# Novel Strategies for Prevention of Necrotizing Enterocolitis

> **NIH NIH P20** · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · 2020 · $282,826

## Abstract

Project Summary
 Necrotizing enterocolitis (NEC) is one of the most common gastrointestinal emergency in the neonatal
period. It is characterized by severe intestinal inflammation that can rapidly result in intestinal necrosis, sepsis,
and potentially death. Despite advances in medical care, mortality and morbidity caused by NEC has not
changed. This is largely due to the poor understanding of the complex pathogenesis, the limitations of the current
animal models, and the lack of specific therapeutic or preventative therapies.
 Although the etiology is unclear, evidence suggests that prematurity, formula feeding, altered intestinal
microbiome, and hypoxia-ischemia play major roles in NEC. Preterm infants have impaired intestinal
permeability, and exhibit prominent intestinal epithelial TLR4 expression; all of which render the bowel at risk of
bacterial translocation, an exaggerated inflammatory response, and NEC development. Therefore, identifying
strategies or interventions that promote maturation of intestinal defenses, epithelial integrity, and modulate
inflammation is critical in preventing this deadly disease.
 We have promising preliminary data demonstrating that oral hyaluronan at a molecular weight of ~ 35
kDa (HA 35kDa) reduces mortality, severity of intestinal injury, and systemic inflammation in a murine model of
NEC. HA is a glycosaminoglycan found in almost all tissues including extracellular matrix. Studies showed that
HA isolated from breast milk or commercially available HA 35kDA, protects against bacteria-induced colitis by
increasing the expression of antimicrobial β-defensins, and tight junction protein ZO-1 in colonic epithelium in
vivo and in vitro. Based on our preliminary data and the previously reported biological effects of HA in the large
intestine, we propose to directly investigate the effect of HA 35kDa on the (1) immature intestinal defenses,
specifically antimicrobial peptides produced by enterocytes and Paneth cells, (2) intestinal barrier including
mucous lining and TJ formation, and (3) on the development of the intestinal microbiome in healthy pups and
pups with NEC (Aim 1).To facilitate translation of our results to human studies, we propose to evaluate the effect
of HA 35kDa on a novel premature non-human primate model (NHP) of NEC (Aim 2).
 The ultimate goal of this project to initiate a new research direction in a disease that has shown little
clinical progress over the past 50 years. Results from our study would enhance our understanding of NEC and
lead to identification of new preventative strategies that will improve patient outcomes.

## Key facts

- **NIH application ID:** 9853462
- **Project number:** 1P20GM134973-01
- **Recipient organization:** UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
- **Principal Investigator:** Hala Chaaban
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $282,826
- **Award type:** 1
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9853462

## Citation

> US National Institutes of Health, RePORTER application 9853462, Novel Strategies for Prevention of Necrotizing Enterocolitis (1P20GM134973-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9853462. Licensed CC0.

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