Early Vaginal Microbiome Research

The vaginal microbiome is simpler than the microbiome of other body sites―a few species tend to dominate the vaginal microbiome, and all vaginal microbiomes can be categorized by a few enterotypes, or community profile. As such, there is a relatively uniform framework for characterizing the vaginal microbial community. Community state types (CSTs) were originally introduced in 2011 as a way of categorizing the composition of the vaginal microbiome5. The prevailing literature finds that there are five principal CSTs―four are marked by the dominance of Lactobacillus species and one is marked by the absence of this dominant member. This fifth CST, dubbed the “Diverse CST,” consists of a lower prevalence ofLactobacillus along with a greater prevalence and number of other anaerobic microbes. The original analysis introducing CSTs noted that healthy women of different races and ethnicities exhibited different proportions of the five CSTs, but that, importantly, all CSTs were common in healthy women across all racial and ethnic groups.
Later literature further simplified characterization of the vaginal microbiome into a narrower concept - Lactobacillus dominated communities versus diverse ones7. The presence of Lactobacillus tends to correlate with lower rates of sexually transmitted infections (STI)3, lower rates of pregnancy complications8, and lower diagnosed cases of Bacterial Vaginosis (BV)9. The plausible biological mechanism by which Lactobacillus exerts its protective effect is through the digestion of glycogen in the vaginal lining into lactic acid, creating a highly acidic vaginal environment. This acidic environment is hostile to the growth and proliferation of many pathogens that cause STIs and BV associated bacteria (BVAB). The proposed mechanism is difficult to experimentally test as even closely related animal models are physiologically different from humans10, and it can be unethical to experimentally test this in humans. As such, studies on the human vaginal microbiome are almost entirely observational.
Observational studies of the human microbiome often fail to account for many clinical and lifestyle factors, such as comorbid conditions, birth control method11, and recent sexual contact12, that have the potential to moderate the relationships observed between the vaginal microbiome and reproductive health risks. For example, it is largely unknown how comorbid conditions impact the vaginal microbiome despite their impact on the gut microbiome being known13–16. Further, sexual practices, most recent sexual contact, and birth control are not always accounted for despite being known to impact the vaginal microbiome3,11,17,18. When CSTs were introduced, it was noted that Black and Hispanic women were more likely than women of other ethnicities to fall into the Diverse CST5. The women in this study were healthy with no reported vaginal symptoms. As such, the authors cautioned against assuming that the absence ofLactobacillus indicated an unhealthy state.