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Updated: Jul 24, 2026
08:42
A Novel Human Epithelial Enteroid Model of Necrotizing Enterocolitis
Published on: April 10, 2019
Inflammation in the developing human intestine: A possible pathophysiologic contribution to necrotizing enterocolitis
N N Nanthakumar1, R D Fusunyan, I Sanderson
1Developmental Gastroenterology Laboratory, Combined Program in Pediatric Gastroenterology and Nutrition, Massachusetts General Hospital, Department of Pediatrics, Harvard Medical School, 149 13th Street, Charlestown, MA 02129, USA.
Summary
Immature infant intestines show an excessive inflammatory response to bacteria, contributing to necrotizing enterocolitis (NEC). This exaggerated interleukin-8 (IL-8) production in fetal cells, compared to mature cells, highlights a key factor in NEC development in premature infants.
Area of Science:
- Gastroenterology
- Neonatology
- Immunology
Background:
- Necrotizing enterocolitis (NEC) is a severe condition affecting premature infants, linked to gut bacteria and an immature intestinal response.
- The exact mechanisms underlying NEC pathogenesis, particularly the role of enterocyte signaling, require further elucidation.
Purpose of the Study:
- To investigate the hypothesis that an immature enterocyte response to bacterial stimuli contributes to NEC.
- To compare the interleukin-8 (IL-8) response to inflammatory stimuli in immature versus mature human small intestine.
Main Methods:
- In vitro studies using Caco-2 cells (mature enterocyte model) and primary human fetal intestinal cells (H4 cells).
- Exposure of both cell types to lipopolysaccharide (LPS) and IL-1beta, with measurement of IL-8 secretion and mRNA activity.
- Validation using small intestinal organ cultures from fetuses and older children, subjected to LPS and IL-1beta stimulation.
- Immunohistochemical staining to identify the cellular source of IL-8.
Main Results:
- Immature fetal cells exhibited significantly higher IL-8 secretion (8-fold for LPS, 20-fold for IL-1beta) and IL-8 mRNA activity compared to mature Caco-2 cells.
- Organ cultures confirmed greater IL-8 secretion (2.5-fold for LPS, 200-fold for IL-1beta) and elevated mRNA activity in fetal tissues.
- IL-8 was primarily localized in villous and crypt epithelium, with some presence in lymphoid cells.
Conclusions:
- Immature human enterocytes demonstrate an excessive pro-inflammatory cytokine (IL-8) response to inflammatory stimuli.
- This heightened response in premature infants may partially explain the development of necrotizing enterocolitis upon exposure to gut bacteria.
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