Dataset Information

Vaginal epithelial dysfunction is mediated by the microbiome, metabolome, and mTOR signaling - Participant Group 2

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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			Action	DRS
	03796-1-003_Mix_1_Endo_V-01.raw	Raw
	03796-1-006_530121293644_V.raw	Raw
	03796-1-007_540160023644_V.raw	Raw
	03796-1-009_530123783644_V.raw	Raw
	03796-1-011_530103413644_V.raw	Raw

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Vaginal epithelial dysfunction is mediated by the microbiome, metabolome, and mTOR signaling.

Berard Alicia R AR Brubaker Douglas K DK Birse Kenzie K Lamont Alana A Mackelprang Romel D RD Noël-Romas Laura L Perner Michelle M Hou Xuanlin X Irungu Elizabeth E Mugo Nelly N Knodel Samantha S Muwonge Timothy R TR Katabira Elly E Hughes Sean M SM Levy Claire C Calienes Fernanda L FL Lauffenburger Douglas A DA Baeten Jared M JM Celum Connie C Hladik Florian F Lingappa Jairam J Burgener Adam D AD

Cell reports 20230506 5

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 utilize proteomic, transcriptomic, and metabolomic analyses to characterize biological features underlying BV in 405 African women and explore functional mech ...[more]

PMID: 37149863

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