# Unraveling mechanisms by which cervicovaginal microbiota can promote or prevent cervical remodeling and preterm birth

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2021 · $655,818

## Abstract

Summary: Every year, 15 million babies are born premature. Over 75% of preterm births (PTBs) are termed
spontaneous (sPTB) resulting in parturition at early gestational time points without clear causes. Our lack of
understanding of the mechanisms and overall pathogenesis that promotes sPTB results in limited successful
interventions. While uterine contractility and cervical remodeling appear to be obligatory processes in
parturition, premature triggers of these processes remain poorly elucidated. Recent studies reveal close
associations between cervicovaginal (CV) microbial communities and the occurrence of sPTB. In particular, we
recently studied a cohort of 2000 pregnant women and assessed the CV microbial communities, metabolic and
immune responses early in pregnancy, providing strong evidence that colonization with specific bacterial taxa,
specific metabolic profiles, and local immune responses were strongly associated with sPTB. However, to
develop preventive or therapeutic strategies, understanding the cause of sPTB is essential. We speculate that
interplay between the CV microbial communities, local immune response and the cervical and vaginal epithelial
barriers induce premature cervical remodeling and initiate sPTB. The overall goal of this study is to define
how specific CV bacteria interact with vaginal and epithelial cells in clinically relevant in vitro and in vivo
models and to understand how those interactions modify tissue remodeling and biomechanics of the pregnant
cervix, driving sPTB. We propose a process whereby bacterial taxa that are highly associated with sPTB in
humans provoke exfoliation of the vaginal epithelium. This process promotes epithelial-mesenchymal transition
(EMT) from both vaginal and cervical epithelial cells. While activation of EMT prevents the ascension of these
bacteria, a tradeoff is that EMT fosters breakdown of the extracellular matrix in the cervical tissue, triggering
premature cervical remodeling and sPTB. Therefore, our central hypothesis is that specific bacteria, such as
Gardnerella vaginalis (G.vaginalis), promote EMT of the vaginal and cervical epithelial barrier which alters the
structure and function of the pregnant cervix, leading to sPTB, even in the absence of ascending infection
(above the cervix). This paradigm-shifting hypothesis will be tested through a series of in vitro and in vivo
experiments. This proposal will first address whether ascension of bacteria into the uterus is actually necessary
for PTB to occur; these studies have the potential to reframe our scientific and therapeutic approach to PTB.
We will then demonstrate how bacteria induce EMT in CV epithelial barriers and how EMT might promote
premature cervical remodeling. Unique to this proposal, we will provide quantitative assessment of the
pregnant cervix, in terms of structure and function, in a mouse model of PTB. A multidisciplinary team adds
rigor to our work by applying novel concepts and techniques to the study of s...

## Key facts

- **NIH application ID:** 10223393
- **Project number:** 5R01HD098867-02
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** MICHAL Aviva ELOVITZ
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $655,818
- **Award type:** 5
- **Project period:** 2020-08-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10223393

## Citation

> US National Institutes of Health, RePORTER application 10223393, Unraveling mechanisms by which cervicovaginal microbiota can promote or prevent cervical remodeling and preterm birth (5R01HD098867-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10223393. Licensed CC0.

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