Necrotizing enterocolitis (NEC) is the leading cause of death and disability from gastrointestinal disease in premature infants. Recent discoveries have shed light on a unifying theorem to explain the pathogenesis of NEC, suggesting that specific treatments might finally be forthcoming. A variety of experiments have highlighted how the interaction between bacterial signalling receptors on the premature intestine and an abnormal gut microbiota incites a pro-inflammatory response in the intestinal mucosa and its underlying endothelium that leads to NEC. Central amongst the bacterial signalling receptors implicated in NEC development is the lipopolysaccharide receptor Toll-like receptor 4 (TLR4), which is expressed at higher levels in the premature gut than in the full-term gut. The high prenatal intestinal expression of TLR4 reflects the role of TLR4 in the regulation of normal gut development, and supports additional studies indicating that NEC develops in response to signalling events that occur in utero. This Review provides new evidence explaining the pathogenesis of NEC, explores new findings indicating that NEC development has origins before birth, and discusses future questions and opportunities for discovery in this field.

坏死性小肠结肠炎 (NEC) 是早产儿胃肠道疾病导致死亡和残疾的主要原因。最近的发现揭示了一个统一的定理来解释 NEC 的发病机制，这表明最终可能会出现特定的治疗方法。各种实验强调了早产肠上的细菌信号受体与异常肠道微生物群之间的相互作用如何在肠粘膜及其下层内皮中引发促炎反应，从而导致 NEC。与 NEC 发展有关的细菌信号受体的核心是脂多糖受体 Toll 样受体 4 (TLR4)，它在早产肠道中的表达水平高于足月肠道。TLR4 的高产前肠道表达反映了 TLR4 在调节正常肠道发育中的作用，并支持其他研究表明 NEC 是响应子宫内发生的信号事件而发展的。这篇综述提供了解释 NEC 发病机制的新证据，探讨了表明 NEC 发展在出生前就有起源的新发现，并讨论了该领域未来的问题和发现机会。