Lactic acid as a key factor in restoring vaginal microbiota: physiological and clinical aspects

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Abstract

Background: Despite the efficacy of antimicrobial therapy for inflammatory diseases of the lower genital tract, the high recurrence rate and growing resistance of microorganisms make it necessary to search for and implement alternative or adjuvant approaches aimed at restoring a healthy vaginal microbiome. Lactic acid is a key metabolite of lactobacilli and it plays a vital role in maintaining the vaginal microbiota by providing an acidic environment that inhibits the growth of pathogens and modulates the local immune response.

Objective: To organize the current literature data on the role of lactic acid in the pathogenesis of bacterial and viral vaginitis and on the use of acid-containing medications to restore vaginal microbiota, maintain fertility; to analyze the data in menopausal and pregnant women.

Materials and methods: The Russian and foreign databases, namely eLibrary, PubMed, and Russian Science Citation Index (RSCI), were analyzed for the keywords, ‘lactic acid’, ‘lactobacilli’, ‘microbiota’, ‘dysbiosis’, ‘bacterial vaginosis’, ‘human papillomavirus’, ‘genital herpes’, and ‘genital infections’. Literature sources were selected for analysis according to the objective.

Results: This article summarizes the data on the physiological functions of lactic acid and its mechanisms of action, including its antimicrobial, viricidal and immunomodulatory effects. The possibilities of using lactic acid in the therapy of bacterial vaginosis, vaginitis of nonspecific and mixed etiology, viral infections in pregnant and postmenopausal women are considered. The article highlights the data on the role of lactic acid in maintaining fertility, preparing the endometrium for implantation and reducing the risk of obstetric complications. The high safety of topical application of lactic acid is emphasized, especially in the context of the limitations of antibacterial therapy in pregnant women and in the setting of recurrent bacterial vaginosis.

Conclusion: Lactic acid is not only a metabolite providing physiological acidity of the vaginal environment, but also an active component of innate immunity, capable of resisting both bacterial and viral infections. Its use in vaginal preparations represents a valid strategy for restoring vaginal microbiota and preventing recurrent vaginal infections.

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About the authors

Niso M. Nazarova

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

Author for correspondence.
Email: n_nazarova@oparina4.ru
ORCID iD: 0000-0001-9499-7654

Dr. Med. Sci., Leading Researcher

Russian Federation, Moscow

Anastasia R. Devyatkina

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

Email: grinasta26@mail.ru
ORCID iD: 0009-0006-1742-7555

Resident

Russian Federation, Moscow

Elena A. Mezhevitinova

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

Email: mejevitinova@mail.ru
ORCID iD: 0000-0003-2977-9065

Dr. Med. Sci., Leading Researcher at the Scientific Polyclinic Department

Russian Federation, Moscow

Vera N. Prilepskaya

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

Email: v_prilepskaya@oparina4.ru
ORCID iD: 0000-0003-3993-7629

Dr. Med. Sci., Professor, Honored Scientist of the Russian Federation, Head of the Scientific Polyclinic Department

Russian Federation, Moscow

Leyla E. Alieva

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

Email: leylaalieva00@mail.ru
ORCID iD: 0009-0008-3417-6721

Resident

Russian Federation, Moscow

Elena G. Sycheva

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

Email: el.bona@mail.ru
ORCID iD: 0000-0002-2527-7853

PhD, Doctor at the Scientific Polyclinic Department

Russian Federation, Moscow

Vera V. Muravieva

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

Email: v_muravieva@oparina4.ru
ORCID iD: 0000-0003-0383-0731

PhD (Bio), Senior Researcher at the Laboratory of Molecular Microbiology, Department of Microbiology and Clinical Pharmacology

Russian Federation, Moscow

References

  1. Plummer E.L., Bradshaw C.S., Doyle M., Fairley C.K., Murray G.L., Bateson D. et al. Lactic acid-containing products for bacterial vaginosis and their impact on the vaginal microbiota: A systematic review. PLoS One. 2021; 16(2): e0246953. https://dx.doi.org/10.1371/journal.pone.0246953
  2. Ravel J., Gajer P., Abdo Z., Schneider G.M., Koenig S.S., McCulle S.L. et al. Vaginal microbiome of reproductive-age women. Proc. Natl. Acad. Sci. U. S. A. 2011; 108 Suppl. 1(Suppl. 1):4680-7. https://dx.doi.org/10.1073/pnas.1002611107
  3. Tachedjian G., Aldunate M., Bradshaw C.S., Cone R.A. The role of lactic acid production by probiotic Lactobacillus species in vaginal health. Res. Microbiol. 2017; 168(9-10): 782-92. https://dx.doi.org/10.1016/j.resmic.2017.04.001
  4. Aldunate M., Tyssen D., Johnson A., Zakir T., Sonza S., Moench T. et al. Vaginal concentrations of lactic acid potently inactivate HIV. J. Antimicrob. Chemother. 2013; 68(9): 2015-25. https://dx.doi.org/10.1093/jac/dkt156
  5. Hearps A.C., Tyssen D., Srbinovski D., Bayigga L., Diaz D.J.D., Aldunate M. et al. Vaginal lactic acid elicits an anti-inflammatory response from human cervicovaginal epithelial cells and inhibits production of pro-inflammatory mediators associated with HIV acquisition. Mucosal. Immunol. 2017; 10(6): 1480-90. https://dx.doi.org/10.1038/mi.2017.27
  6. Martin D.H. The microbiota of the vagina and its influence on women's health and disease. Am. J. Med. Sci. 2012; 343(1): 2-9. https://dx.doi.org/10.1097/MAJ.0b013e31823ea228
  7. Ilhan Z.E., Łaniewski P., Thomas N., Roe D.J., Chase D.M., Herbst-Kralovetz M.M. Deciphering the complex interplay between microbiota, HPV, inflammation and cancer through cervicovaginal metabolic profiling. EBioMedicine. 2019; 44: 675-90. https://dx.doi.org/10.1016/j.ebiom.2019.04.028
  8. Mastromarino P., Hemalatha R., Barbonetti A., Cinque B., Cifone M.G., Tammaro F. et al. Biological control of vaginosis to improve reproductive health. Indian J. Med. Res. 2014; 140 Suppl.(Suppl. 1):S91-7.
  9. Muzny C.A., Balkus J., Mitchell C., Sobel J.D., Workowski K., Marrazzo J. et al. Diagnosis and management of bacterial vaginosis: summary of evidence reviewed for the 2021 Centers for Disease Control and Prevention Sexually Transmitted Infections Treatment Guidelines. Clin. Infect. Dis. 2022; 74(Suppl._2): S144-S151. https://dx.doi.org/10.1093/cid/ciac021
  10. Bradshaw C.S., Morton A.N., Hocking J., Garland S.M., Morris M.B., Moss L.M. et al. High recurrence rates of bacterial vaginosis over the course of 12 months after oral metronidazole therapy and factors associated with recurrence. J. Infect. Dis. 2006; 193(11): 1478-86. https://dx.doi.org/10.1086/503780
  11. Mendling W., Shazly M.A.E., Zhang L. The role of lactic acid in the management of bacterial vaginosis: a systematic literature review. Future Pharmacol. 2022; 2(3): 198-213. https://dx.doi.org/10.3390/futurepharmacol2030014
  12. Armstrong-Buisseret L., Brittain C., Kai J., David M., Anstey Watkins J., Ozolins M. et al. Lactic acid gel versus metronidazole for recurrent bacterial vaginosis in women aged 16 years and over: the VITA RCT. Health Technol. Assess. 2022; 26(2): 1-170. https://dx.doi.org/10.3310/ZZKH4176
  13. Mayer B.T., Srinivasan S., Fiedler T.L., Marrazzo J.M., Fredricks D.N., Schiffer J.T. Rapid and profound shifts in the vaginal microbiota following antibiotic treatment for bacterial vaginosis. J. Infect. Dis. 2015; 212(5): 793-802. https://dx.doi.org/10.1093/infdis/jiv079
  14. Tidbury F., Brülhart G., Müller G., Pavicic E., Weidlinger S., Eichner G. et al. Effectiveness and tolerability of lactic acid vaginal gel compared to oral metronidazole in the treatment of acute symptomatic bacterial vaginosis: a multicenter, randomized-controlled, head-to-head pilot study. BMC Womens Health. 2025; 25(1): 7. https://dx.doi.org/10.1186/s12905-024-03513-1
  15. Liu P., Lu Y., Li R., Chen X. Use of probiotic lactobacilli in the treatment of vaginal infections: In vitro and in vivo investigations. Front. Cell. Infect. Microbiol. 2023; 13: 1153894. https://dx.doi.org/10.3389/fcimb.2023.1153894
  16. Delgado-Diaz D.J., Jesaveluk B., Hayward J.A., Tyssen D., Alisoltani A., Potgieter M. et al. Lactic acid from vaginal microbiota enhances cervicovaginal epithelial barrier integrity by promoting tight junction protein expression. Microbiome. 2022; 10(1): 141. https://dx.doi.org/10.1186/s40168-022-01337-5
  17. James S.H., Prichard M.N. Current and future therapies for herpes simplex virus infections: mechanism of action and drug resistance. Curr. Opin. Virol. 2014; 8: 54-61. https://dx.doi.org/10.1016/j.coviro.2014.06.003
  18. Conti C., Malacrino C., Mastromarino P. Inhibition of herpes simplex virus type 2 by vaginal lactobacilli. J. Physiol. Pharmacol. 2009; 60 Suppl. 6: 19-26.
  19. Elebeedy D., Ghanem A., Aly S.H., Ali M.A., Faraag A.H.I., El-Ashrey M.K. et al. Synergistic antiviral activity of Lactobacillus acidophilus and Glycyrrhiza glabra against Herpes Simplex-1 Virus (HSV-1) and Vesicular Stomatitis Virus (VSV): experimental and in silico insights. BMC Microbiol. 2023; 23(1):173. https://dx.doi.org/10.1186/s12866-023-02911-z
  20. Zhou Z.W., Long H.Z., Cheng Y., Luo H.Y., Wen D.D., Gao L.C. From microbiome to inflammation: the key drivers of cervical cancer. Front. Microbiol. 2021; 12: 767931. doi: 10.3389/fmicb.2021.767931
  21. van de Wijgert J.H.H.M., Jespers V. The global health impact of vaginal dysbiosis. Res. Microbiol. 2017; 168(9-10): 859-64. https://dx.doi.org/ 10.1016j.resmic.2017.02.003
  22. Mitra A., MacIntyre D.A., Marchesi J.R., Lee Y.S., Bennett P.R., Kyrgiou M. The vaginal microbiota, human papillomavirus infection and cervical intraepithelial neoplasia: what do we know and where are we going next? Microbiome. 2016; 4(1): 58. https://dx.doi.org/10.1186/ s40168-016-0203-0
  23. Mitra A., MacIntyre D.A., Ntritsos G., Smith A., Tsilidis K.K., Marchesi J.R. et al. The vaginal microbiota associates with the regression of untreated cervical intraepithelial neoplasia 2 lesions. Nat. Commun. 2020; 11(1): 1999. https://dx.doi.org/10.1038/s41467-020-15856-y
  24. So K.A., Yang E.J., Kim N.R., Hong S.R., Lee J.H., Hwang C.S. et al. Changes of vaginal microbiota during cervical carcinogenesis in women with human papillomavirus infection. PLoS One. 2020; 15(9): e0238705. https:// dx.doi.org/10.1371/journal.pone.0238705
  25. 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
  26. Mitra A., MacIntyre D.A., Lee Y.S., Smith A., Marchesi J.R., Lehne B. et al. Cervical intraepithelial neoplasia disease progression is associated with increased vaginal microbiome diversity. Sci. Rep. 2015; 5: 16865. https://dx.doi.org/10.1038/srep16865
  27. Di Paola M., Sani C., Clemente A.M., Iossa A., Perissi E., Castronovo G. et al. Characterization of cervico-vaginal microbiota in women developing persistent high-risk Human Papillomavirus infection. Sci. Rep. 2017; 7(1): 10200. https://dx.doi.org/10.1038/s41598-017-09842-6
  28. Palma E., Recine N., Domenici L., Giorgini M., Pierangeli A., Panici P.B. Long-term Lactobacillus rhamnosus BMX 54 application to restore a balanced vaginal ecosystem: a promising solution against HPV-infection. BMC Infect. Dis. 2018; 18(1): 13. https://dx.doi.org/10.1186/s12879-017-2938-z
  29. Cohen C.R., Lingappa J.R., Baeten J.M., Ngayo M.O., Spiegel C.A., Hong T. et al. Bacterial vaginosis associated with increased risk of female-to-male HIV-1 transmission: a prospective cohort analysis among African couples. PLoS Med. 2012; 9(6): e1001251. https://dx.doi.org/10.1371/journal.pmed.1001251
  30. Ñahui Palomino R.A., Zicari S., Vanpouille C., Vitali B., Margolis L. Vaginal Lactobacillus inhibits HIV-1 replication in human tissues ex vivo. Front. Microbiol. 2017; 8: 906. https://dx.doi.org/10.3389/fmicb.2017.00906
  31. Chen H., Min S., Wang L., Zhao L., Luo F., Lei W. et al. Lactobacillus modulates Chlamydia infectivity and genital tract pathology in vitro and in vivo. Front. Microbiol. 2022; 13: 877223. https://dx.doi.org/10.3389/ fmicb.2022.877223
  32. Graver M.A., Wade J.J. The role of acidification in the inhibition of Neisseria gonorrhoeae by vaginal lactobacilli during anaerobic growth. Ann. Clin. Microbiol. Antimicrob. 2011; 10: 8. https://dx.doi.org/ 10.1186/1476-0711-10-8
  33. Brotman R.M., Bradford L.L., Conrad M., Gajer P., Ault K., Peralta L. et al. Association between Trichomonas vaginalis and vaginal bacterial community composition among reproductive-age women. Sex. Transm. Dis. 2012; 39(10): 807-12. https://dx.doi.org/10.1097/OLQ.0b013e3182631c79
  34. Moore K.R., Tomar M., Taylor B.D., Gygax S.E., Hilbert D.W., Baird D.D. Mycoplasma genitalium and bacterial vaginosis-associated bacteria in a non-clinic-based Sample of African American women. Sex. Transm. Dis. 2021; 48(2): 118-22. https://dx.doi.org/10.1097/OLQ.0000000000001275
  35. Stapleton A.E. The vaginal microbiota and urinary tract infection. Microbiol. Spectr. 2016; 4(6): 10.1128/microbiolspec.UTI-0025-2016. https://dx.doi.org/10.1128/microbiolspec.UTI-0025-2016
  36. Diebold R., Schopf B., Stammer H., Mendling W. Vaginal treatment with lactic acid gel delays relapses in recurrent urinary tract infections: results from an open, multicentre observational study. Arch. Gynecol. Obstet. 2021; 304(2): 409-17. https://dx.doi.org/10.1007/s00404-021-06040-8
  37. Alperin M., Burnett L., Lukacz E., Brubaker L. The mysteries of menopause and urogynecologic health: clinical and scientific gaps. Menopause. 2019; 26(1): 103-11. https://dx.doi.org/10.1097/GME.0000000000001209
  38. Gänzle M.G., Follador R. Metabolism of oligosaccharides and starch in lactobacilli: a review. Front. Microbiol. 2012; 3: 340. https://dx.doi.org/10.3389/fmicb.2012.00340
  39. Mitchell C., Marrazzo J. Bacterial vaginosis and the cervicovaginal immune response. Am. J. Reprod. Immunol. 2014; 71(6): 555-63. https://dx.doi.org/10.1111/aji.12264
  40. Chen Q., Wang H., Wang G., Zhao J., Chen H., Lu X. et al. Lactic acid bacteria: a promising tool for menopausal health management in women. Nutrients. 2022; 14(21): 4466. https://dx.doi.org/10.3390/nu14214466
  41. Koedooder R., Singer M., Schoenmakers S., Savelkoul P.H.M., Morré S.A., de Jonge J.D. et al. The vaginal microbiome as a predictor for outcome of in vitro fertilization with or without intracytoplasmic sperm injection: a prospective study. Hum. Reprod. 2019; 34(6): 1042-54. https://dx.doi.org/10.1093/ humrep/dez065
  42. Moreno I., Codoñer F.M., Vilella F., Valbuena D., Martinez-Blanch J.F., Jimenez-Almazán J. et al. Evidence that the endometrial microbiota has an effect on implantation success or failure. Am. J. Obstet. Gynecol. 2016; 215(6): 684-703. https://dx.doi.org/10.1016/j.ajog.2016.09.075
  43. Lan J., Chen C. The role of lactic acid bacteria in maintaining vaginal internal environment homeostasis in patients with infertility. Microb. Pathog. 2023; 176: 106004. https://dx.doi.org/10.1016/j.micpath.2023.106004
  44. Cocomazzi G., Contu V., De Stefani S., Del Pup L., Buccheri M., Antinori M. et al. Refining unfavorable vaginal microbial community in infertile women subjected to precision probiotic intervention: An exploratory single-arm, prospective, open-label, interventional study. Microorganisms. 2025; 13(3): 547. https://dx.doi.org/10.3390/microorganisms13030547
  45. Fettweis J.M., Serrano M.G., Brooks J.P., Edwards D.J., Girerd P.H., Parikh H.I. et al. The vaginal microbiome and preterm birth. Nat. Med. 2019; 25(6): 1012-21. https://dx.doi.org/10.1038/s41591-019-0450-2
  46. Bonneton M., Huynh B.T., Seck A., Bercion R., Sarr F.D., Delarocque-Astagneau E. et al. Bacterial vaginosis and other infections in pregnant women in Senegal. BMC Infect. Dis. 2021; 21(1): 1090. https://dx.doi.org/10.1186/s12879-021-06767-4
  47. Hoyme U.B., Hesse M. Reduced incidence of early preterm birth in the State of Thuringia following an intravaginal pH-self-monitoring screening program. Arch. Gynecol. Obstet. 2020; 302(1):1-4. https://dx.doi.org/10.1007/ s00404-020-05574-7
  48. Holst E., Brandberg A. Treatment of bacterial vaginosis in pregnancy with a lactate gel. Scand. J. Infect. Dis. 1990; 22(5): 625-6. https:// dx.doi.org/10.3109/00365549009027109
  49. Borges S., Silva J., Teixeira P. The role of lactobacilli and probiotics in maintaining vaginal health. Arch. Gynecol. Obstet. 2014; 289(3): 479-89. https://dx.doi.org/10.1007/s00404-013-3064-9
  50. Petricevic L., Domig K.J., Nierscher F.J., Sandhofer M.J., Fidesser M., Krondorfer I. et al. Characterisation of the vaginal Lactobacillus microbiota associated with preterm delivery. Sci. Rep. 2014; 4: 5136. https://dx.doi.org/10.1038/srep05136
  51. Летяева О.И. Бактериальный вагиноз: современные возможности и перспективы длительного контроля. Российский вестник акушера-гинеколога. 2019; 19(2): 100-4. [Letyaeva O.I. Bacterial vaginosis: current opportunities and prospects for long-term control. Russian Bulletin of Obstetrician-Gynecologist. 2019; 19(2): 100-4. (in Russian)]. https://dx.doi.org/10.17116/rosakush201919021100
  52. Кира Е.Ф., Пекарев О.Г., Молчанов О.Л., Мальцева Л.И., Аксененко В.А., Селихова М.С., Летяева О.И., Минаев Н.Н., Коршакова Н.Ю. Сравнительный анализ эффективности и безопасности параллельного или последовательного сочетания метронидазола с молочной кислотой и двухэтапного метода метронидазол плюс пробиотик. Многоцентровое рандомизированное контролируемое исследование. Акушерство и гинекология. 2016; 9: 87-93. [Kira E.F., Pekarev O.G., Molchanov O.L., Maltseva L.I., Aksenenko V.A., Selikhova M.S., Letyaeva O.I., Minaev N.N., Korshakova N.Yu. Comparative analysis of the efficiency and safety of parallel or sequential combination of metronidazole with lactic acid and a two-stage regimen including metronidazole plus a probiotic: A multicenter randomized controlled study. Obstetrics and Gynecology. 2016; (9): 87-93. (in Russian)]. https://dx.doi.org/10.18565/aig.2016.9.87-93
  53. Радзинский В.Е., Хамошина М.Б., Оразов М.Р., Тулупова М.С., Пестрикова Т.Ю., Ярмолинская М.И., Рымашевский А.Н. Результаты многоцентрового наблюдательного исследования: терапия острого вагинита неспецифической и смешанной этиологии у пациенток репродуктивного возраста. Акушерство и гинекология. 2019; 8: 150-8. [Radzinskiy V.E., Khamoshina M.B., Orazov M.R., Tulupova M.S., Pestrikova T.Yu., Yarmolinskaya M.I., Rymashevsky A.N. Results of a multicenter observational study: therapy for acute non-specific and mixed vaginitis in reproductive-aged patients. Obstetrics and Gynecology. 2019; (8): 150-8 (in Russian)]. https://dx.doi.org/10.18565/aig.2019.8.150-158
  54. Кира Е.Ф., Рыбальченко О.В., Орлова О.Г., Коршакова Н.Ю. Изучение активности молочной кислоты in vitro и ее значение для клинической практики в лечении инфекций влагалища. Акушерство и гинекология. 2017; 11: 84-91. [Kira E.F., Rybalchenko O.V., Orlova O.G., Korshakova N.Yu. Investigation of the in vitro activity of lactic acid and its value for clinical practice in the treatment of vaginal infections. Obstetrics and Gynecology. 2017; (11): 84-91. (in Russian)]. https://dx.doi.org/10.18565/aig.2017.11.84-91

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