Key Bacteria for Vaginal Health

The microbiota of healthy premenopausal woman is generally dominated by Lactobacillus species, which is an accepted marker of vaginal health and indicates functional host-microbial interactions.


The vulvo-vaginal area has its own distinct commensal microbiome which differs from the other microbiomes in the body. The composition of the microbiome and its dialogue with host immune responses in the vagina plays a role in vaginal, reproductive and maternal health. Dysbiosis of the vaginal flora can play a large role in infertility, frequent miscarriage, endometriosis, pre-term birth, frequent urinary tract infections, bacterial vaginosis, vaginismus and vagino-vulval itching and discomfort.

Key bacteria for vaginal health: Lactobacilli spp.

The species that are present in the vaginal mucosa vary between premenopausal woman and those who have gone through menopause. The microbiota of healthy premenopausal woman is generally dominated by Lactobacillus species, which is an accepted marker of vaginal health and indicates functional host-microbial interactions. The most common Lactobacillus species are L. iners, L. crispatus, L. gasseri, L. jensenii, followed by L. acidophilus, L. fermentum, L. plantarum, L. rhamnosus, L. brevis, L. casei, L. vaginalis, L. delbrueckii, L. salivarius, and L. reuteri (1).

Lactobacilli are extremely important for vaginal health due to their protective and antimicrobial functions. Lactobacilli produce lactic acid, which is a hallmark feature of a ‘normal’ vaginal microbiome, creating an acidic environment (pH 2.8–4.2) that is inhospitable to many non-Lactobacillus commensals and potential vaginal pathogens (2,3). For example, reduced infectivity of Chlamydia trachomatis by L. crispatus, via lactic acid production and acidic pH, has been reported in vitro (4).

Lactic acid also induces autophagy in epithelial cells to degrade intracellular microorganisms and promote homeostasis (5). Additionally, some Lactobacillus species also produce anti-microbial compounds such as bacteriocins that inhibit growth of pathogenic microorganisms such as Candida albicans, Prevotella bivia and Escherichia coli (6).

In addition to their direct role in regulating vaginal health, Lactobacilli also modulate the host immune response, mediated through vaginal epithelial cells (7,8). Lactobacilli are tolerated by vaginal epithelial cells and inhibit induction of pro-inflammatory cytokines such as IL-6, IL-1β and TNF-α (9). Vaginal lactic acid has also been shown to mediate an anti-inflammatory response in the presence of inflammatory-inducing pathogens (10).

Introducing key Lactobacilli

Lactobacillus crispatus

L. crispatus is a high producer of lactic acid and is therefore associated with very acidic vaginal pH. It also produces antimicrobial peptides called bacteriocins, which help maintain homeostasis and prevent pathobiont growth, including BV-associated bacteria (11). Dominance is also linked to increased rates of conception and improved fertility (12).

Lactobacillus gasseri

L. gasseri is another producer of high amounts of lactic acid and anti-microbial peptides (13). L. gasseri produces a bacteriocin called gassericin E, that inhibits growth of BV-associated bacteria including Prevotella bivia, Gardnerella vaginalis, Atopobium vaginae, Mobiluncus mulieris and pathobionts Escherichia coli, Staphylococcus aureus and Streptococcus agalactiae, in vitro (14).

Lactobacillus jensenii

L. jensenii produces moderate-high amounts of lactic acid (15) and produces bacteriocins (13). L. jensenii has been shown to reduce growth and adherence of Gardnenella vaginalis and Prevotella bivia (15) and inhibit growth and hyphae formation of Candida albicans (16).

Lactobacillus iners

L. iners has a unique cell morphology and genome size compared to other Lactobacillus species. Its very small genome is evidence of rapid evolutionary changes, resulting in extensive gene loss. Compared to other Lactobacilli, it is reported to produce moderate levels of lactic acid (17). High levels of L. iners has been detected in women with BV, but also in healthy women (18). High levels have also been detected in women infected with Chlamydia trachomatis (19).

Lactobacillus plantarum

L. plantarum is a lactic acid producer (20) and is able to exhibit strong anti-microbial activity against pathogens including Escherichia coli (21). It is also able to attach to vaginal epithelial cells and significantly reduce the adhesion of Candida albicans. Indeed, it has been proven effective as a potential preventive agent of vulvo-vaginal candidiasis recurrences (22). L. plantarum may also shift the vaginal milieu toward a predominance of Lactobacilli with an improvement of the vaginal pH value (22).

Lactobacillus rhamnosus

L. rhamnosus can modulate the host immune response via TNF-α. A particular strain resulted in over 3,000 gene expression changes when administered to the vagina of premenopausal women and increased expression levels of some anti-microbial defences, similar effects are likely to be seen with other strains (1). It also produces anti-microbial compounds, which have been shown to be effective against BV-associated bacteria and Candida (1).

Conclusions

Lactobacilli are key to orchestrating and maintaining the vaginal ecosystem. Testing the vaginal pH gives an understanding of the acidity, and therefore, an indication of Lactobacilli presence. To delve further, DNA testing such as Female EcologiX gives quantitative measures of different Lactobacilli species, as well as BV-associated bacteria, pathogens and Candida.

The vaginal ecosystem is one of the cornerstones of female and reproductive health. We need to start talking about vaginal health to our patients.

References

  1. Cribby S, Taylor M, Reid G. Vaginal Microbiota and the Use of Probiotics. Interdiscip Perspect Infect Dis. 2008;2008:1–9.
  2. Graver MA, Wade JJ. The role of acidification in the inhibition of Neisseria gonorrhoeae by vaginal lactobacilli during anaerobic growth. Ann Clin Microbiol Antimicrob [Internet]. 2011 Feb 17 [cited 2019 Apr 25];10(1):8. Available from: http://ann-clinmicrob.biomedcentral.com/articles/10.1186/1476-0711-10-8
  3. Amabebe E, Anumba DOC. The Vaginal Microenvironment: The Physiologic Role of Lactobacilli. Front Med [Internet]. 2018;5(June):1–11. Available from: https://www.frontiersin.org/article/10.3389/fmed.2018.00181/full
  4. Nardini P, Ñahui Palomino RA, Parolin C, Laghi L, Foschi C, Cevenini R, et al. Lactobacillus crispatus inhibits the infectivity of Chlamydia trachomatis elementary bodies, in vitro study. Sci Rep [Internet]. 2016 Sep 29 [cited 2019 Apr 15];6(1):29024. Available from: http://www.nature.com/articles/srep29024
  5. Ghadimi D, de Vrese M, Heller KJ, Schrezenmeir J. Lactic acid bacteria enhance autophagic ability of mononuclear phagocytes by increasing Th1 autophagy-promoting cytokine (IFN-γ) and nitric oxide (NO) levels and reducing Th2 autophagy-restraining cytokines (IL-4 and IL-13) in response to Mycobacterium tuberculosis antigen. Int Immunopharmacol [Internet]. 2010 Jun [cited 2019 Apr 15];10(6):694–706. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20381647
  6. Kim J-W, Rajagopal SN. Antibacterial Activities of Lactobacillus crispatus ATCC 33820 and Lactobacillus gasseri ATCC 33323 [Internet]. Vol. 39, The Journal of Microbiology. 2001 [cited 2019 Apr 25]. Available from: https://www.medicatrix.be/download/Lactobacillus.crispatus_anti-bacterien.pdf
  7. Mendling W. Vaginal Microbiota. Adv Exp Med Biol [Internet]. 2016 [cited 2019 Apr 26];902:83–93. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27161352
  8. Aroutcheva A, Gariti D, Simon M, Shott S, Faro J, Simoes JA, et al. Defense factors of vaginal lactobacilli. Am J Obstet Gynecol [Internet]. 2001 Aug [cited 2019 Apr 26];185(2):375–9. Available from: http://www.ncbi.nlm.nih.gov/pubmed/11518895
  9. Aldunate M, Srbinovski D, Hearps AC, Latham CF, Ramsland PA, Gugasyan R, et al. Antimicrobial and immune modulatory effects of lactic acid and short chain fatty acids produced by vaginal microbiota associated with eubiosis and bacterial vaginosis. Front Physiol [Internet]. 2015 Jun 2 [cited 2019 May 21];6:164. Available from: http://journal.frontiersin.org/Article/10.3389/fphys.2015.00164/abstract
  10. Hearps AC, Tyssen D, Srbinovski D, Bayigga L, Diaz DJD, 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 [Internet]. 2017 Nov 12 [cited 2019 Apr 15];10(6):1480–90. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28401934
  11. Donders GGG, Ruban K, Bellen G. Selecting Anti-Microbial Treatment of Aerobic Vaginitis. Curr Infect Dis Rep [Internet]. 2015 May 22 [cited 2019 Apr 15];17(5):24. Available from: http://link.springer.com/10.1007/s11908-015-0477-6
  12. Sirota I, Zarek SM, Segars JH. Potential Influence of the Microbiome on Infertility and Assisted Reproductive Technology. Semin Reprod Med [Internet]. 2014 [cited 2019 Aug 8];32(1):35–42. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4137456/pdf/nihms-618907.pdf
  13. Kovachev S. Defence factors of vaginal lactobacilli. Crit Rev Microbiol [Internet]. 2018 Jan 2 [cited 2019 Apr 15];44(1):31–9. Available from: https://www.tandfonline.com/doi/full/10.1080/1040841X.2017.1306688
  14. Maldonado-Barragán A, Caballero-Guerrero B, Martín V, Ruiz-Barba JL, Rodríguez JM. Purification and genetic characterization of gassericin E, a novel co-culture inducible bacteriocin from Lactobacillus gasseri EV1461 isolated from the vagina of a healthy woman. BMC Microbiol [Internet]. 2016 Dec 12 [cited 2019 Apr 17];16(1):37. Available from: http://www.biomedcentral.com/1471-2180/16/37
  15. Atassi F, Brassart D, Grob P, Graf F, Servin AL. Lactobacillus strains isolated from the vaginal microbiota of healthy women inhibit Prevotella bivia and Gardnerella vaginalis in coculture and cell culture. FEMS Immunol Med Microbiol [Internet]. 2006 Dec 1 [cited 2019 Apr 17];48(3):424–32. Available from: https://academic.oup.com/femspd/article-lookup/doi/10.1111/j.1574-695X.2006.00162.x
  16. Wang S, Wang Q, Yang E, Yan L, Li T, Zhuang H. Antimicrobial Compounds Produced by Vaginal Lactobacillus crispatus Are Able to Strongly Inhibit Candida albicans Growth, Hyphal Formation and Regulate Virulence-related Gene Expressions. Front Microbiol [Internet]. 2017 Apr 4 [cited 2019 Apr 25];08:564. Available from: http://journal.frontiersin.org/article/10.3389/fmicb.2017.00564/full
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  18. Srinivasan S, Hoffman NG, Morgan MT, Matsen FA, Fiedler TL, Hall RW, et al. Bacterial Communities in Women with Bacterial Vaginosis: High Resolution Phylogenetic Analyses Reveal Relationships of Microbiota to Clinical Criteria. Ratner AJ, editor. PLoS One [Internet]. 2012 Jun 18 [cited 2019 Apr 17];7(6):e37818. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22719852
  19. Parolin C, Frisco G, Foschi C, Giordani B, Salvo M, Vitali B, et al. Lactobacillus crispatus BC5 Interferes With Chlamydia trachomatis Infectivity Through Integrin Modulation in Cervical Cells. Front Microbiol [Internet]. 2018 [cited 2019 Apr 25];9:2630. Available from: http://www.ncbi.nlm.nih.gov/pubmed/30459737
  20. Fu W, Mathews AP. Lactic acid production from lactose by Lactobacillus plantarum: Kinetic model and effects of pH, substrate, and oxygen. Biochem Eng J. 1999;3(3):163–70
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  22. De Seta F, Parazzini F, De Leo R, Banco R, Maso GP, De Santo D, et al. Lactobacillus plantarum P17630 for preventing Candida vaginitis recurrence: A retrospective comparative study. Eur J Obstet Gynecol Reprod Biol [Internet]. 2014;182:136–9. Available from: http://dx.doi.org/10.1016/j.ejogrb.2014.09.018

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