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.

坏死性小肠结肠炎 (NEC) 是一种常见的致命性早产肠道炎症性疾病。不发达的免疫系统起着重要作用；然而，NEC 发展的最初触发因素可能是受损的肠上皮层。我们假设，由于不同上皮细胞谱系的不完全成熟，营养物质和细菌能够损伤上皮细胞并导致 NEC 中看到的（不成熟的）炎症反应、食物不耐受和吸收不良。肠道类器官研究表明，肠道上皮细胞谱系的成熟是由两个关键信号通路协调的：Wnt 和 Notch。在 NEC 中，这些通路因 Toll 样受体 4 的过度激活而失调。

与配方奶相比，母乳喂养可降低患 NEC 的风险。在这里，我们回顾了母乳成分、Wnt 和 Notch 信号与肠上皮成熟之间的错综复杂的联系。我们认为，调节这些途径的（营养）干预措施可能会降低早产儿发生 NEC 的风险。