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Record W4372403945 · doi:10.1016/j.celrep.2023.112474

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

2023· article· en· W4372403945 on OpenAlexafffund
Alicia R. Berard, Douglas K. Brubaker, Kenzie Birse, Alana Lamont, Romel D. Mackelprang, Laura Noël‐Romas, Michelle Perner, Xuanlin Hou, Elizabeth Irungu, Nelly Mugo, Samantha Knodel, Timothy R. Muwonge, Elly Katabira, Sean M. Hughes, Claire Levy, Douglas A. Lauffenburger, Jared M. Baeten, Connie Celum, Florian Hladik, Jairam R. Lingappa, Adam Burgener

Bibliographic record

VenueCell Reports · 2023
Typearticle
Languageen
FieldImmunology and Microbiology
TopicReproductive tract infections research
Canadian institutionsUniversity of Manitoba
FundersInstitute for Collaborative BiotechnologiesArmy Research OfficeBill and Melinda Gates FoundationNational Institute of Allergy and Infectious DiseasesCanadian Institutes of Health ResearchNational Institutes of HealthGilead Sciences
KeywordsMetabolomeBiologyBacterial vaginosisLactobacillus crispatusPI3K/AKT/mTOR pathwayMicrobiomeTranscriptomeMicrobiologyLactobacillusGardnerella vaginalisMetabolomicsSignal transductionCell biologyBioinformaticsBacteriaGeneticsGene expressionGene

Abstract

fetched live from OpenAlex

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 mechanisms in vitro. We identify five major vaginal microbiome groups: L. crispatus (21%), L. iners (18%), Lactobacillus (9%), Gardnerella (30%), and polymicrobial (22%). Using multi-omics we show that BV-associated epithelial disruption and mucosal inflammation link to the mammalian target of rapamycin (mTOR) pathway and associate with Gardnerella, M. mulieris, and specific metabolites including imidazole propionate. Experiments in vitro confirm that type strain G. vaginalis and M. mulieris supernatants and imidazole propionate directly affect epithelial barrier function and activation of mTOR pathways. These results find that the microbiome-mTOR axis is a central feature of epithelial dysfunction in BV.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesInsufficient payload (model declined to judge)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.231
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.001

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.014
GPT teacher head0.256
Teacher spread0.241 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations56
Published2023
Admission routes2
Has abstractyes

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