Vaginal bacteria-derived extracellular vesicles diffuse through human cervicovaginal mucus to enable microbe-host signaling.

The composition of the vaginal microenvironment has significant implications for gynecologic and obstetric outcomes. Where a Lactobacillus-dominated microenvironment is considered optimal, a polymicrobial environment is associated with increased risk for female reproductive diseases. Recent work examined bacteria-derived extracellular vesicles (bEVs) as an important mode of microbe-host communication that may influence reproductive outcomes. However, in order to communicate with female reproductive tissues, bEVs must penetrate the protective cervicovaginal mucus barrier. We demonstrate increased diffusion of bEVs compared to whole bacteria. Additionally, we evaluate the uptake of bEVs by, and the resulting effects on, human vaginal epithelial, endometrial, and placental cells, highlighting potential mechanisms of action by which vaginal dysbiosis contributes to gynecologic and obstetric diseases. Taken together, our work demonstrates the ability of bEVs to mediate female reproductive outcomes and highlights their potential as therapeutic modalities for treating dysbiosis and dysbiosis-associated diseases in the female reproductive tract.