# Defining bioactivities of peptides released from human milk proteins in the preterm infant intestine

> **NIH NIH R01** · OREGON HEALTH & SCIENCE UNIVERSITY · 2024 · $645,659

## Abstract

PROJECT SUMMARY
 Human milk, whether maternal or pasteurized donor human milk, is considered the ideal nutrition for
preterm infants. In addition to serving as a source of amino acids to support infant growth, human milk proteins
encode cryptic bioactive peptides released during infant digestion. These peptides can be found in the infant
intestine luminal fluid and have an array of biological activities, including antimicrobial, bifidogenic,
immunomodulatory, and effects on intestinal physiology. Although
peptides
responsible
peptides
 our initial work demonstrates that milk
released and present in the infant intestine have beneficial activities, identifying the specific peptides
for these gut-related actions has been limited. Thus, there is a critical need to determine the specific
released within the infant's gastrointestinal tract that mediate these bioactivities.
Our long-term goal is to leverage the biology of human milk to promote optimal development and growth
of preterm infants ex utero. The overall objective of this proposal is to demonstrate the presence and identities
of gut health-promoting human milk protein-derived peptides within the preterm infant intestine. Our central
hypothesis is that bioactive peptides are released in the infant intestine to modulate gut physiology through the
microbiome, intestinal epithelium, and immune system. Our specific aims are to determine the 1) antimicrobial
and bifidogenic activity, 2) intestinal epithelial cell (IEC)-specific effects (barrier function, proliferation,
differentiation) and 3) macrophage-immunomodulatory activity of peptides in the intestinal contents of preterm
infants fed human milk. For each of these activities, we will identify and validate specific peptides. Our approach
will be to collect intestinal samples from preterm neonates in the neonatal intensive care unit (NICU) after
feeding human milk, extract the peptide component from these samples, test their antibacterial, bifidogenic,
IEC-modulatory and macrophage-immunomodulatory activity in vitro, and identify candidate bioactive peptides
via mass spectrometry, database searching, and statistical techniques to be synthesized and tested for function.
As a sub-aim, we will perform this analysis for maternal and pasteurized donor human milk.
 This research is innovative because it identifies, for the first time, bioactivities of peptides released during
in vivo infant digestion, provides a means for identifying candidate bioactive peptides and establishes a pipeline
for testing candidate peptides in relevant model systems, including neonatal human enteroids. At the conclusion
of this project, we expect to 1) identify the gut health-related bioactivity of human milk protein-derived peptide
extracts from the preterm infant intestine and 2) identify specific peptides present in the infant intestine that can
modulate the microbiome, IECs, and macrophages. The positive impact of this research is that it will provide
the basis for leve...

## Key facts

- **NIH application ID:** 10926933
- **Project number:** 5R01HD109193-02
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Brian Scottoline
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $645,659
- **Award type:** 5
- **Project period:** 2023-09-15 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10926933

## Citation

> US National Institutes of Health, RePORTER application 10926933, Defining bioactivities of peptides released from human milk proteins in the preterm infant intestine (5R01HD109193-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10926933. Licensed CC0.

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