1. Breast milk nutrients driving intestinal epithelial layer maturation via Wnt and Notch signaling: Implications for necrotizing enterocolitis.
- Author
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de Jong JCW, Ijssennagger N, and van Mil SWC
- Subjects
- Breast Feeding, Enterocolitis, Necrotizing metabolism, Enterocolitis, Necrotizing prevention & control, Humans, Infant, Newborn, Infant, Premature, Intestinal Mucosa metabolism, Milk, Human chemistry, Receptors, Notch antagonists & inhibitors, Receptors, Notch metabolism, Signal Transduction drug effects, Signal Transduction physiology, Toll-Like Receptor 4 antagonists & inhibitors, Toll-Like Receptor 4 metabolism, Wnt Proteins antagonists & inhibitors, Wnt Proteins metabolism, Wnt Signaling Pathway drug effects, Wnt Signaling Pathway physiology, Enterocolitis, Necrotizing pathology, Intestinal Mucosa pathology, Milk, Human metabolism, Nutrients metabolism
- Abstract
Necrotizing enterocolitis (NEC) is an often lethal, inflammatory disease of the preterm intestine. The underdeveloped immune system plays an important role; however, the initial trigger for NEC development is likely a damaged intestinal epithelial layer. We hypothesize that due to incomplete maturation of different epithelial cell lineages, nutrients and bacteria are able to damage the epithelial cells and cause the (immature) inflammatory response, food intolerance and malabsorption seen in NEC. Intestinal organoid research has shown that maturation of intestinal epithelial cell lineages is orchestrated by two key signaling pathways: Wnt and Notch. In NEC, these pathways are dysregulated by hyperactivation of Toll-like-receptor-4. Breastfeeding decreases the risk of developing NEC compared to formula milk. Here, we review the intricate link between breast milk components, Wnt and Notch signaling and intestinal epithelial maturation. We argue that (nutritional) interventions regulating these pathways may decrease the risk of NEC development in preterm infants., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)
- Published
- 2021
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