# A large scale investigation of the vaginal metagenome and metabolome and their role in spontaneous preterm birth

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2024 · $674,872

## Abstract

ABSTRACT
Spontaneous preterm birth (sPTB) is a leading cause of neonatal morbidity and mortality. Despite extensive
research and medical efforts, we lack both the means to identify it early and the therapeutic options to prevent it
when identified. The vaginal microbiome is believed to have a causal role in a substantial fraction of sPTBs, and
multiple studies have shown that even when measured early in pregnancy, the microbiome is associated with
adverse pregnancy outcomes. Despite this great promise, robust microbiome-based predictors for sPTB have
not been developed yet, and we lack a detailed understanding of the mechanisms underlying its involvement in
sPTB. We attribute this to a small sample size in current studies; the aggregative definition of sPTB as a binary
variable, ignoring its heterogeneous presentations and etiologies; and a focus on microbial taxonomy instead of
data that is more functionally and mechanistically oriented. We propose to capitalize on one of the largest and
best-phenotyped pregnancy cohorts collected to date, the nuMoM2b study. This was a national, multi-center trial
that collected vaginal swabs at three time-points from women with diverse geographic and demographic
backgrounds. This study profiled nearly 500 women with sPTB, almost an order of magnitude more than any
previous microbiome study. We have compiled an interdisciplinary team with intimate knowledge of the
nuMoM2b study, ample experience in compiling, profiling, and analyzing large-scale microbiome and
metabolomic cohorts, and a track record of innovation in microbiome analysis and its clinical applications. We
will perform deep metagenomic sequencing, longitudinal sample sequencing, and matched metabolomic
analysis of a total of almost 6,000 samples from nearly 1,500 pregnant women, generating the largest such
dataset to date. This dataset would advance the microbiome community, drive discovery in the field, and enable
us and other researchers to study host-microbiome interactions, in general and specifically in the context of
sPTB, with an unprecedented depth. Our proposed data analysis offers a nuanced and high-resolution view of
both clinical and biological data. We will study sPTB while accounting for its various clinical presentations,
etiologies, and important maternal covariates. We will study the vaginal ecosystem from multiple angles,
investigating microbial genomic adaptations, levels of metabolites in the ecosystem, and dynamic changes to
the microbiome profile. We will devise an aggregative computational framework, based on state-of-the-art
methods and algorithms, that provides early prediction of sPTB based on microbiome-related features. We will
employ a combination of parametric and non-parametric methods to obtain mechanistic insights into host-
microbiome interactions that potentially contribute to sPTB and other adverse pregnancy outcomes. Altogether,
this study will be transformative to our understanding of the vaginal microbiome in a...

## Key facts

- **NIH application ID:** 10892059
- **Project number:** 5R01HD106017-04
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Tal Korem
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $674,872
- **Award type:** 5
- **Project period:** 2021-08-03 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10892059

## Citation

> US National Institutes of Health, RePORTER application 10892059, A large scale investigation of the vaginal metagenome and metabolome and their role in spontaneous preterm birth (5R01HD106017-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10892059. Licensed CC0.

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