The vaginal microbiome in health and disease: review of current evidence

The human body is home to a vast number of microorganisms, collectively known as the human microbiome. While much of the research on the human microbiome has focused on the gut, there are multiple other sites in the body where microbes play an important role. Among these, the vaginal microbiome has been the focus of increased interest over recent years.

Much like the gut microbiome, the human vagina is inhabited by different species of bacteria, viruses, archaea, fungi, and protozoa. However, the vaginal microbiome is unique in the low diversity it harbours¹. In healthy people, the vaginal microbiome is dominated by bacteria of the genus Lactobacillus. It is estimated that more than 70% of the human vaginal microbiome is composed of this bacterium². Research studies have also shown a link between health and the composition of the vaginal microbiome. For example, a low abundance of Lactobacilli is associated with an increased risk of different vaginal infections³, such as aerobic vaginitis, bacterial vaginosis (BV) or candidiasis.

While the mechanisms driving the influence of Lactobacilli on health are still being studied, research suggests that a key property of these bacteria is the production of lactic acid. The idea is that Lactobacilli produce lactic acid, creating an acidic microenvironment that prevents the overgrowth of potentially harmful bacteria.

Multiple factors, including ethnicity, health status, hormonal levels, antibiotic use, and age, influence the composition of the vaginal microbiome. These factors also interact among themselves, ultimately influencing the composition of the vaginal microbiome and women’s health.

Maintaining an optimal composition of the vaginal microbiome may help women avoid vaginal dysbiosis and associated infections throughout their lifetime. The use of antibiotics and antifungal medicines are commonly prescribed under the standard medical approach to treat BV and candidiasis. Still, these treatments are not always optimal, as bacteria and fungi may be able to resist them through the formation of biofilms or the development of resistance. In addition, antibiotics may affect native Lactobacilli and ultimately promote conditions like BV and candidiasis.

More effective and natural solutions for maintaining a healthy vaginal microbiome are needed and are the subject of research. Probiotics, for example, are leading candidates that may serve as an intervention to help restore and maintain a healthy vaginal microbiome.

At AUSCFM, we are on top of the current research involving the vaginal microbiome and consider novel, evidence-based treatments. We employ leading diagnostic testing and apply a comprehensive approach for the treatment of vaginal infections, being mindful of the importance of restoring and maintaining the vaginal microbiome diversity.

What is the vaginal microbiome?

The vaginal microbiome generally refers to the large community of microorganisms that inhabit the female genital tract, adapted to living within their human host without causing harm. The female genital tract (FGT) can be generally divided into the vaginal canal, the cervix and the uterus⁴. The composition of the FGT microbiome differs between the lower and upper portions of the vaginal tract. The lower portion of the FGT (cervix and vagina) has an estimated bacterial load 102-104 fold higher than the bacterial load in the upper part of the FGT (uterus and fallopian tubes).

The FGT microbiome is generally composed of a wide range of different microorganisms, but members of the bacterial genus Lactobacillus are the dominant group, at least in healthy women. FGT microbiomes dominated by non-Lactobacillus species are usually associated with poor health and high levels of inflammation⁴.

Each woman has a unique vaginal microbiome composition, which fluctuates over time and is affected by factors like diet, lifestyle, hormones, genetics, and age. The most common (and best-studied) microorganisms of the VMB are bacteria and fungi. Among these, bacteria are the most common, and within bacteria, Lactobacilli represent about 70% of the VMB.

Types of vaginal microbiome

Among women of reproductive age, genetic studies have identified five different microbial compositions of the vaginal microbiome, each dominated by a unique species of Lactobacillus. Women usually have one of these four compositions, known as community state types or CST:

These groups represent bacterial compositions found in about 90% of women. The fifth CST, called CST IV, is a complex mixture of bacteria and is not dominated by any one species. Some of the bacterial members of CST IV include Gardnerella, Atopobium, Prevotella, Candidatus, Lachnocurva vaginae, Sneathia, Peptoniphilus, Finegoldia and Megasphaera.

CST I, III and V are associated with a healthy vaginal microbiome, whereas CST IV is more often associated with certain medical conditions, such as aerobic vaginitis or bacterial vaginosis (BV). CST III has been associated with both health, microbial dysbiosis, and BV.

The vaginal microbiome also includes non-bacterial species, such as fungi. However, the structure and role of vaginal fungi (also known as vaginal mycobiota) is still under study, and it is not as well understood as bacteria. So far, it is known that vaginal mycobiota is composed of members of Ascomycota or Basidiomycota, two broad groups (aka Phylum) of fungi.

Key factors driving VMB composition

The vaginal microbiome is shaped by multiple factors, including age, ethnicity, physiological factors, menstrual, the immune system, vaginal infections, certain medications and probiotics, lifestyle and diet.

Among all these factors, age arguably is amongst the most important drivers of the vaginal microbiome.

Age – VMB changes across childhood, puberty, adulthood, pregnancy, menopause and post-menopause.
Ethnicity – certain ethnic groups, like Black, African-American or Hispanic, have a VMB dominated with diverse species, including some associated with BV. In contrast, lactobacilli dominate the VMB among Asian and White women.
Menstrual cycle – estrogen levels have been associated with specific VMB composition.
Lifestyle – certain personal hygiene practices (i.e., vaginal douching, use of soaps, type of underwear, menstrual protection, and sprays) can affect VMB composition.
Infections and disease – certain antibiotics and antifungal medicines can significantly affect VMB composition.
Immune function – Altered immune function can affect how immune cells interact with VMB.
Probiotics – the use of specific probiotic supplements can affect the VMB composition.

Connecting the immune system with the vaginal microbiome

The immune system strongly influences the composition of the vaginal microbiome. Immune cells found in the vaginal mucosa both interact and modulate the composition of the vaginal microbiota. This link between immune cells and vaginal microbiota is complex and involved epithelial and immune cells, antimicrobial peptides, pro/anti-inflammatory cytokines/chemokines, and secretory antibodies. Immune cells help maintain homeostasis with the microbial population of the vagina while also fencing off invading pathogens.

Due to this link between immunity and vaginal microbes, any alteration to the normal composition of the vaginal microbiota can result in immune responses. For example, when the vaginal microbiota experiences a reduced level of lactobacilli, overgrowth of pathogens may occur, leading to immune responses¹.

Focus on age

The composition of the vaginal microbiome changes significantly with age, from childhood to puberty, during reproduction and pregnancy, and beyond. Even throughout the transition period to menopause and after menopause, the vaginal microbiome is changing. Some key aspects of this process include:

During childhood, the vaginal microbiome is dominated by Gram-positive anaerobic bacteria, Gram-negative anaerobic bacteria and aerobic bacteria.
During pre-puberty, the vaginal microbiome is characterised low abundance of lactobacilli, Gardnerella vaginalis, and Prevotella bivia in the vaginal tract.
During puberty, when estrogen levels increase, the vaginal microbiome resembles that of adult women, dominated by Lactobacillus crispatus, Lactobacillus gasseri, Lactobacillus iners, and Lactobacillus jensenii.
Research comparing the vaginal microbiome composition between pregnant and non-pregnant women has found significant changes during pregnancy. Lactobacilli dominance seems to increase throughout pregnancy, along with decreased dominance of bacteria associated with bacterial vaginosis.
- In pregnant women, low levels of lactobacilli have been linked to adverse outcomes during delivery, such as pre-term delivery or miscarriages^4-5.
During menopause, the vaginal microbiome is dominated by bacterial species from genera Lactobacillus, Gardnerella, Prevotella, and Atopobium, with overall levels of Lactobacillus being lower, compared to pre-menopause.

The vaginal microbiome and health

Multiple studies have reported associations between the composition of the vaginal microbiome and certain health problems². Some key findings of these studies include:

Acquisition of sexually transmitted diseases (STI), such as HIV, gonorrhoea, chlamydia, trichomonas, HSV, HPV and syphilis, seem associated with levels of Lactobacillus. Generally, studies found that the presence or increased relative abundance of Lactobacillus is associated with decreased risk of acquiring an STI.
Urinary tract infections seem more common in women with low levels of Lactobacillus and high levels of E. coli.
Pelvic inflammatory disease seems to occur more often in women with higher bacteria levels associated with bacterial vaginosis.
Preterm delivery shows an association with levels of Lactobacillus. Increased relative abundance of Lactobacillus seems to be associated with decreased risk of preterm delivery.

What is a healthy vaginal microbiome?

There is no specific composition of microorganisms that can be considered a healthy vaginal microbiome. Instead, the specific composition of this microbiome changes from woman to woman.

However, a vaginal microbiome dominated by Lactobacillus has consistently been identified as key to a healthy microbiome, as it offers a greater degree of infection protection than a more diverse vaginal microbiome.

Likewise, a vaginal microbiome with a low proportion of Lactobacillus and a high proportion of facultative and obligate anaerobic bacteria (such as Gardnerella, Prevotella, Atopobium and Sneathia) can be considered non-optimal. Such sub-optimal vaginal microbiome has been associated with an increased risk of acquiring and transmitting STIs, higher Incidence and prevalence of the human papillomavirus and increased risk of cervical cancer, among other problems.

Keeping a healthy vaginal microbiome

Among the many factors affecting the composition of the vaginal microbiome, some are called modifiable, and others non-modifiable. Non-modifiable factors include genetics or ethnicity, as well as age or immune function (when this has a genetic basis). In contrast, modifiable factors include diet, certain lifestyle factors and probiotics. These factors can be altered to favour the formation and maintenance of a healthy vaginal microbiome. Among these factors, some examples include¹:

Personal hygiene practices – vaginal douching, use of soaps, type of underwear, menstrual protection, and sprays can directly affect the composition of the vaginal microbiome.
- According to studies, vaginal douching has the strongest association with an increased risk of BV/vaginal dysbiosis compared to other hygiene practices.
Having multiple sexual partners is associated with lactobacilli depletion and an increased risk of bacterial vaginosis.
Smoking is a well-known factor that has been shown to increase the risk of vaginal dysbiosis and bacterial vaginosis.
Microbes from different sources can influence the vaginal microbiome. This includes microbes from the gut microbiome, sexually transmitted infections, or from opportunistic bacteria, fungi and pathogens.
Chronic psychosocial stress can influence the balance in the vaginal lactobacilli.
Following a healthy diet, low in fat, rich in nutrients, and low glycemic index is associated with a lower risk of bacterial vaginosis.

Other factors, including urbanisation and a woman’s education level, are still under study. One study, for example, found that women aged 25–45 with higher education levels had more often Lactobacillus-dominated vaginal microbiome compared to women with less education⁶.

In addition to modifiable factors, probiotics may help improve the composition of the vaginal microbiome. Probiotics are live microorganisms that may confer a health benefit when consumed in adequate amounts. Some studies show that certain probiotic strains containing commonly are effective at increasing levels of vaginal lactobacilli.

While these probiotic supplements are available in Australia, any patient wanting to try such probiotic supplements should consult a health care practitioner first.

Finally, a potential treatment currently under study is vaginal microbiome transplantation. In one study, women with bacterial vaginosis achieved long-term remission after 5–12 months of vaginal microbiome transplantation from healthy donors⁷.

Focus on vaginal infections and gut dysbiosis

An emerging concept is the “gut-vagina axis”, which highlights the important interaction between the gut microbiota and the microbes living in the vagina. Supporting the importance of this interaction, recent studies suggest that following a healthy diet rich in nutrients, low glycemic index, and lower fat intake can reduce the risk of developing bacterial vaginosis^8-9. Other studies have shown that following a diet rich in betaine is associated with higher levels of vaginal Lactobacillus, which is found in healthy people. Another study found that women who are obese or overweight are more likely to develop bacterial vaginosis. At the heart of this correlation, researchers think that being above your optimal weight may be associated with dysfunction/disturbances in host metabolism, as well as in hormone levels and immune function. Obesity is also associated with dysbiosis of the gut microbiome composition, which can affect the composition of the vaginal microbiome (Reviewed in Reference 1).

The findings of these studies hint at the importance of maintaining a healthy gut and gut microbiome to have a healthy vaginal microbiome.

Fungi and vaginal health

Relative to bacterial, the role of fungi in the vaginal environment is less understood. So far, it is well established that the diversity of fungal species in the vagina is lower than that of bacteria. The community of fungi living in the vagina is commonly known as the vaginal mycobiota, mainly composed of two groups of fungi: Ascomycota and Basidiomycota. Among these groups, the most common fungi found in the vagina belong to a handful of genera, such as Candida, Cladosporium, Pichia, Aspergillus, and Rhodotorula. Overgrowth of any of these species may cause disease. For example, among these genera, overgrowth of Candida albicans is a common cause of vulvovaginal candidiasis.

Probiotics and vaginal health

Probiotics are defined as “live microorganisms that, when administered in adequate amounts, confer a health benefit on the host”. An increasing number of studies support the notion that probiotic supplementations, particularly of lactobacilli, increase levels of vaginal lactobacilli in healthy women or women with bacterial vaginosis and/or vulvovaginal candidiasis. Probiotics have also been shown to promote a healthy composition of the vaginal microbiome during and after recovery from antibiotics/antifungal treatment.

The potential benefits of probiotics on vaginal health are currently under study, but studies suggest potential mechanisms:

Probiotics can increase levels of lactic acid and hydrogen peroxide, which can lower vaginal pH.
Probiotics may produce antimicrobial compounds, which can stimulate the immune system and help maintain bacterial balance.
Probiotics may also have a role in inhibiting the attachment of pathogenic bacteria and consume the same nutrients as pathogens, restricting their growth.

Functional Medicine and vaginal health

So far, we know that the vaginal microbiome plays an important role in various aspects of women’s health. The composition of this microbiome changes across the lifespan and is influenced by multiple factors, but it remains clear that a healthy vaginal microbiome requires a community dominated by lactobacilli. While further research is needed, there is significant evidence supporting a protective role for lactobacilli, including protection against STIs and other ailments.

Improving and maintaining a healthy vaginal microbiome will likely require different approaches. Among these, diet and personal hygiene (vaginal douching in particular) play important roles.

At AUSCFM, we follow a modern and evidence-based approach to diagnosing and treating pathologies associated with the female reproductive tract. At the heart of our approach, we employ advanced testing to detect evidence of microbial imbalances. Our vaginal microbiome test, for example, measures levels of more than a dozen potentially harmful bacteria, sexually transmitted pathogens, five different species of Candida (the most common vaginal fungi) and measures levels of beneficial bacteria.

Based on our advanced microbiome testing results, we can identify evidence of dysbiosis (imbalances in the microbial composition). In addition to vaginal microbiome health, we employ advanced testing that targets six specific gut pathologies. Taken together, the results of these seven tests will give us a comprehensive view of the factors influencing a patient’s health and will help us design personalised treatment strategies.

We may employ standard approaches for treating infections and other pathologies depending on each patient. In addition, we also consider and employ novel, evidence-based approaches that are guaranteed to improve a patient’s health. For example, we regularly employ vaginal probiotic suppositories that enrich the natural vaginal flora. So far, we have obtained outstanding results, with patients experiencing significant improvements in their vaginal health.

To learn more about the seven pathologies we target, take the first step towards a healthier life and

References

Lehtoranta, L., Ala-Jaakkola, R., Laitila, A., & Maukonen, J. (2022). Healthy Vaginal Microbiome and Influence of Probiotics Across the Female Life Span. Frontiers in Microbiology, 787.
France, M., Alizadeh, M., Brown, S., Ma, B., & Ravel, J. (2022). Towards a deeper understanding of the vaginal microbiome. Nature Microbiology, 7(3), 367-378.
Ameen, F., Moslem, M., Al Tami, M., Al-Ajlan, H., and Al-Qahtani, N. (2017). Identification of Candida species in vaginal flora using conventional and molecular methods. J. Mycol. Med. 27, 364–368. doi: 10.1016/j.mycmed.2017.04.105
Plesniarski, A., Siddik, A. B., & Su, R. C. (2021). The Microbiome as a Key Regulator of Female Genital Tract Barrier Function. Frontiers in Cellular and Infection Microbiology, 1292.
Al-Memar, M., Bobdiwala, S., Fourie, H., Mannino, R., Lee, Y. S., Smith, A., et al. (2020). The association between vaginal bacterial composition and miscarriage: a nested case-control study. BJOG 127, 264–274. doi: 10.1111/1471-0528.15972
Virtanen, S., Rantsi, T., Virtanen, A., Kervinen, K., Nieminen, P., Kalliala, I., et al. (2019). Vaginal microbiome composition correlates with pap smear microscopy and next-generation sequencing and is socioeconomic status. Rep. 9:7750. doi: 10.1038/s41598-019-44157-8
Lev-Sagie, A., Goldman-Wohl, D., Cohen, Y., Dori-Bachash, M., Leshem, A., Mor, U., et al. (2019). Vaginal microbiome transplantation in women with intractable bacterial vaginosis. Med. 25, 1500–1504. doi: 10.1038/s41591-019-0600-6
Thoma, M. E., Klebanoff, M. A., Rovner, A. J., Nansel, T. R., Neggers, Y., Andrews, W. W., et al. (2011b). Bacterial vaginosis is associated with variation in dietary indices. J. Nutr. 141, 1698–1704. doi: 10.3945/jn.111.140541
Tuddenham, S., Ghanem, K. G., Caulfield, L. E., Rovner, A. J., Robinson, C., Shivakoti, R., et al. (2019). Associations between dietary micronutrient intake and molecular-Bacterial Vaginosis. Reprod. Health 16:151. doi: 10.1186/s12978-019-0814-6