Bacterial Vaginosis: A Dysbiosis of the Vaginal Microbiome
It is no secret that women’s health research is severely unrepresented in today’s vast collection of medical/heath research, in part due to the difficulties of obtaining reliable data on women, due to various confounding variables, such as hormonal fluctuations, stage of menstrual cycle, and our inability to measure synthetic hormones in the blood (applicable to women on oral contraceptives). However, this is no excuse for the fact that up to one-third of women of reproductive age experience bacterial vaginosis (BV), and the commonly prescribed treatments (metronidazole and clindamycin) lead to high rates of recurrence (>50%) within months of treatment, eventually giving way to a diagnosis of “chronic” BV.² These drugs also inflict damage on the endogenous Lactobacilli in the vagina, contributing to an unstable vaginal environment that is susceptible to further dysbiosis and BV recurrence. Thankfully, emerging research is shedding light on new probiotic therapies that hold potential in long-term stabilization of the vaginal microbiota (VMB) by increasing the abundance of Lactobacilli.
What is bacterial vaginosis?
Bacterial vaginosis is a condition that occurs when there is a decrease in Lactobacillus in the vagina, and there is an 100-1000 fold increase in anaerobic bacteria from genera such as Gardnerella, Prevotella, Dialister, Megasphaera, Atopobium, Mobiluncus, and Peptoniphilus.³ The overgrowth of anaerobic bacteria increases the vaginal pH, making the vagina less acidic than ideal and contributing to an unstable and pro-inflammatory environment. When the composition of the VMB is imbalanced and unstable, as seen in BV, this is known as dysbiosis, and it is a deviation from eubiosis. BV can present with symptoms or asymptomatically, and it can be difficult to treat due to the ability of G. vaginalis (a species seen in BV) to form a polymicrobial biofilm that can resist antibiotics and tolerate the endogenous production of lactic acid.³
What does a healthy vaginal microbiota look like?
The average vaginal microbiota contains billions of bacteria, ideally consisting of a large abundance of Lactobacilli (L. crispatus, L. gassers, L. infers, L. jenseii).¹ The vaginal microbiota is often classified into five community state types (CSTs), depending on which species of Lactobacillus is dominant, CST-IV being characterized by a lack of Lactobacillus dominance and known for its instability and disruptive nature. Whereas the gut microbiota thrives when there is a wide diversity of microbial species, the vaginal microbiota prefers a dominance of Lactobacillus, ideally L. crispatus, which has been shown to create the most stable VMB.² Lactobacillus produces lactic acid, which maintains the low pH & acidity of an ideal vaginal environment. It also secretes bacteriocins, which help to prevent the inhabitation of unwelcome microbes, such as the anaerobic bacteria seen in BV.³ In order to produce lactic acid, Lactobacillus utilizes glycogen stores in the epithelial cells of the vagina. Higher levels of estrogen increase glycogen storage in the vagina (and thus Lactobacilli and lactic acid), which is a possible explanation as to why higher levels of estrogen are also associated with a lower risk of BV. Therefore, it makes sense that pregnancy is associated with a more stable VMB, and menopause is a risk factor for BV, as well as the stage of one’s menstrual cycle (less stable during menstruation).
Why should I care about BV? What are the consequences of BV?
BV is linked to a variety of negative health outcomes. There is a positive correlation between elevated pH (as seen in BV) and cancer biomarkers, as well as a negative correlation between Lactobacillus abundance and cancer biomarkers.¹ BV is also associated with an increased risk of STDs, such as HPV, HIV, herpes, chlamydia, and gonorrhea.² Studies have shown that women who had pre-term births were more likely to have lower levels of L. crispatus and higher levels of anaerobic bacteria associated with BV.² Similarly, an increase in G. vaginalis leads to an increased risk of infertility.² BV and a low abundance of Lactobacillus is also associated with an increase in pro-inflammatory cytokines (TNFalpha and a variety of pro-inflammatory interleukins).³ Conversely, L. crispatus has been associated with an increase in fertility and a decrease in pro-inflammatory cytokines.³
What increases my risk of BV?
The act of douching increases one’s risk of bacterial vaginosis.² Douching can disrupt the vaginal microbiota, especially CSTs that are already prone to instability and dysbiosis.
Smoking may also increase one’s risk of BV due to the estrogen-lowering effects of nicotine.² Lower levels of circulating estrogen may lead to a lower accumulation of glycogen in the vaginal epithelial cells, starving Lactobacilli of their fuel source, depleting the vagina of lactic acid and increasing the pH, fostering an environment that allows anaerobic bacteria to flourish.
Stress and its role in increased cortisol production takes a toll on the vaginal environment. Not only does stress suppress immune system functioning, but it also inhibits the accumulation of glycogen in the vagina.² Like smoking, this leads to decreased Lactobacilli, decreased acidity, and a greater risk of BV.
Although the direct effects of the gut microbiota on the VMB are still being studied, the systemic inflammation and immune system dysfunction created by a gut dysbiosis can negatively impact all systems of the body, including the vagina, especially considering the emerging knowledge of the gut-vagina axis.¹
As mentioned early, specific hormonal fluctuations are risk factors for BV. For instance, menopause is caused by a drop in estrogen levels. Decreased Lactobacilli and increased pH can be downstream consequences of the lower estrogen levels seen in menopause, which can allow the growth of harmful species of bacteria in the vagina. Therefore, the higher levels of estrogen seen in pregnancy can create a more stable VMB, as seen in several studies.² Even within a menstrual cycle, there can be VMB composition changes, specifically an increase in G. vaginalis and a decrease in L. crispatus during menstruation.³ The least VMB composition changes are seen in vaginas with an abundance of L. crispatus, which is known for its stabilizing and protective properties in the vagina.
What are the treatments?
The current treatments for bacterial vaginosis are metronidazole and clindamycin, both of which are antibiotics. The recurrence rate of BV when treated with antibiotics is greater than 50%, and it is thought that this is due to acquired resistance, persisting biofilms, and/or damage to endogenous and beneficial Lactobacilli.³ Curing BV requires a restoration of a stable VMB.
Probiotics are an appealing treatment because they do not cause damage to beneficial species of Lactobacillus. They may even increase the abundance of Lactobacilli and promote a more stable VMB that has increased lactic acid and bacteriocin production and an increased pH, thereby inhibiting the continued growth of anaerobic species by creating an environment where they cannot survive, thus preventing the return of BV-associated microbes and the recurrence of BV.
The Future of BV Treatment: Probiotics and Microbiota/Lactobacillus Support
Both oral and intravaginal probiotics have been shown to be effective in treating BV, often with significantly lower rates of recurrence.² Despite oral probiotics having to go through the digestive tract, evidence shows they have an influence on the VMB composition.¹ This probiotic influence might be even quicker with intravaginal probiotics.¹ Even if probiotics are unable to permanently alter the VMB composition, their antimicrobial and immuno-modulatory effects are still positive and stabilizing.
Vaginal microbiota transplant (VMT) (similar to fecal microbiota transplant (FMT)) may also be a treatment option in the future. One study found an 80% long-term remission rate, as well as a Lactobacillus dominant VMB, following VMT treatment.¹
Although more studies are needed to determine how to most effectively use probiotics to treat BV, current research points to a promising potential of probiotics to treat the condition and prevent recurrence. There is little doubt that an abundance of L. crispatus (which may be achieved through probiotics) leads to a stabilized VMB. Bacterial vaginosis afflicts far too many women and is linked to too many adverse health outcomes to not pursue safer, more effective treatments.
References
Amabebe E, Anumba DOC. Female gut and genital tract Microbiota-induced crosstalk and differential effects of short-chain fatty acids on immune sequelae. Front Immunol [Internet]. 2020;11:2184. Available from: http://dx.doi.org/10.3389/fimmu.2020.02184
Lehtoranta L, Ala-Jaakkola R, Laitila A, Maukonen J. Healthy vaginal Microbiota and influence of probiotics across the female life span. Front Microbiol [Internet]. 2022;13:819958. Available from: http://dx.doi.org/10.3389/fmicb.2022.819958
Chen X, Lu Y, Chen T, Li R. The female vaginal microbiome in health and bacterial vaginosis. Front Cell Infect Microbiol [Internet]. 2021;11:631972. Available from: http://dx.doi.org/10.3389/fcimb.2021.631972