# Evaluating the impact of human milk oligosaccharides on the vaginal microenvironment

> **NIH NIH R21** · BAYLOR COLLEGE OF MEDICINE · 2024 · $234,670

## Abstract

Project Summary
Formation and maturation of the human microbiota is associated with lifelong health outcomes, and its initial
composition is heavily influenced by the maternal vaginal microbiota. Perturbations to the maternal vaginal
microbiota in pregnancy or intrapartum are associated with increased risk of multiple health disorders from
preterm birth to developing immune or metabolic disease later in life. Factors that promote an optimal transfer of
microbes to the infant are undefined, and to date, knowledge of this critical process is largely descriptive or
correlative. We seek to overcome this barrier by applying recent advances in model development, particularly
the use of gnotobiotic animals, three-dimensional tissue culture, and cultivation of complex microbial
communities, to generate experimental evidence for host and microbial factors shaping the maternal vaginal
environment during pregnancy. With these models in hand, we will test a hypothesis proposing an entirely novel
mechanism of maternal influence on the initial infant microbiota. Breastfeeding is consistently associated with
improved infant health, reduced risk of infectious disease, and accelerated immune and microbial maturation
within the gut. Human milk oligosaccharides (HMOs), the third most abundant component of breastmilk, serve
as prebiotics for the developing microbiota and shape immune development and tolerance at the gut epithelium.
Quite recently, it has become apparent that HMOs are systemically present during pregnancy, suggesting a
wider influence on maternal and fetal biology than previously appreciated. Clinical studies have correlated
maternal serum HMOs with vaginal microbiome signatures and genetic variants in HMO production are linked
with vaginal pathogen colonization and risk for preterm birth. The central hypothesis of this proposal is that HMOs
modulate the maternal vaginal microenvironment in pregnancy to promote growth of beneficial microbes for
seeding the infant gut and to concurrently support barrier function and limit maternal inflammation. We will test
this hypothesis by: 1) Characterizing the biological activity of HMOs towards human vaginal communities in vitro
and in humanized gnotobiotic mice, and 2) Evaluating immunomodulatory impacts of HMOs at the vaginal
mucosa using human vaginal organoids and gnotobiotic and germ-free mouse models. This research approach
is a complementary merger of the applicant’s background in microbial pathogenesis and animal models of
vaginal colonization and host-microbiome interactions, and the institutional strengths of BCM in the areas of
human microbiome clinical research, human organoid development, and microbiome innovation and
therapeutics. This high impact project will apprise the basic biology of HMO activity in the vaginal tract and
provide a therapeutic tactic to better harness the potential of HMOs in modulating vaginal microbes and immunity.
The breadth of experience necessary to complete this project ...

## Key facts

- **NIH application ID:** 10815787
- **Project number:** 5R21HD111910-02
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Katy Patras
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $234,670
- **Award type:** 5
- **Project period:** 2023-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10815787

## Citation

> US National Institutes of Health, RePORTER application 10815787, Evaluating the impact of human milk oligosaccharides on the vaginal microenvironment (5R21HD111910-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10815787. Licensed CC0.

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