The role of probiotics in maintaining vaginal ecosystem

A disturbed vaginal ecosystem is characterized by reduced or non-existing lactobacillary flora and damaged vaginal epithelium. It may not always be apparent whether alterations of the vaginal epithelium or pathogenic microorganisms are the primary cause of a disturbed vaginal ecosystem. Estriol plays a key role in developing and maintaining a healthy vaginal epithelium, stimulating cell growth and differentiation, increases epithelial thickness, and also promotes glycogen synthesis, which is required to maintain an acidic environment. Estriol deficiency results in the vulvovaginal atrophy and the development of atrophic vaginitis. In turn, Lactobacillus acidophilus maintains a healthy microbiome, protecting against infections and creating an acidic environment unfavourable for the growth of pathogens. In recent years, an increasing interest has been developed in probiotics with the belief that probiotics could be able to restore the vaginal microbiota health. A review of scientific articles on the use of an ultra-low-dose vaginal estriol 0.03 mg in combination with Lactobacillus acidophilus to normalize the vaginal microbiota and treat vaginal infections has been conducted. An analysis of published clinical studies and meta-analyses on the use of probiotics in vaginal infections showed the mechanisms of action of probiotics, their biological role and clinical effects. The integration of probiotics into the treatment and prevention of bacterial vaginosis is growing more urgent. The results of numerous studies and meta-analyses confirmed their high efficacy and safety. The supplementation of standard antibiotic therapy with probiotics improves cure rates, restores normal vaginal microflora and reduces the risk of relapse. Therefore, further studies on the use of probiotics to develop more effective and personalized treatment strategies providing long-term results are needed. The publication of new evidence will make it possible to introduce best practices into clinical practice and ensure a healthier future for patients worldwide.

1. Hill C, Guarner F, Reid G, Gibson GR, Merenstein DJ, Pot B et al. Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol. 2014;11(8):506–514. https://doi.org/10.1038/nrgastro.2014.66.

2. Redondo-Lopez V, Cook RL, Sobel JD. Emerging role of lactobacilli in the control and maintenance of the vaginal bacterial microflora. Rev Infect Dis. 1990;12(5):856–872. https://doi.org/10.1093/clinids/12.5.856.

3. Sturdee DW, Panay N. Recommendations for the management of postmenopausal vaginal atrophy. Climacteric. 2010;13(6):509–522. https://doi.org/10.3109/13697137.2010.522875.

4. Head KA. Estriol: safety and efficacy. Altern Med Rev. 1998;3(2):101–113. Available at: https://pubmed.ncbi.nlm.nih.gov/9577246.

5. Witkin SS, Linhares IM, Giraldo P. Bacterial flora of the female genital tract: function and immune regulation. Best Pract Res Clin Obstet Gynaecol. 2007;21(3):347–354. https://doi.org/10.1016/j.bpobgyn.2006.12.004.

6. Lamont RF, Sobel JD, Akins RA, Hassan SS, Chaiworapongsa T, Kusanovic JP et al. The vaginal microbiome: new information about genital tract flora using molecular based techniques. BJOG. 2011;118(5):533–549. https://doi.org/10.1111/j.1471-0528.2010.02840.x.

7. Fredricks DN, Fiedler TL, Marrazzo JM. Molecular identification of bacteria associated with bacterial vaginosis. N Engl J Med. 2005;353(18):1899– 1911. https://doi.org/10.1056/NEJMoa043802.

8. Reid G, Bruce AW. Selection of lactobacillus strains for urogenital probiotic applications. J Infect Dis. 2001;183(Suppl. 1):S77–80. https://doi.org/10.1086/318841.

9. Reid G, Younes JA, van der Mei HC, Gloor GB, Knight R, Busscher HJ. Microbiota restoration: natural and supplemented recovery of human microbial communities. Nat Rev Microbiol. 2011;9(1):27–38. https://doi.org/10.1038/nrmicro2473.

10. Barbes C, Boris S. Potential role of lactobacilli as prophylactic agents against genital pathogens. AIDS Patient Care STDS. 1999;13(12):747–751. https://doi.org/10.1089/apc.1999.13.747.

11. Schöni M, Graf F, Meier B. Behandlung von Vaginalstörungen mit Döderlein-Keimen. SAZ. 1988;126:139–142.

12. Unlü C, Donders G. Use of lactobacilli and estriol combination in the treatment of disturbed vaginal ecosystem: a review. J Turk Ger Gynecol Assoc. 2011;12(4):239–246. https://doi.org/10.5152/jtgga.2011.57.

13. Gaspar C, Donders GG, Palmeira-de-Oliveira R, Queiroz JA, Tomaz C, Martinez-de-Oliveira J, Palmeira-de-Oliveira A. Bacteriocin production of the probiotic Lactobacillus acidophilus KS400. AMB Express. 2018;8(1):153. https://doi.org/10.1186/s13568-018-0679-z.

14. Buggio L, Somigliana E, Borghi A, Vercellini P. Probiotics and vaginal microecology: fact or fancy? BMC Women’s Health. 2019;19(1):25. https://doi.org/10.1186/s12905-019-0723-4.

15. Kirihara N, Kamitomo M, Tabira T, Hashimoto T, Taniguchi H, Maeda T. Effect of probiotics on perinatal outcome in patients at high risk of preterm birth. J Obstet Gynaecol Res. 2018;44(2):241–247. https://doi.org/10.1111/jog.13497.

16. Прилепская ВН, Кира ЕФ, Аполихина ИА, Байрамова ГР, Гомберг МА, Минкина ГН и др. Клинические рекомендации по диагностике и лечению заболеваний, сопровождающихся патологическими выделениями из половых путей женщин. М.; 2019. Режим доступа: https://library.mededtech.ru/rest/documents/Rek/.

17. Tan H, Fu Y, Yang C, Ma J. Effects of metronidazole combined probiotics over metronidazole alone for the treatment of bacterial vaginosis: a meta-analysis of randomized clinical trials. Arch Gynecol Obstet. 2017;295(6):1331–1339. https://doi.org/10.1007/s00404-017-4366-0.

18. Oduyebo OO, Anorlu RI, Ogunsola FT. The effects of antimicrobial therapy on bacterial vaginosis in non-pregnant women. Cochrane Database Syst Rev. 2009;(3):CD006055. https://doi.org/10.1002/14651858.CD006055.pub2.

19. Huang H, Song L, Zhao W. Effects of probiotics for the treatment of bacterial vaginosis in adult women: a meta-analysis of randomized clinical trials. Arch Gynecol Obstet. 2014;289(6):1225–1234. https://doi.org/10.1007/s00404-013-3117-0.

20. Chen R, Li R, Qing W, Zhang Y, Zhou Z, Hou Y et al. Probiotics are a good choice for the treatment of bacterial vaginosis: a meta-analysis of randomized controlled trial. Reprod Health. 2022;19(1):137. https://doi.org/10.1186/s12978-022-01449-z.

21. Sgibnev A, Kremleva E. Probiotics in addition to metronidazole for treatment Trichomonas vaginalis in the presence of BV: a randomized, placebo-controlled, double-blind study. Eur J Clin Microbiol Infect Dis. 2020;39(2):345–351. https://doi.org/10.1007/s10096-019-03731-8.

22. Vieira-Baptista P, Stockdale CK, Sobel J (eds.). International Society for the Study of Vulvovaginal Disease recommendations for the diagnosis and treatment of vaginitis. Lisbon: Admedic; 2023. Available at: https://www.issvd.org/application/files/4916/7897/2719/ISSVD_recommendations_for_the_diagnosis_and_treatment_of_vaginitis.pdf.

23. Donders GG, Van Bulck B, Van de Walle P, Kaiser RR, Pohlig G, Gonser S et al. Effect of lyophilized lactobacilli and 0.03 mg estriol (Gynoflor®) on vaginitis and vaginosis with disrupted vaginal microflora: a multicenter, randomized, single-blind, active-controlled pilot study. Gynecol Obstet Invest. 2010;70(4):264–272. https://doi.org/10.1159/000314016.

24. Thanaboonyawat I, Pothisan S, Petyim S, Laokirkkiat P. Pregnancy outcomes after vaginal probiotic supplementation before frozen embryo transfer: a randomized controlled study. Sci Rep. 2023;13(1):11892. https://doi.org/10.1038/s41598-023-39078-6.