LPS-induced endometrial cell-derived exosomes suppress probiotic Lactobacillus growth

Spontaneous preterm birth (sPTB) has been increasingly associated with alterations in vaginal microbiota. While Lactobacillus spp., which physiologically dominate the cervical microbiota, are considered protective with a lower risk of intra-amniotic infection and chorioamnionitis, other microbes such as Gardnerella vaginalis are associated with an increased risk of sPTB. Although this association is well documented, the host mechanisms that regulate the composition of vaginal microbial communities remain poorly understood. Emerging evidence suggests that host-derived exosomes may play a critical role in shaping the microbial environment. This study hypothesized that endothelial cell-derived exosomes may modulate the growth of probiotic Lactobacillus spp. through changes in microRNA cargo, thereby influencing the risk of sPTB. To investigate this hypothesis, HEC-1-A cells were stimulated with lipopolysaccharides (LPS), and exosomes were isolated from these cells. These exosomes were then applied to four Lactobacillus strains (L. crispatus, L. gasseri, L. jensenii, L. reuteri) to evaluate how LPS-induced alterations in exosomal microRNA content affect probiotic growth. The results indicate that exosomes derived from LPS-stimulated HEC-1-A cells inhibited the four bacterial strains and facilitated the expansion of the opportunistic pathogen G. vaginalis in a mixed-culture system. MicroRNA sequencing revealed that LPS stimulation increased the levels of miR-181d-5p and miR-181c in these exosomes, both of which may contribute to the suppression of Lactobacillus spp. growth. Taken together, these findings suggest a novel regulatory pathway in which host-derived exosomes influence the vaginal microbiota, suggesting that disruptions in this mechanism may contribute to vaginal dysbiosis and increase the risk of sPTB.