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19: Distinct microbiota from the cervicovaginal space compromise the cervical epithelial barrier and alter expression of microRNAs

      Objective

      Emerging data suggests that certain cervicovaginal (CV) microbiota are associated with an increased risk of spontaneous preterm birth (sPTB), although the mechanism remains unclear. We have previously shown a specific microRNA (miRNA) profile in the CV space of women months prior to having sPTB and that these specific miRNAs disrupt the cervical epithelial barrier. Therefore, we hypothesize that microbial byproducts may alter the miRNA profile of cervical cells, thereby contributing to epithelial barrier dysfunction and cervical remodeling.

      Study Design

      Human ectocervical cells (Ectos) were treated for 48 hours with bacterial supernatants isolated from cultures of Mobiluncus mulieris (n=3), Gardnerella vaginalis (n=3) and Lactobacillus crispatus (n=3). Ectos treated with bacterial growth media alone, as well as non-treated cells, were used as controls. Epithelial permeability assays were performed using bacterial supernatant from M. mulieris. From all 3 bacterial exposures, RNA was also isolated and miRNA expression was measured by QPCR. miRNAs were chosen if they had a known association with either sPTB or a shorter gestational length. For select miRNAs, confirmed downstream targets relevant to cervical barrier function were investigated.

      Results

      M. mulieris supernatant significantly compromised Ecto permeability when compared to non-treated controls (Figure 1, p=3). Treatment with the supernatants from L. crispatus, G. vaginalis, and M. mulieris resulted in increased expression of select but different miRNAs (Table 1). Treatment with M. mulieris supernatant did not alter the expression of any of the predicted downstream targets.

      Conclusion

      Select CV bacterial byproducts have the ability to compromise the cervical epithelial barrier and induce epigenetic changes. Bacteria associated with an unhealthy vaginal state, M. mulieris and G. vaginalis, induced breakdown of the cervical epithelial barrier and an up-regulation of specific miRNAs. The ability of these two bacteria, but not L. crispatus, to induce differential miRNA expression suggest that these bacteria are having diverse functional effects on cervical epithelial cells, though further research is needed to determine the mechanisms by which these CV bacteria promote cervical remodeling.
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