Center for Molecular Medicine, UMC Utrecht, 3508 AB, Utrecht, the Netherlands.
Center for Molecular Medicine, UMC Utrecht, 3508 AB, Utrecht, the Netherlands.
Biochim Biophys Acta Mol Basis Dis. 2021 Nov 1;1867(11):166229. doi: 10.1016/j.bbadis.2021.166229. Epub 2021 Jul 28.
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）是一种常导致早产儿死亡的炎症性疾病。发育不完全的免疫系统在此疾病中发挥重要作用，但 NEC 发展的初始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成熟，营养物质和细菌能够破坏上皮细胞，并导致 NEC 中观察到的（不成熟）炎症反应、食物不耐受和吸收不良。肠道类器官研究表明，肠上皮细胞谱系的成熟是由两条关键信号通路：Wnt 和 Notch 来协调的。在 NEC 中，这些通路被 Toll 样受体 4 的过度激活所失调。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复杂联系。我们认为，调节这些通路的（营养）干预措施可能会降低早产儿患 NEC 的风险。
