Towards a deeper understanding of the vaginal microbiota

Abstract

The human vaginal microbiota is a critical determinant of vaginal health. These communities live in close association with the vaginal epithelium and rely on host tissues for resources. Although often dominated by lactobacilli, the vaginal microbiota is also frequently composed of a collection of facultative and obligate anaerobes. The prevalence of these communities with a paucity of Lactobacillus species varies among women, and epidemiological studies have associated them with an increased risk of adverse health outcomes. The mechanisms that drive these associations have yet to be described in detail, with few studies establishing causative relationships. Here, we review our current understanding of the vaginal microbiota and its connection with host health. We centre our discussion around the biology of the vaginal microbiota when Lactobacillus species are dominant versus when they are not, including host factors that are implicated in shaping these microbial communities and the resulting adverse health outcomes. We discuss current approaches to modulate the vaginal microbiota, including probiotics and vaginal microbiome transplants, and argue that new model systems of the cervicovaginal environment that incorporate the vaginal microbiota are needed to progress from association to mechanism and this will prove invaluable for future research.

Fig. 1 |. Effect of the menstrual cycle on the vaginal microenvironment.

During the menstrual phase (M; red), blood and the shed functional layer of the uterine endometrium flow through the vagina. During the subsequent proliferative phase (P; blue), higher estrodiol levels promote the growth and maturation of the vaginal epithelium. The mucus is thinner during this stage, which is thought to facilitate sperm penetration. Following ovulation (O; orange), progestrerone levels rise during the secretory phase (L; green), halting growth and maturation of the epithelium. Superficial cells of the epithelium are shed and the protective mucus layer is thicker.

Fig. 2 |. The biology of Lactobacillus crispatus in the vaginal microbiota.

When lactobacilli (red) dominate the vaginal microbiota, less beneficial bacteria (blue) are lower in abundance. Lactobacillus spp. produce PulA, a glycogen-degrading enzyme that generates smaller glucose polymers that are then imported into the cell and fermented via pyruvate (Pyr), producing lactic acid isomers (D-La and L-La). This acidifies the microenvironment to a pH <4. Glycogen breakdown products can also be used to produce hydrogen peroxide (H₂O₂). Growth of less beneficial bacteria is suppressed by the low vaginal pH and bacterial products, such as lactic acid, bacteriocins and H₂O₂. D-lactic acid production and S-layer proteins can modulate host immune function in an anti-inflammatory manner.

Fig. 3 |. The CST IV vaginal microbiota.

a, The CST IV vaginal microbiota is comprised of a more even collection of Gardnerella (Blue), Prevotella (Green, Yellow), Atopobium (Purple), Ca. L. vaginae (Brown, flagellated) and is associated with a higher pH (>4.5). These bacteria produce biogenic amines that raise vaginal pH, impact host physiology, and inhibit the growth of Lactobacillus. These species can break down glycogen produced by the host to produce acetate (Ac), for example, using sialidase and fucosidase enzymes. Production of cytolysin enzymes by Gardnerella and other species allow the community to liberate more resources through the lysis of host cells. b, A subset of CST IV communities has the potential to degrade host mucin glycochains due to their ability to produce sialidase and fucosidase enzymes. If the mucus layer is degraded faster than it can be replenished, the integrity of the protective mucus layer might become compromised, exposing the vaginal epithelium to further damaged by cytolytic activity.

Fig. 4 |. Vaginal microbiota interventions to treat bacterial vaginosis.

Existing treatments include antibiotics such as metronidazole, estrogen therapy, lactic and boric acid, and vaginal lactobacilli probiotics. However, these interventions vary in their success and do not effectively prevent recurrent/recalcitrant BV. Vaginal microbiota transplants (VMTs) are a promising intervention for BV. A suitable donor with a Lactobacillus dominant vaginal microbiota is identified. Vaginal secretions are collected from the donor, screened for various STIs, and processed. The processed vaginal secretions are then introduced into the vagina of a recipient who is typically experiencing recurrent/recalcitrant BV. The recipient may or may not be treated with antibiotics prior to the transplant. Success is defined as a long-lasting resolution of the recipient’s BV and a shift of their vaginal microbiota to the Lactobacillus dominant configuration.