Vaginal microbes alter epithelial transcriptome and induce epigenomic modifications providing insight into mechanisms for susceptibility to adverse reproductive outcomes.

The cervicovaginal microbiome is highly associated with women's health, with microbial communities dominated by species considered optimal. Conversely, a lack of lactobacilli and a high abundance of strict and facultative anaerobes, including , have been associated with adverse reproductive outcomes. However, how host-microbial interactions alter specific molecular pathways and impact cervical and vaginal epithelial function remains unclear. Using RNA-sequencing, we characterized the cervicovaginal epithelial transcriptional response to different vaginal bacteria and their culture supernatants. We showed that upregulates genes associated with an activated innate immune response. Unexpectedly, specifically induced inflammasome pathways through activation of NLRP3-mediated increases in caspase-1, IL-1β and cell death, while live had minimal transcriptomic changes on epithelial cells. culture supernatants resulted in a shift in the epigenomic landscape of cervical epithelial cells that was confirmed by ATAC-sequencing showing reduced chromatin accessibility. This study reveals new insights into host-microbe interactions in the lower reproductive tract and suggests potential therapeutic strategies leveraging the vaginal microbiome to improve reproductive health.