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

TL;DR

This study shows how different vaginal microbes affect the genetic and epigenetic activity of cervical and vaginal cells, influencing reproductive health outcomes.

Contribution

The study reveals specific molecular pathways altered by Gardnerella vaginalis and Lactobacillus crispatus in cervical epithelial cells.

Findings

Gardnerella vaginalis activates inflammasome pathways and increases caspase-1 and IL-1β in epithelial cells.

Lactobacillus crispatus supernatants reduce chromatin accessibility in cervical epithelial cells.

Host-microbe interactions in the reproductive tract may offer therapeutic strategies for improving reproductive health.

Abstract

The cervicovaginal microbiome is highly associated with women’s health, with microbial communities dominated by Lactobacillus species considered optimal. Conversely, a lack of lactobacilli and a high abundance of strict and facultative anaerobes, including Gardnerella vaginalis, 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 in vitro cervicovaginal epithelial transcriptional response to different vaginal bacteria and their culture supernatants. We showed that G. vaginalis upregulates genes associated with an activated innate immune response. Unexpectedly, G. vaginalis specifically induced inflammasome pathways through activation of NLRP3-mediated increases in caspase-1, IL-1β and cell death, while live L. crispatus had minimal transcriptomic changes on epithelial cells. L. crispatus 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.

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