Vaginal epithelial dysfunction is mediated by the microbiome, metabolome, and mTOR signaling - Participant Group 2
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ABSTRACT: Bacterial vaginosis (BV) is characterized by depletion of Lactobacillus and overgrowth of anaerobic and facultative bacteria, leading to increased mucosal inflammation, epithelial disruption, and poor reproductive health outcomes. However, the molecular mediators contributing to vaginal epithelial dysfunction are poorly understood. Here we utilized proteomic, transcriptomic and metabolomic analyses to characterize biological features underlying BV in 405 African women and explored functional mechanisms using bacterial co-cultures in vitro. We identified five major vaginal microbiome groups, (L.crispatus(21%), L.iners(18%), any non-specific Lactobacillus species(9%), Gardnerella species .vaginalis(30%), or polymicrobial(22%)). Using multi-‘omics we show that BV associated epithelial disruption and mucosal inflammation are linked to the mammalian target of rapamycin (mTOR) pathway and associate with Gardnerella.vaginalis, Mobiluncus mulieris, and specific metabolites including imidazole propionate. Bacterial co-culture experiments in vitro confirmed that type strain G.vaginalis and, M.mulieris supernatants as well as imidazole propionate, directly affect epithelial barrier function and are accompanied by activation of mTOR pathways. These results establish the microbiome-mTOR axis as a central feature of epithelial dysfunction in BV.
INSTRUMENT(S): LTQ Orbitrap Velos
ORGANISM(S): Homo Sapiens (human)
TISSUE(S): Cervicovaginal Fluid
SUBMITTER: Kenzie Birse
LAB HEAD: Adam Burgener
PROVIDER: PXD040280 | Pride | 2023-07-20
REPOSITORIES: Pride
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