# EFFECT OF COLOSTRUM ON GUT MATURATION AND HOST DEFENSE

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 1994 · $200,505

## Abstract

We will study the role of colostrum/breast milk in the host defense of
the GI tract.  Our overall hypothesis is that breast milk contains
factors that can actively stimulate the development of normal intestinal
mucosal barrier function in the newborn.  Specifically we plan to define
factors in breast milk/amniotic fluid which may:  1) influence the
expression of class II antigens on immature enterocytes; 2) affect
enterocyte microvillus membrane glycosylation and bacterial colonization
and 3) influence the expression of a fetal human small intestinal Fc
receptor (FcR) for maternal IgG.  We will also develop an immortal human
fetal small intestinal cell line to study these intestinal immaturities
and the effect of growth modulators on their maturation at the
cellular/molecular level.  During the previous funding period, we have
shown that:  1) maternal food antigens can enter breast milk and cause
colitis in some infants in the presence of breast milk lymphocytes and
cytokines; 2) that enterocytes from neonatal mice will express class II
(Ia) antigens after weaning; and 3) that this expression can be
prematurely displayed in the presence of inflammatory cytokines
(gammaINF).  In addition, we demonstrated that numerous non-immune host
defenses (MVM fluidity, antigen uptake, response to bacterial toxins and
bacterial colonization) are immature in the neonatal intestine and these
immaturities may be due to altered MVM protein/lipid composition,
glycosylation of glycoproteins/glycolipid and post receptor signal
transduction.  We also provide preliminary evidence that "growth factors"
in breast milk can induce a maturation of enterocyte immaturities
resulting in a decrease in the incidence of neonatal intestinal diseases
(necrotizing enterocolitis and toxigenic diarrhea).  Finally, we have
provided preliminary evidence that a "Fc" receptor for IgG antibodies
exists in the 18-20 week human fetal intestine (before the placental "Fc"
develops).  The human fetal intestinal FcR may be important in the
passive transfer of maternal IgG from amniotic fluid and preterm breast
milk to the fetal/neonatal circulation.  To accomplish the planned
research we have begun in vitro studies in intestinal cell lines and
primary human enterocyte organ/cell cultures of fetal, neonatal and
infant intestine and have begun studies to transfect fetal human
intestinal cells with viral oncogenes to render them immortal and capable
of differentiation.  Molecular approaches will be used to define in
enterocyte the role of growth modulators on:  1) the transcription and
translation of class II antigens; 2) the glycosyltransferase enzyme
activities in fetal/neonatal humans vs. older children; and 3) the
association of immature glycosylation on bacterial adherence to
intestinal glycoconjugates; 4) the mRNA/enzymatic activity of
glycosyltransferase.  Finally, we will try to isolate and characterize
the human fetal FcR on the small intestine, produce monoclonal antibodies
against it and...

## Key facts

- **NIH application ID:** 2196908
- **Project number:** 5R01HD012437-15
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **SAM.gov UEI:** FLJ7DQKLL226
- **Principal Investigator:** W ALLAN WALKER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $200,505
- **Award type:** 5
- **Project period:** 1979-05-01 → 1996-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2196908

## Citation

> US National Institutes of Health, RePORTER application 2196908, EFFECT OF COLOSTRUM ON GUT MATURATION AND HOST DEFENSE (5R01HD012437-15). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2196908. Licensed CC0.

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