# Breast Milk IgA Exerts Selective Pressure on the Preterm Gut Microbiome

> **NIH NIH F30** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2024 · $52,694

## Abstract

PROJECT SUMMARY
 This proposal aims to characterize how breast milk IgA shapes the ecological development of the preterm
gut microbiome and promotes resistance to pathobionts. Aberrant gut bacterial colonization places the preterm
infant at risk for necrotizing enterocolitis (NEC). NEC is a deadly inflammatory intestinal disease that uniquely
affects preterm infants and lacks curative treatments. Our laboratory has found that protection against NEC is
associated with preterm gut microbiota that are bound by maternal milk-derived IgA (mIgA). Enterobacteriaceae
that do not bind to mIgA predominate the gut microbiome of preterm infants who develop NEC. In contrast,
infants who do not develop NEC establish a mature or ‘term-like’ microbiome comprising obligate anaerobes.
We reasoned reduced mIgA binding to Enterobacteriaceae prior to NEC development is due to either: 1) variation
in the mIgA repertoire over time in breast milk, or 2) genetic changes that enable specific bacterial strains to
evade mIgA recognition. Interestingly, our preliminary data show that anti-bacterial mIgA reactivity remains stable
over time within an individual mother. Thus, our central hypothesis is that Enterobacteriaceae escape from
mIgA binding delays the maturation of the preterm infant gut microbiome.
 Understanding how the preterm gut microbial ecosystem resists Enterobacteriaceae colonization first
requires defining how the microbiome forms, matures, and functions. To address this gap in knowledge, we will
utilize novel technology developed by our laboratory that combines RNA hybridization chain reaction, flow
cytometry, and direct quantitative analyses to determine whether mIgA binds to Enterobacteriaceae to restrict
their colonization (Aim 1.1) and how mIgA promotes the establishment of obligate anaerobes (Aim 1.2) in
longitudinally collected preterm infant stool from a prospective cohort study. In doing so, we may be able to
identify signature patterns of microbiota development that differentiates patients by NEC status. To delineate the
genetic mechanisms underlying how Enterobacteriaceae lose mIgA binding and potentially induce NEC, we will
perform single cell microbial sequencing that incorporates anti-IgA barcoding, allowing us to link changes in
genetic features with or without IgA binding to distinct strains (Aim 2). This novel approach will enable us to study
ex vivo bacterial evolution as a response to mIgA binding in preterm infant stool, which has significant
translational value for preterm infants with microbiome-related disease. By defining genes involved in bacterial
evasion of antibody binding, this work may open new avenues for targeted therapy against NEC.
 This project provides a unique opportunity for me to: 1) gain computational expertise to analyze large
genomic and patient-centered datasets, and 2) form clinical and research collaborations tailored to my career
goal of becoming an OB/GYN physician scientist. The proposed research will enable me ...

## Key facts

- **NIH application ID:** 10823919
- **Project number:** 1F30HD114316-01
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Christine Melody Tin
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $52,694
- **Award type:** 1
- **Project period:** 2024-01-01 → 2028-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10823919

## Citation

> US National Institutes of Health, RePORTER application 10823919, Breast Milk IgA Exerts Selective Pressure on the Preterm Gut Microbiome (1F30HD114316-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10823919. Licensed CC0.

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