Magnifying into our body: The vaginal microbiota

By Kai Yee Eng

There are a huge number of microorganisms living in and on our bodies. If we look into bacteria only, it is estimated that there are 3.8∙1013 bacteria with a reference man of 70kg, nearly a 1:1 ratio to human cells (~3.0∙1013).1 Although they only accounts for approximately 0.2kg weight1, their significance has been underestimated until recent years. The launch of Human Microbiome Project, currently completed phase 2, has discovered some roles of the microbiota which could have contributed to the maintenance of health and their associations or relationships with various diseases.2,3 On our skin, in our oral cavity, in our gut, these tiny little creatures form colonisations and many research has been working on these communities. The vagina is also one of the homes to these microorganisms and a key research area. 

The vaginal microbiota forms a mutualistic relationship with the host. The host provides nutrients and space to support the growth of the microbiota, while the vaginal microbiota interacts with the host to provide benefits such as protection against infections. A healthy vaginal microbiota in the reproductive age is dominated by anaerobes Lactobacillus spp.  The main role of Lactobacillus spp. is believed to be the production of lactic acid, after metabolising glycogen.4 This creates a low pH of 3.8-4.4.5 Besides, lactic acid acts as an inhibitor to histone deacetylase6 , thus increasing the acetylation and expose the DNA to be more readily for gene transcription. Furthermore, the intracellular lactic acid increases the activity of autophagy.4 This is important as autophagy degrades non-functional proteins due to oxidative stress as well as pathogens.7

Across different ages of an individual, the vaginal microbiota fluctuates and changes depending on physiological changes. It is thought that the vaginal microbiota was initially acquired from mother’s microbiota upon labour.8 As puberty hits, the reproductive system matures, and the hormones changes regularly corresponding to menstrual cycle. This shifts the microbiota from E. coli and Staphylococci to Lactobacillus spp.9 The diversity of the vaginal microbiota has also observed a drastic change from Prevotella, Finegoldia, Peptoniphilus, Anaerococcus, Dialister, and Lactobacillus to Lactobacillus dominance in later stage of puberty.10 It is also noted that the discharge of menses, changes the microenvironment,  increasing the pH to the normal blood level pH while providing iron from the blood.10 This would result in temporal microbiota bloom. 

Likewise, in menopause, the decrease of oestrogen level results in the decrease of Lactobacillus spp.  and an increase of E.coli.11 This is also associated with an increase of pH level in the vaginal ecosystem, due to the lack of lactic acid-producing bacteria. As a continuation of this factor, the vaginal microbiota of a pregnant women differs from the non-pregnant women as well, in which oestrogen continuously increases until the trimester. Besides Lactobacillus spp, which is a key component of a healthy vaginal microbiota, Actinomycetales, Clostridiales, and Bacteroidales form the less diversified pregnant vaginal microbiome. Less mollicutes, a class of primitive bacteria without cell wall and minimal genome are also observed in pregnant women.12,13 As a contrary, Actinobacteria, Prevotella, Veillonellaceae, Streptococcus, Proteobacteria, Bifidobacteriaceae, Bacteroides, and Burkholderiales are found in non-pregnant women.

Surprisingly, epidemiology studies have revealed that ethnicity also plays a role in determining the vaginal microbiota. There are at least five different compositions recognised as community state types (CST). CST I, II III and V are characterised with a majority of Lactobacillus crispatus, Lactobacillus iners, Lactobacillus gasseri and Lactobacillus jensenii respectively.9,14 CST II is commonly found in white or Caucasian women, CST I in Asian women, and lastly CST V in black and Hispanic women.5 CST IV on the other hand, is a mixture of different anaerobes and strictly anaerobes, which is also commonly observed in bacterial vaginosis. Lastly, other than the above factors mentioned, antibiotics prescription and sexual activities may cause disruption to the balanced vaginal microbiota.5,15 

One of the known medical condition due to dysbiosis of vaginal microbiota is bacterial vaginosis. Although 50% of patients may not experience any symptom16 , it is a risk factor of preterm birth, pelvic inflammatory diseases and sexually transmitted diseases.17 Unlike the gut microbiota which the dysbiosis normally reflects a reduction of diversity, the increase in diversity of vaginal microbiota, with a reduction of Lactobacillus spp. and increase of facultative and obligate anaerobes, contributes to bacterial vaginosis. Gardnerella vaginalis and Mycoplasma hominis and other anaerobes from Prevotella, Porphyromonas, Bacteroides and Peptostreptococcus species are found in bacterial vaginosis patients.18 These bacteria contribute to the increase of pH level in the vaginal mucous and leads to the arise of “clue cells”, a classic clinical manifestation of bacterial vaginosis.18, 19 While the bacteria may seem to be the cause behind the disease, it is not always the case. Clinical study on pre-menarch females has observed the growth of Gardnerella vaginalis or its dominance at a certain time point, and this is not due to any sexual activity which is also another factor to changing microbiota composition.20 

Current research foresees a great opportunity in harvesting the microbiome to improve female health. While multi-omics studies and sequencing such as Human Microbiome Project has been carried out over the past decades, we currently know too less about the vaginal microbiota. More research is expected in order to understand this community for example how the gut and oral microbiota affects the composition of vaginal microbiota. With this fundamental research, there would be a day we would harness the beauty of this mutualistic relationship and translate it into clinical practice, to aid in diagnosis and personalised treatment. It is now time to magnify into our body, to the microbiome. 

References:

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6. Latham T, MacKay L, Sproul D, Karim M, Culley J, Harrison DJ, et al. Lactate, a product of glycolytic metabolism, inhibits histone deacetylase activity and promotes changes in gene expression. Nucleic Acids Res [Internet]. 2012 Jun [cited 2021 Nov 8];40(11):4794. Available from: /pmc/articles/PMC3367171/

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8. Moosa Y, Kwon D, de Oliveira T, Wong EB. Determinants of Vaginal Microbiota Composition. Front Cell Infect Microbiol. 2020 Sep 2;10:467. 

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11. Muhleisen AL, Herbst-Kralovetz MM. Menopause and the Vaginal Microbiome. 2016 [cited 2021 Nov 9]; Available from: http://dx.doi.org/doi:10.1016/j.maturitas.2016.05.015http://dx.doi.org/10.1016/j.maturitas.2016.05.015

12. Freitas AC, Chaban B, Bocking A, Rocco M, Yang S, Hill JE, et al. The vaginal microbiome of pregnant women is less rich and diverse, with lower prevalence of Mollicutes, compared to non-pregnant women. Sci Reports 2017 71 [Internet]. 2017 Aug 23 [cited 2021 Nov 9];7(1):1–16. Available from: https://www.nature.com/articles/s41598-017-07790-9

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15. Ma B, Forney LJ, Ravel J. Vaginal Microbiome: Rethinking Health and Disease. Annu Rev Microbiol [Internet]. 2012 [cited 2021 Nov 7];66:371–89. Available from: http://www.annualreviews.org

16. Bacterial vaginosis – NHS [Internet]. [cited 2021 Nov 8]. Available from: https://www.nhs.uk/conditions/bacterial-vaginosis/

17. Bacterial vaginosis – Symptoms and causes – Mayo Clinic [Internet]. [cited 2021 Nov 8]. Available from: https://www.mayoclinic.org/diseases-conditions/bacterial-vaginosis/symptoms-causes/syc-20352279

18. Sobel JD. Bacterial Vaginosis. https://doi.org/101146/annurev.med511349 [Internet]. 2003 Nov 28 [cited 2021 Nov 8];51:349–56. Available from: https://www.annualreviews.org/doi/abs/10.1146/annurev.med.51.1.349

19. Chen X, Lu Y, Chen T, Li R. The Female Vaginal Microbiome in Health and Bacterial Vaginosis. Front Cell Infect Microbiol. 2021 Apr 7;11:271. 

20. Hickey RJ, Zhou X, Settles ML, Erb J, Malone K, Hansmann MA, et al. Vaginal Microbiota of Adolescent Girls Prior to the Onset of Menarche Resemble Those of Reproductive-Age Women. MBio [Internet]. 2015 Mar 24 [cited 2021 Nov 8];6(2). Available from: /pmc/articles/PMC4453513/

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