lamont RF, Taylor-Robinson D. The role of bacterial vaginosis, aerobic vaginitis, abnormal vaginal flora and the risk of preterm birth. BJOG. 2010;117(1):119-20. doi: 10.1111/j.1471-0528.2009.02403.x.
  • Donders GG, Vereecken A, Bosmans E, et al. Definition of a type of abnormal vaginal flora that is distinct from bacterial vaginosis: aerobic vaginitis. BLOG. 2002;109:34-43. doi: 10.1111/j.1471-0528.2002.00432.x.
  • Donders G, Bellen G, Rezeberga D. Aerobic vaginitis in pregnancy. BJOG. 2011Sep;118(10):1163-70. doi: 10.1111/j.1471-0528.2011.03020.x.
  • Leitich H, Kiss H. Asymptomatic bacterial vaginosis and intermediate flora as risk factors for adverse pregnancy outcome. Best Pract Res Clin Obstet Gynaecol. 2007;21:375-90. doi: 10.1016/j.bpobgyn.2006.12.005.
  • Lamont RF, Sobel JD, Akins RA, et al. The vaginal microbiome: new information about genital tract flora using molecular based techniques. BJOG. 2011;118:533-49. doi: 10.1111/j.1471-0528.2010.02840.x.
  • Holst RM, Jacobsson B, Hagberg H, Wennerholm UB. Cervical length in women in preterm labor with intact membranes: relationship to intra-amniotic inflammation/microbial invasion, cervical inflammation and preterm delivery. Ultrasound Obstet Gynecol. 2006;28:768-74. doi: 10.1002/uog.3837.
  • Jacobsson B, Pernevi P, Chidekel L, Jorgen Platz-Christensen J. Bacterial vaginosis in early pregnancy may predispose for preterm birth and postpartum endometritis. Acta Obstet Gynecol Scand. 2002;81:1006-10. doi: 10.1034/j.1600-0412.2002.811103.x.
  • Laxmi U, Agrawal S, Raghunandan C, et al. Association of bacterial vaginosis with adverse fetomaternal outcome in women with spontaneous preterm labor: a prospective cohort study. J Matern Fetal Neonatal Med. 2012;25(1):64-7. doi: 10.3109/14767058.2011.565390.
  • Kenyon C, Colebunders R, Crucitti T. The global epidemiology of bacterial vaginosis: a systematic review. Am J Obstet Gynecol. 2013;209(6):505-23. doi: 10.1016/j.ajog.2013.05.006.
  • Oakeshott P, Hay P, Hay S, et al. Association between bacterial vaginosis or chlamydial infection and miscarriage before 16 weeks’ gestation: prospective community based cohort study. Br Med J. 2002;325:1334-8.
  • Menard JP, Fenollar F, Henry M, et al. Molecular quantification of Gardnerella vaginalis and Atopobium vaginae loads to predict bacterial vaginosis. Clin Infect Dis. 2008;47:33-43. doi: 10.1086/588661.
  • Romanik M, Wojciechowska-Wieja A, Martirosian G. Aerobic vaginitis-diagnostic problems and treatment. Ginekol Pol. 2007;78(6):488-91.
  • Donders GG, Vereecken А, Bosnians Е, et al. Aerobic vaginitis is an entity with abnormal vaginal flora that is distinct from bacterial vaginosis. Int J STD AIDS. 2001;12(2):68.
  • Reid G, Bocking A. The potential for probiotics to prevent bacterial vaginosis and preterm labor. Am J Obstet Gynecol. 2003;189(4):1202-8. doi: 10.1067/S0002-9378(03)00495-2.
  • Curzik D, Drazancic А. Nonspecific aerobic vaginitis and pregnancy. Fetal Diagn Ther. 2001;16(3):87-192. doi: 10.1159/000053906.
  • Amsel R, Totten PA, Spiegel CA, et al. Nonspecific vaginitis. Diagnostic criteria and microbial and epidemiologic associations. Am J Med. 1983;74:14-22. doi: 10.1016/0002-9343(83)91112-9.
  • Nugent RP, Krohn MA, Hillier SL. Reliability of diagnosing bacterial vaginosis is improved by a standardized method of gram stain interpretation. J Clin Microbiol. 1991;29:297-301.
  • Donders GG, Van Calsteren K, Bellen G, et al. 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. doi: 10.1111/j.1471-0528.2009.02237.x.
  • Meis PJ, Goldenberg RL, Mercer B, Moawad A. The preterm prediction study: Significance of vaginal infections. Am J Obstet Gynecol. 1995;173:1231-5. doi: 10.1016/0002-9378(95)91360-2.
  • Nygren P, Fu R, Freeman M, et al. Evidence on the benefits and harms of screening and treating pregnant women who are asymptomatic for bacterial vaginosis: an update review for the U.S. Preventive Services Task Force. Ann Intern Med. 2008;148:220-33. doi: 10.7326/0003-4819-148-3-200802050-00008.
  • Brocklehurst P, Gordon A, Heatley E, Milan SJ. Antibiotics for treating bacterial vaginosis in pregnancy. Cochrane Database Syst Rev. 2013;(1):CD000262. doi: 10.1002/14651858.CD000262.pub4.
  • Lamont RF, Nhan-Chang CL, Sobel JD, et al. Treatment of abnormal vaginal flora in early pregnancy with clindamycin for the prevention of spontaneous preterm birth: a systematic review and metaanalysis. Am J Obstet Gynecol. 2011;205:177-90. doi: 10.1016/j.ajog.2011.03.047.
  • Lamont RF, Duncan SL, Mandal D, Basset P. Intra vaginal clindamycin to reduce preterm birth in women with abnormal genital tract flora. Obstet Gynecol. 2003;101:516-22. doi: 10.1016/S0029-7844(02)03054-5.
  • Tansarli GS, Kostaras EK, Athanasiou S, Falagas ME. Prevalence and treatment of aerobic vaginitis among non-pregnant women: evaluation of the evidence for an underestimated clinical entity. Eur J Clin Microbiol Infect Dis. 2013;32(8):977-84. doi: 10.1007/s10096-013-1846-4.
  • Fan A, Yue Y, Geng N, et al. Aerobic vaginitis and mixed infections: comparison of clinical and laboratory findings. Arch Gynecol Obstet. 2013;287(2):329-35. doi: 10.1007/s00404-012-2571-4.
  • Gondo F, da Silva MG, Polettini J, et al. Vaginal flora alterations and clinical symptoms in low-risk pregnant women. Gynecol Obstet Invest. 2011;71(3):158-62. doi: 10.1159/000316051.
  • King AE, Paltoo A, Kelly RW, et al. Expression of natural antimicrobials by human placenta and fetal membranes. Placenta. 2007;28(2-3):161-9. doi: 10.1016/j.placenta.2006.01.006.
  • Zodzika J, Jermakowa I, Rezeberga D, et al. Factors related to elelvated vaginal pH in the first trimester of pregnancy. Acta Obstet Gynecol Scand. 2011;90(1):41-6. doi: 10.1111/j.1600-0412.2010.01011.x.
  • Карапетян Т.Э., Муравьева В.В., Анкирская А.С. Аэробные вагиниты и беременность // Акушерство и гинекология. – 2013. – № 4. – С. 25–28. [Karapetyan TE, Muravyeva VV, Ankirskaya AS. Aerobic vaginitis and pregnancy. Obstetrics and Gynecology. 2013;(4):25-8. (In Russ.)]
  • Федеральные клинические рекомендации по ведению больных бактериальным вагинозом. – М.: Российское общество дерматовенерологов и косметологов, 2015. Доступно по: http://www.cnikvi.ru/docs/clinic_recs/infektsii-peredavaemye-polovym-putem. [Federal’nye klinicheskie rekomendatsii po vedeniyu bol’nykh bakterial’nym vaginozom. Moscow: Rossiiskoe obshchestvo dermatovenerologov i kosmetologov; 2015. Available at: http://www.cnikvi.ru/docs/clinic_recs/infektsii-peredavaemye-polovym-putem. (In Russ.)]
  • Workowski KA, Berman S. Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2010. MMWR Recomm Rep. 2010;59(RR-12):1-110.
  • De Backer E, Verhelst R, Verstraelen H, et al. Antibiotic susceptibility of Atopobium vaginae. BMC Infect Dis. 2006;6:51. doi: 10.1186/1471-2334-6-51.
  • Bahar H, Torun MM, Oçer F, et al. Mobiluncus species in gynaecological and obstetric infections: antimicrobial resistance and prevalence in a Turkish population. Int J Antimicrob Agents. 2005;25(3):268-71. doi: 10.1016/j.ijantimicag.2004.09.019.
  • Togni G, Battini V, Bulgheroni A, et al. In vitro activity of nifuratel on vaginal bacteria: could it be a good candidate for the treatment of bacterial vaginosis? Anti microb Agents Chemother. 2011;55(5):2490-2. doi: 10.1128/AAC.01623-10.
  • Ugwumadu A, Manyonda I, Reid F, Hay P. Effect of early oral clindamycin on late miscarriage and preterm delivery in asymptomatic women with abnormal vaginal flora and bacterial vaginosis: a randomised controlled trial. Lancet. 2003;361:983-8. doi: 10.1016/S0140-6736(03)12823-1.
  • Tempera G, Furneri PM. Management of aerobic vaginitis. Gynecol Obstet Invest. 2010;70(4):244-9. doi: 10.1159/000314013.
  • Han C, Wu W, Fan A, et al. Diagnostic and therapeutic advancements for aerobic vaginitis. Arch Gynecol Obstet. 2015;291(2):251-7. doi: 10.1007/s00404-014-3525-9.
  • Donders GG, Ruban K, Bellen G. Selecting anti-microbial treatment of aerobic vaginitis. Curr Infect Dis Rep. 2015;17(5):477. doi: 10.1007/s11908-015-0477-6.
  • Nagaraja P. Antibiotic resistance of Gardnerella vaginalis in recurrent bacterial vaginosis. Indian J Med Microbiol. 2008;26(2):155-7. doi: 10.4103/0255-0857.40531.
  • Swidsinki A, Mendling W, Loening-Baucke V, et al. An adherent Gardnerella vaginalis biofilm persists on the vaginal epithelium after standard therapy with metronidazole. Am J Obstet Gynecol, 2008;198:97.e1-6. doi: 10.1016/j.ajog.2007.06.039.
  • McMillan A, Dell M, Zellar MP G, et al. Disruption of urogenital biofilms by lactobacilli. Colloids Surf B Biointerfaces. 2011;86(1):58-64. doi: 10.1016/j.colsurfb.2011.03.016.
  • Parent D, Bossens M, Bayot D, et al. Therapy of bacterial vaginosis using exogenously-applied Lactobacilli acidophili and a low dose of estriol: a placebo-controlled multicentric clinical trial. Arzneimittelforschung. 1996;46:68-73.
  • Anukam KC, Osazuwa E, Osemene GI, et al. Clinical study comparing probiotic Lactobacillus GR-1 and RC-14 with metronidazole vaginal gel to treat symptomatic bacterial vaginosis. Microbes Infect. 2006;8:2772-6. doi: 10.1016/j.micinf.2006.08.008.
  • Mastromarino P, Macchia S, Meggiorini L, et al. Effectiveness of Lactobacillus-containing vaginal tablets in the treatment of symptomatic bacterial vaginosis. Clin Microbiol Infect. 2009;15:67-74. doi: 10.1111/j.1469-0691.2008.02112.x.
  • Krauss-Silva L, Moreira ME, Alves MB, et al. A randomized controlled trial of probiotics for the prevention of spontaneous preterm delivery associated with bacterial vaginosis: preliminary results. Trials. 2011;12:239. doi: 10.1186/1745-6215-12-239.
  • Stojanović N, Plećaš D, Plešinac S. Normal vaginal flora, disorders and application of probiotics in pregnancy. Arch Gynecol Obstet. 2012;286(2):325-32. doi: 10.1007/s00404-012-2293-7.
  • Petricevic L, Witt A. The role of Lactobacillus casei rhamnosus Lcr 35 in restoring the normal vaginal flora after antibiotic treatment of bacterial vaginosis. BJOG. 2008;115:1369-74. doi: 10.1111/j.1471-0528.2008.01882.x.
  • Парфенюк Р.Л. Микробиологические основы пероральной фаготерапии гнойно-воспалительных заболеваний: дис. ... канд. биол. наук. – М., 2003. – 101 c. [Parfenyuk RL. Mikrobiologicheskie osnovy peroral’noi fagoterapii gnoino-vospalitel’nykh zabolevanii. [dissertation] Moscow; 2003. 101 p. (In Russ.)]
  • Новахова Ж.Д., Буданов П.В., Стрижаков А.Н., Чурганова А.А. Современные возможности селективной антибактериальной терапии в акушерстве и гинекологии // Трудный пациент. – 2014. – № 12. – C. 36–38. [Novakhova ZhD, Budanov PV, Strizhakov AN, Churganova AA. Modern Opportunities for Selective Antibiotic Treatment in Obstetrics and Gynecology. Difficult Patient. 2014;(12):36-8. (In Russ.)]
  • Slopek S, Weber-Dabrowska В, Dabrowski M, et al. Results of bacteriophage treatment of suppurative bacterial infections in the years, 1986. Arch Immunol Ther Exp. 1987;35:569-83.
  • Белопольская Х.А., Сидорова И.С., Шахгире ева Л.С., Белопольский А.А. Возможности фаговой терапии гинекологической инфекции // Трудный пациент. – 2014. – № 8–9. – С. 6–10. [Belopolskaya KhA, Sidorova IS, Shakhgireeva LS, Belopolskiy AA. Perspectives of Phages Therapy for Gynecological Infections. Difficult Patient. 2014;(8-9):6-10. (In Russ.)]

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