Factors Influencing the Vaginal Microbiome

Other exogenous factors influence vaginal health and should be examined as they may play a significant role in influencing reproductive health outcomes and themselves may be associated with microbiome composition. In the United States, differences in health outcomes for groups defined by race/ethnicity are oftentimes confounded by inter-group differences in socioeconomic status, social determinants of health, and health behaviors linked to social determinants of health. The following sections will explore how vaginal hygiene practices, diet, sexual partners and practices, gender affirming treatments, stress, and social determinants impact the vaginal microbiome.

Douching and Hygiene Practices

The vagina is colloquially referred to as a “self-cleaning oven” because of its ability to maintain its cleanliness and health independent of the use of soaps or human-made cleansers. Despite this, the feminine hygiene market is a $1.1 billion dollar industry as of 2018 and is expected to continue to grow37. Vaginal hygiene products include washes, wipes, moisturizers and creams, and other products. Researchers must be careful to use language that includes the diverse range of products people could be using, as asking about douching practices alone will not capture the full range of vaginal hygiene products known to impact the vaginal microbiome.
The use of vaginal cleansing products can have detrimental effects on vaginal health through several mechanisms. Soap is basic; the use of intravaginal vaginal cleansing products can disrupt the microbial community and prompt changes in the composition of the vaginal environment that can contribute to the development of disease38,39. Additionally, douching is capable of inhibiting the growth of Lactobacillus in vitro39and changing the vaginal microbiome of women undergoing STI treatment40. One study found that of 1435 participants in Canada, 95% reporting using at least one vaginal hygiene product. Participants who used any vaginal product had nearly three times higher odds of an adverse health condition such as reported history of BV, yeast infection, UTI, or STI41.

Diet

The human diet independent of probiotic consumption appears to impact the vaginal community. A study comparing the vaginal microbiomes of seven different primate species recently found that Lactobacillus dominated vaginal communities are a uniquely human phenomenon10. This is driven by the increased starch in human diets, which leads to increased glycogen deposition in the vaginal wall. As Lactobacillus breaks down glycogen for nutrients, the human vaginal environment became an excellent host for Lactobacilli species. It remains unclear if ɑ-amylase is always required for Lactobacillus to break down glycogen10,42, and what level of starch consumption must be maintained for Lactobacillus to be viable in the vagina.
Studies examined the impact of probiotics in the form of yogurt and capsulated freeze dried bacteria on vaginal symptoms. More thorough reviews are provided elsewhere43–45, though an overview is provided here. While oral probiotic administration has been found to have a beneficial effect on vaginal symptoms and some pregnancy outcomes46–48, a vaginally administered probiotic was found to have no clinical effect49. A clinical trial investigating the effects of probiotics on preterm birth found that, while the probiotic did not reduce incidence of preterm birth, it did shift the composition of the vaginal microbiome towards an environment that is associated with lower inflammation and pathogen abundance50. A prospective cohort study found that women who ate milk-based probiotics containing Lactobacillus had lower rates of preterm birth and preeclampsia51. Despite these findings, a recent meta analysis did not find an effect of probiotics on preterm birth48. Further research needs to determine the mechanisms at play and whether probiotics are truly beneficial for vaginal health.
There is also evidence that micronutrients impact the vaginal microbiome and vaginal health. Increased dietary fat is associated with increased risk for BV, while increased intake of folate, vitamin A, and calcium was associated with decreased risk for BV52. A study of the fecal microbiome of lactating women found that micronutrient intake was associated with the relative abundance of specific, individual taxa53. Only the relative abundance of the phylum Firmicutes increased as more nutrient rich food was consumed. This implies that any dietary interventions will need to tailor the intervention to the specific health condition or taxa that is targeted. Taken together, these findings may be especially important for understanding the dynamics of the vaginal microbiome for patients who don’t have access to or don’t consume nutrient rich food.

Sexual Partners and Practices

Sexual partners impact the vaginal microbiome as there is direct contact between genitals and transfer of microbiota and fluids. Individuals with more sexual partners are consistently found to have a more diverse vaginal microbiome17,18. This is thought to be due to exposure to many microbes, as each sexual partner can carry different microbes and the disturbance of the vaginal microbiome as a result of fluid exchange between partners (whether that be saliva, semen, or vaginal fluid). Having more female sexual partners is associated with higher risk for exposure to pathogenic microbes, as female partners are more likely to carry BVAB, Group B Streptococcus, and other microbes thought to be detrimental to vaginal health54. It is thought that increased vaginal microbiome diversity, whether from the number or sex of sexual partners, is overall negative for vaginal health. However, this primarily rises out of the concept that diversity is present in unhealthy vaginal communities when Lactobacillus is in low abundance or absent. It is unclear whether diversity alone is a risk factor for poor vaginal health.
Sexual practices also have been shown to impact the vaginal microbiome. Increased male condom use is found to be associated with decreased risk for BV, likely due to exposure prevention11,28,55. Similarly, male circumcision is associated with decreased risk of BV for female sexual partners. Unprotected receptive oral sex appears to be associated with increased risk for BV, though this finding is not always replicated56. The effects of lubricant on the vaginal microbiome remains significantly understudied, but a recent observational study found that lubricant use in the day prior to vaginal sampling was associated with a higher Nuget score57. Birth control method and vaginal sex after anal sex are also associated with changes in the microbiome3,55, those these changes are not clearly defined yet.

Gender Affirming Treatment

It is important for health care providers to be prepared to care for a diverse population of patients, and for health science researchers to contextualize their research to the care provided for different populations. This includes groups utilizing hormone therapies and other gender affirming treatments. Gender affirming treatments, such as masculinizing hormone therapy or neovaginal surgery, can impact the vaginal microbiome in clinically important ways. Masculinizing hormone therapy was found to increase the diversity of the vaginal microbiome, and individuals undergoing this treatment were more likely to fall into the Diverse CST58. Longitudinal sampling will be required to identify whether masculinizing hormone therapy changes one’s CST or if the baseline CST is the diverse group.
One gender affirming therapy for transgender women is neovaginal surgery, in which a vagina is constructed from existing penile and scrotal tissue and/or a colon graft. While research on the vaginal microbiome of those who undergo neovaginal surgery has been limited, new research indicates that understanding the neovaginal microbiome is clinically important. One study found that the neovaginal microbiome was highly diverse, composed largely of anaerobic bacteria, and triggered a host response similar to the response to BV59. Another study examining the neovaginal microbiome of five women with candida infection following neovaginal surgery found these women also had more BVAB in their vaginal microbiome60. Importantly, all five women in this study experienced several negative vaginal symptoms that were attributed to the microbiome and not just candida infection. In both studies, it was found that their vaginal microbiome was more similar to the skin and gut microbiome, possibly due to skin grafts during neovaginal surgery. There is high therapeutic potential in understanding how the vaginal microbiome contributes to symptoms following neovaginal surgery, but it is a multifaceted problem with many important considerations reviewed extensively in Mundluru & Larson, 201861.

Stress

Stress can capture many different experiences, from physical stress to psychosocial stress. Several mechanisms of stress-induced vaginal community disruption have been identified. First, stress-induced cortisol can bind to glucocorticoid receptors in the vaginal wall, which leads to an increase in proinflammatory cytokines, chemokines, and cause immunosuppression62. Further, stress-induced cortisol can inhibit the deposition of glycogen in the vaginal lining in a manner which restricts the Lactobacilli population63. It is possible that people who experience higher levels of stress have a vaginal microbiome that has adapted to rely on anaerobes which create an acidic environment without solely relying on Lactobacillus. Healthy Black and Hispanic individuals, who are less likely to harbor Lactobacillus in their vaginal microbiome, are more likely to experience high levels of stress and more likely than those of other ethnicities to have anaerobes in their vaginal community 5,69. Taken together, this indicates that the vaginal microbiome adapts to not rely on Lactobacillus in the face of stress, as stress makes the vaginal environment less hospitable to Lactobacillus.

Broader Social Determinants

Social determinants of health refer to the social and economic context in which someone is born and lives that influence their health64. This can manifest as access to affordable healthcare and housing, experiences of discrimination, and structural oppression65. Groups who experience greater disease burden tend to be impacted by social determinants of health. While there has not been research that has specifically examined how social determinants impact the vaginal microbiome, there has been work that indicates access to care and other social determinants impact the microbiome in a clinically relevant way66. A further review of the microbiome through the lens of social equity is available67and is important for thinking about how structural barriers impact the health of one’s microbiome. It is plausible that physiologic adaptations and changes in the microbiome may be driven by larger societal and systemic stressors such as racism, poverty, and education which influence health behaviors, decisions, and choices.