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Updated: Feb 2, 2026

A Novel Human Epithelial Enteroid Model of Necrotizing Enterocolitis
Published on: April 10, 2019
Human Milk Oligosaccharides Increase Mucin Expression in Experimental Necrotizing Enterocolitis
Richard You Wu1,2, Bo Li3, Yuhki Koike3
1Cell Biology Program, Research Institute, Division of Gastroenterology, Hepatology and Nutrition, Hospital for Sick Children, Toronto, Ontario, Canada.
Human milk oligosaccharides (HMOs) protect preterm infants from necrotizing enterocolitis (NEC) by increasing intestinal mucin levels. This study identifies protein disulfide isomerase (PDI) as a key mediator in HMO-induced gut protection.
Area of Science:
- Neonatal research
- Gastroenterology
- Immunology
Background:
- Necrotizing enterocolitis (NEC) is a critical threat to preterm infant survival, with higher incidence in formula-fed infants.
- Human milk oligosaccharides (HMOs) are known to reduce NEC incidence, but the protective mechanisms remain elusive.
Purpose of the Study:
- To investigate the impact of HMOs on intestinal mucin levels in a murine NEC model.
- To elucidate the molecular mechanisms by which HMOs confer protection against NEC.
Main Methods:
- HMOs were extracted from human breast milk and administered to a murine NEC model.
- Human intestinal epithelial cells and organoids were used to validate findings in vitro.
- Mucin expression, intestinal permeability, bacterial attachment, and protein disulfide isomerase (PDI) activity were evaluated.
Main Results:
- HMO administration increased Muc2 mucin levels and reduced intestinal permeability in pups.
- HMO-treated cells exhibited enhanced Muc2 expression, reduced bacterial adhesion, and decreased permeability.
- HMOs were shown to directly induce chaperone protein PDI expression, which is crucial for HMO-mediated protection.
Conclusions:
- HMOs protect the neonatal intestine by upregulating mucin production.
- Protein disulfide isomerase (PDI) is a key mediator in the protective effects of HMOs against NEC.
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