Roles of the Microbiota of the Female Reproductive Tract in Gynecological and Reproductive Health

Abstract

The microbiome of the female reproductive tract defies the convention that high biodiversity is a hallmark of an optimal ecosystem. Although not universally true, a homogeneous vaginal microbiome composed of species of Lactobacillus is generally associated with health, whereas vaginal microbiomes consisting of other taxa are generally associated with dysbiosis and a higher risk of disease. The past decade has seen a rapid advancement in our understanding of these unique biosystems. Of particular interest, substantial effort has been devoted to deciphering how members of the microbiome of the female reproductive tract impact pregnancy, with a focus on adverse outcomes, including but not limited to preterm birth. Herein, we review recent research efforts that are revealing the mechanisms by which these microorganisms of the female reproductive tract influence gynecologic and reproductive health of the female reproductive tract.

Keywords: Lactobacillus; bacterial vaginosis; cervical microbiome; female reproductive tract; pregnancy; preterm birth; upper genital tract; uterine microbiome; vaginal microbiome; vaginitis.

FIG 1

Microbiome of the female reproductive tract. In the pie chart showing the composition of the VMB, the taxa are color coded and assigned to the species level. Species belonging to the genus Lactobacillus are highlighted by the gray stripe at the periphery of the pie chart. Data in the pie chart are from a previous study of 2,582 asymptomatic reproductive-age women, 27.2% of whom were pregnant and who had a racial distribution of 52% Black, 20% white, and 28% non-Black Hispanic (8). The VMB can be classified to five community state types (CSTs), and the predominant species in these CSTs are listed. The composition of the cervical microbiome is similar to that of the VMB. The existence of a microbiome in the upper female reproductive tract is still controversial.

FIG 2

Role of the vaginal microbiome in gynecologic and obstetric health. Maternal estrogen promotes the production of glycogen in vaginal epithelial cells. Glycogen released into the female reproductive tract by detachment from or lysing epithelial cells is metabolized to glucose and maltose by human and bacterial α-amylases. Glucose and maltose can be further fermented to lactic acid by Lactobacillus, consequently supporting proliferation of members of this genus. Lactic acid decreases the vaginal pH and, as a result, inhibits the colonization and proliferation of dysbiosis-associated species. Bacteriocins may play roles in controlling colonization and proliferation of microbes generally linked to BV and other adverse conditions. However, lactic acid seems to inhibit host inflammation potentially induced by infections with opportunistic microbes by increasing the anti-inflammatory cytokine IL-1RA and inhibiting proinflammatory cytokines and chemokines, including IL-6, IL-8, TNF-α, RANTES, and MIP-3α. Furthermore, Lactobacillus taxa also seem to promote the integrity of the mucosal and epithelial barriers, thus helping to prevent establishment of these deleterious microbes. In contrast, less favorable taxa induce adverse outcomes by inducing inflammation (circle 1), undergoing biofilm formation (circle 2), and producing other virulence factors, including but not limited to toxins (e.g., vaginolysin and inerolysin), proteases, mucinases, or sialidases (circle 3). See Table 2 for additional BV-associated virulence factors.

FIG 3

Shift of the vaginal microbiome in pregnancy. Estrogen is one of the key factors that modulate the stability of the VMB. The concentration of estrogen and the stability of the VMB increase during pregnancy. The abundance of lactobacilli increases at the expense of species often related to vaginal dysbiosis, e.g., G. vaginalis, A. vaginae, and P. bivia. This shift in the VMB occurs early in pregnancy and is more pronounced in Black women. After delivery, estrogen levels, along with the stability of the VMB, decrease greatly, and the VMB converts from an optimal state to a state of dysbiosis, which often takes over 40 weeks to recover.