Pharmacological and clinical aspects of oral preparations of lactobacilli usage in treatment of vaginal dysbiosis

• Evgenia V. Shikh

Abstract

Imbalance of the normal GIT (gastrointestinal tract) microbiota composition predisposes to immunodeficiency conditions, which are the background for development of chronic inflammatory genital diseases and their relapses. Medical use of oral probiotics in gynecology makes it possible to implement an integrated approach to normalization of biocenosis in several biotopes at once. Immunological component of probiotics action, as well as systemic effects, can be provided only in case of oral administration. L. rhamnosus GR-1 and L. reuteri RC-14 (Vagilak preparation) strains are known to remain viable after passing through gastrointestinal tract. They are also representatives of normal vaginal flora and have good adhesion ability. Oral administration leads to vaginal colonization by these strains. There is a synergy of action: L. rhamnosus GR-1 has a pronounced antagonism to gram-negative coccal flora and resistance to spermicides (nonoxilone-9); L. reuteri RC-14 has a pronounced antagonism to gram-positive coccal flora and produces hydrogen peroxide. Combination of L. reuteri RC-14 and L. Rhamnosus GR-1 inhibits growth of C. albicans and also exhibits pronounced antagonistic activity against all C. glabrata strains. Orally administered L. rhamnosus GR-1 and L. reuteri RC have an evidence base for efficacy in vaginal bacterial dysbiosis when administered concurrently with eradication therapy, when used as a second stage; when used to prevent relapse.

Keywords:oral probiotics, vaginal dysbiosis, lactobacilli, L. rhamnosus GR-1, L reuteri RC-14

References

1. Lynch S.V., Pedersen O. The human intestinal microbiome in health and disease. N Engl J Med. 2016; 375: 2369.

2. Popkova S.M., et al. Microecological combinations of vaginal and intestinal biotopes in women with inflammatory diseases of the lower floor of the genital tract and adolescent girls with ovarian dysfunction. Byulleten' SO RAMN [Bulletin SB RAMS] [Bulletin of the Siberian Branch of the Russian Academy of Medical Sciences]. 2013; 33 (4): 77-84. (in Russian)

3. Thaiss C.A., Zmora N., Levy M., Elinav E. The microbiome and innate immunity. Nature. 2016; 535: 65.

4. Biagi E., Candela M., Fairwether-Taight S., Franceschi C., Brigidi P. Ageing of human metaorganism: the microbial counterpart. Age. 2012; 34: 247-26.

5. Heczko P.B., et al. Supplementation of standard antibiotic therapy with oral probiotics for bacterial vaginosis and aerobic vaginitis: a randomised, double-blind, placebo-controlled trial. BMC Womens Health. 2015; 15: 115.

6. Potapov V.A. Probiotics in gynecology. Another fashion or perceived need (analytical review). З турботою про жiнку [With Care for the Woman]. 2015; (1): 10-5. (in Russian)

7. ILSI EU Concise Monograpth Series. Probiotics, Prebiotics and the Gut Microbiota. 2013.

8. Drozdov V.N., Vorob'eva O.A., Astapovsky A.A., Shikh E.V. Probiotics in pediatrics: how to choose effective and safety specimen for a child. Voprosy sovremennoy pediatrii [Problems of Modern Pediatrics]. 2019; 18 (4): 277-84. DOI: https://doi.org/10.15690/vsp.v18i4.2045 (in Russian)

9. Wolf A., Moissl-Eichinger C., Perras A., et al. The salivary microbiome as an indicator of carcinogenesis in patients with oropharyngeal squamous cell carcinoma: a pilot study. Sci Rep. 2017; 7 (1): 5867. DOI: https://doi.org/10.1038/s41598-017-06361-2

10. Kira E.F. Bacterial vaginosis. Моscow: MIA, 2012: 472 р. (in Russian)

11. Irkitova A.N., Kagan Ya.R., Sergeeva I.Ya. Properties, ecological aspects and practical significance of acidophilus bacillus. 1. Description and habitat. In: Siberian Research Institute of Cheese Making of the Siberian Russian Academy of Agricultural Sciences. Barnaul. Issue 8. Actual Problems of Technology and Milk Processing Technology: Collection of Scientific Papers. Barnaul, 2011: 207-12. (in Russian)

12. Nazarenko L.G., Solov'eva N.P. The use of oral probiotics as an alternative clinical strategy for the prevention of obstetric and perinatal infections. Zdorov'e zhenshchiny [Woman's Health]. 2013; 6 (82): 91-6. (in Russian)

13. Harkins C.P., Kong H.H., Segre J.A. Manipulating the human microbiome to manage disease. JAMA. 2020; 323: 303.

14. Lazzaro B.P., Zasloff M., Rolff J. Antimicrobial peptides: application informed by evolution. Science. 2020; 368 (6490): eaau5480.

15. Zasloff M. Antimicrobial peptides of multicellular organisms: my perspective. Adv Exp Med Biol. 2019; 1117: 3.

16. Cleusix V., Lacroix C., Vollenweider S., et al. Inhibitory activity spectrum of reuterin produced by Lactobacillus reuteri against intestinal bacteria. BMC Microbiol. 2007; 7: 101. DOI: https://doi.org/10.1186/1471-2180-7-101

17. Grigg J.B., Sonnenberg G.F. Host-microbiota interactions shape local and systemic inflammatory diseases. J Immunol. 2017; 198: 564.

18. Zaslavskaya M.I., Makhrova T.V., Aleksandrova N.A., Ignatova N.I., Belova I.V., Tochilina A.G., et al. Prospects for using bacteriocins of normal microbiota in antibacterial therapy (review). Sovremennye tekhnologii v meditsine [Modern Technologies in Medicine]. 2019; 11 (3): 136-45. DOI: https://doi.org/10.17691/stm2019.11.3.17 (in Russian)

19. Berg R.D. Translocation of indigenous bacteria from the intestinal tract. In: Human Intestinal Microflora in Health and Disease. New York: Academic Press, 1983: 333-52.

20. Chicherin I.Yu., Pogorel'sky I.P., Lundovskikh I.A., Darmov I.V., Gavrilov K.E., Gorshkov A.S., et al. The role of probiotic microorganisms in translocation of intestinal microbiota in the peritoneal cavity and the bloodstream of experimental animals. Zhurnal mezhdunarodnoy meditsiny. Infektsionnye zabolevaniya [Journal of International Medicine. Infectious Diseases]. 2016; 2 (19): 87-99. (in Russian)

21. Nikitenko V.I., Kopylov V.A., Nikitenko M.V. Translocation of bacteria from the gastrointestinal tract is a natural defense mechanism. URL: http://bacoren.ucoz.ru/publ/1-1-0-1 (in Russian)

22. Zmora N., Soffer E., Elinav E. Transforming medicine with the microbiome. Sci Transl Med. 2019; 11 (477): eaaw1815.

23. Podoprigora G.I., Kafarskaya L.I., Baynov N.A., Shkoporov A.N. Acterial translocation from intestine: microbiological, immunological and pathophysiological aspects. Vestnik Rossiyskoy akademii meditsinskikh nauk [Bulletin of the Russian Academy of Medical Sciences]. 2015; 70 (6): 640-50. (in Russian)

24. Hase K., Kawano K., Nochi T., Pontes G.S., Fukuda S., Ebisawa M., et al. Uptake through glycoprotein 2 of FimH(+) bacteria by M cells initiates mucosal immune response. Nature. 2009; 462 (7270): 226-30. DOI: https://doi.org/10.1038/nature08529

25. Ohno H., Hase K. Glycoprotein 2 (GP2): grabbing the FimH bacteria into M cells for mucosal immunity. Gut Microbes. 2010; 1 (6): 407-10. DOI: https://doi.org/10.4161/gmic.1.6.14078.

26. Tikhomirov A.L., Sarsania S.I. Compliance in the treatment of vaginal dysbiosis. Meditsinskiy sovet [Medical Council]. 2019; (12): 146-52. DOI: https://doi.org/10.21518/2079-701X-2019-12-146-152 (in Russian)

27. Donders G.G. Treatment of bacterial vaginosis: what we have and what we miss. Expert Opin Pharmacother. 2014; 15 (5): 645-57. PMID: 24579850.

28. McMillan А., Dell M., Zellar M.P., Cribby S., et al. Disruption of urogenital biofilms by lactobacilli. Colloids Surf B Biointerfaces. 2011; 86: 58-64. DOI: https://doi.org/10.1016/j.colsurfb.2011.03.016

29. Martinez R.C., Seney S.L., Summers K.L., et al. Effect of Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 on the ability of Candida albicans to infect cells and induce inflammation. Microbiol Immunol. 2009; 53 (9): 487-95. DOI: https://doi.org/10.111Vj.1348-0421.2009.00154.x

30. Cianci A., Giordano R., Delia A., et al. Efficacy of Lactobacillus Rhamnosus GR-1 and of Lactobacillus Reuteri RC-14 in the treatment and prevention of vaginoses and bacterial vaginitis relapses. Minerva Ginecol. 2008; 60 (5): 369-76.

31. Kohler G.A., Assefa S., Reid G. Probiotic interference of Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 with the opportunistic fungal pathogen Candida albicans. Infect Dis Obstet Gynecol. 2012; 2012: 636474. DOI: https://doi.org/10.1155/2012/63647(46)4

32. Chew S.Y., Cheah Y.K., Seow H.F., et al. Probiotic Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 exhibit strong antifungal effects against vulvovaginal candidiasis-causing Candida glabrata isolates. J Appl Microbiol. 2015; 118 (5): 1180-90. DOI: https://doi.org/10.1111/jam.12772

33. Ho M., Chang Y.Y., Chang W.C., et al. Oral Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 to reduce Group B Streptococcus colonization in pregnant women: a randomized controlled trial. Taiwan J Obstet Gynecol. 2016; 55 (4): 515-18. DOI: https://doi.org/10.1016/j.tjog.2016.06.003

34. Evseev A.A., Pivovarova O.Yu. Combined therapy of bacterial vaginosis. Zdorov'e zhenshchiny [Woman's Health]. 2012; 4 (70): 142-46. (in Russian)

35. Radzinsky V.E., Ordiyants I.M., Apresyan S.V. The effectiveness of the correction of vaginal dysbiosis in the first trimester of pregnancy. Rossiyskiy vestnik akushera-ginekologa [Russian Bulletin of Obstetrician-Gynecologist]. 2010; 10 (3): 38-41. (in Russian)

36. Novikova S.V., Logutova L.S., Ignatieva M.A. Clinical evaluation of the efficacy and safety of the use of the drug vagilac for the treatment of bacterial vaginosis in pregnant women. Meditsinskiy sovet [Medical Council]. 2018; (13): 90-4. (in Russian)

37. Kudinov S.V., Sukhovey U., Petrov S.A. Efficiency of vaginal dysbiosis correction with probiotic vagilac before radiosurgical treatment in patients with cervical ectopia. Zhurnal akusherstva i zhenskikh bolezney [Journal of Obstetrics and Women's Diseases]. 2011; (6): 35-9. (in Russian)

38. Mezzasalma V., Manfrini E., Ferri E., Boccarusso M., Di Gennaro P., Schiano I., Michelotti A., Labra M. Orally administered multispecies probiotic formulations to prevent uro-genital infections: a randomized placebo-controlled pilot study. Arch Gynecol Obstet. 2017; 295 (1): 163-72.

39. 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.

40. Gavriilaki E., Brodsky R.A. Complementopathies and precision medicine. J Clin Invest. 2020; 130: 2152.

Литература

1. Lynch S.V., Pedersen O. The human intestinal microbiome in health and disease // N. Engl. J. Med. 2016. Vol. 375. P. 2369.

2. Попкова С.М. и др. Микроэкологические сочетания вагинального и кишечного биотопов у женщин с воспалительными заболеваниями нижнего этажа полового тракта и девочек-подростков с дисфункцией яичников // Бюллетень СО РАМН. 2013. Т. 33, № 4. С. 77-84.

3. Thaiss C.A., Zmora N., Levy M., Elinav E. The microbiome and innate immunity // Nature. 2016. Vol. 535. P. 65.

4. Biagi E., Candela M., Fairwether-Taight S., Franceschi C., Brigidi P. Ageing of human metaorganism: the microbial counterpart // Age. 2012. Vol. 34. P. 247-226.

5. Heczko P.B. et al. Supplementation of standard antibiotic therapy with oral probiotics for bacterial vaginosis and aerobic vaginitis: a randomised, double-blind, placebo-controlled trial // BMC Womens Health. 2015. Vol. 15. P. 115.

6. Потапов В.А. Пробиотики в гинекологии. Очередная мода или осознанная необходимость (аналитический обзор // З турботою про жiнку. 2015. № 1. С. 10-15.

7. ILSI EU Concise Monograpth Series. Probiotics, Prebiotics and the Gut Microbiota. 2013.

8. Дроздов В.Н., Воробьева О.А., Астаповский А.А., Ших Е.В. Пробиотики в педиатрии: как подойти к выбору эффективного и безопасного препарата для детей // Вопросы современной педиатрии. 2019. Т. 18, № 4. С. 277-284. DOI: https://doi.org/10.15690/vsp.v18i4.2045

9. Wolf A., Moissl-Eichinger C., Perras A. et al. The salivary microbiome as an indicator of carcinogenesis in patients with oropharyngeal squamous cell carcinoma: a pilot study // Sci. Rep. 2017. Vol. 7, N 1. P. 5867. DOI: https://doi.org/10.1038/s41598-017-06361-2

10. Кира Е.Ф. Бактериальный вагиноз. Москва : МИА, 2012. 472 с.

11. Иркитова А.Н., Каган Я.Р., Сергеева И.Я. Свойства, экологические аспекты и практическое значение ацидофильной палочки.

1. Описание и местообитание // Актуальные проблемы техники и технологии переработки молока : сборник научных трудов / Сибирский научно-исследовательский институт сыроделия Сибирского Российской академии сельскохозяйственных наук. Барнаул. Вып. 8. Барнаул, 2011. С. 207-212.

12. Назаренко Л.Г., Соловьева Н.П. Применение орального пробиотика как альтернативная клиническая стратегия профилактики акушерских и перинатальных инфекций // Здоровье женщины. 2013 № 6 (82). С. 91-96.

13. Harkins C.P., Kong H.H., Segre J.A. Manipulating the human microbiome to manage disease // JAMA. 2020. Vol. 323. P. 303.

14. Lazzaro B.P., Zasloff M., Rolff J. Antimicrobial peptides: application informed by evolution // Science. 2020. Vol. 368, N 6490. Article ID eaau5480.

15. Zasloff M. Antimicrobial peptides of multicellular organisms: my perspective // Adv. Exp. Med. Biol. 2019. Vol. 1117. P. 3.

16. Cleusix V., Lacroix C., Vollenweider S. et al. Inhibitory activity spectrum of reuterin produced by Lactobacillus reuteri against intestinal bacteria // BMC Microbiol. 2007. Vol. 7. P. 101. DOI: https://doi.org/10.1186/1471-2180-7-101

17. Grigg J.B., Sonnenberg G.F. Host-microbiota interactions shape local and systemic inflammatory diseases // J. Immunol. 2017. Vol. 198. P. 564.

18. Заславская М.И., Махрова Т.В., Александрова Н.А., Игнатова Н.И., Белова И.В., Точилина А.Г. и др. Перспективы использования бактериоцинов нормальной микробиоты в антибактериальной терапии (обзор) // Современные технологии в медицине. 2019. Т. 11, № 3. С. 136-145. DOI: https://doi.org/10.17691/stm2019.11.3.17

19. Berg R.D. Translocation of indigenous bacteria from the intestinal tract // Human Intestinal Microflora in Health and Disease. New York : Academic Press, 1983. P. 333-352.

20. Чичерин И.Ю., Погорельский И.П., Лундовских И.А., Дармов И.В., Гаврилов К.Е., Горшков А.С. и др. Транслокация кишечной микробиоты // Журнал международной медицины. Инфекционные заболевания. 2016. № 2 (19). С. 87-99.

21. Никитенко В.И., Копылов В.А., Никитенко М.В. Транслокация бактерий из желудочно-кишечного тракта - естественный защитный механизм. URL: http://bacoren.ucoz.ru/publ/1-1-0-1

22. Zmora N., Soffer E., Elinav E. Transforming medicine with the microbiome // Sci. Transl. Med. 2019. Vol. 11, N 477. Article ID eaaw 1815.

23. Подопригора Г.И., Кафарская Л.И., Байнов Н.А., Шкопоров А.Н. Бактериальная транслокация из кишечника: микробиологические, иммунологические и патофизиологические аспекты // Вестник РАМН. 2015. Т. 70, № 6. С. 640-650.

24. Hase K., Kawano K., Nochi T., Pontes G.S., Fukuda S., Ebisawa M. et al. Uptake through glycoprotein 2 of FimH(+) bacteria by M cells initiates mucosal immune response // Nature. 2009. Vol. 462, N 7270. P. 226-230. DOI: https://doi.org/10.1038/nature08529

25. Ohno H., Hase K. Glycoprotein 2 (GP2): grabbing the FimH bacteria into M cells for mucosal immunity // Gut Microbes. 2010. Vol. 1, N 6. P. 407-410. DOI: https://doi.org/10.4161/gmic.1.6.14078.

26. Тихомиров А.Л., Сарсания С.И. Комплаентность при терапии влагалищных дисбиозов // Медицинский совет. 2019. № 12. С. 146152. DOI: https://doi.org/10.21518/2079-701X-2019-12-146-152

27. Donders G.G. Treatment of bacterial vaginosis: what we have and what we miss // Expert Opin. Pharmacother. 2014. Vol. 15, N 5. P. 645657. PMID: 24579850.

28. McMillan А., Dell M., Zellar M.P., Cribby S. et al. Disruption of urogenital biofilms by lactobacilli // Colloids Surf. B Biointerfaces. 2011. Vol. 86. P. 58-64. DOI: https://doi.org/10.1016/j.colsurfb.2011.03.016

29. Martinez R.C., Seney S.L., Summers K.L. et al. Effect of Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 on the ability of Candida albicans to infect cells and induce inflammation // Microbiol. Immunol. 2009. Vol. 53, N 9. P. 487-495. DOI: https://doi.org/10.1111/j.1348-0421.2009.00154.x

30. Cianci A., Giordano R., Delia A. et al. Efficacy of Lactobacillus Rhamnosus GR-1 and of Lactobacillus Reuteri RC-14 in the treatment and prevention of vaginoses and bacterial vaginitis relapses // Minerva Ginecol. 2008. Vol. 60, N 5. P. 369-376.

31. Kohler G.A., Assefa S., Reid G. Probiotic interference of Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 with the opportunistic fungal pathogen Candida albicans // Infect. Dis. Obstet. Gynecol. 2012. Vol. 2012. Article ID 636474. DOI: https://doi.org/10.1155/2012/63647(46)4

32. Chew S.Y., Cheah Y.K., Seow H.F. et al. Probiotic Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 exhibit strong antifungal effects against vulvovaginal candidiasis-causing Candida glabrata isolates // J. Appl. Microbiol. 2015. Vol. 118, N 5. P. 1180-1190. DOI: https://doi.org/10.1111/jam.12772

33. Ho M., Chang Y.Y., Chang W.C. et al. Oral Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 to reduce Group B Streptococcus colonization in pregnant women: a randomized controlled trial // Taiwan. J. Obstet. Gynecol. 2016. Vol. 55, N 4. P. 515-518. DOI: https://doi.org/10.1016/j.tjog.2016.06.003

34. Евсеев А.А., Пивоварова О.Ю. Комплексная терапия бактериального вагиноза // Здоровье женщины. 2012. № 4 (70): 142-146.

35. Радзинский В.Е., Ордиянц И.М., Апресян С.В. Эффективность коррекции дисбиоза влагалища в I триместре беременности // Российский вестник акушера-гинеколога. 2010. Т. 10, № 3. С. 38-41.

36. Новикова С.В., Логутова Л.С., Игнатьева М.А. Клиническая оценка эффективности и безопасности применения препарата Вагилак для лечения бактериального вагиноза у беременных // Медицинский совет. 2018. № 13. С. 90-94.

37. Кудинов С.В., Суховей Ю.Г., Петров С.А. Эффективность коррекции дисбиоза влагалища пробиотиком "Вагилак" перед радиохирургическим лечением у пациенток с эктопией шейки матки // Журнал акушерства и женских болезней. 2011. № 6. Р. 35-39.

38. Mezzasalma V., Manfrini E., Ferri E., Boccarusso M., Di Gennaro P., Schiano I., Michelotti A., Labra M. Orally administered multispecies probiotic formulations to prevent uro-genital infections: a randomized placebo-controlled pilot study // Arch. Gynecol. Obstet. 2017. Vol. 295, N 1. P. 163-172.

39. 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. Vol. 212, N 5. P. 793-802.

40. Gavriilaki E., Brodsky R.A. Complementopathies and precision medicine // J. Clin. Invest. 2020. Vol. 130. P. 2152.

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