Hackam David J, Sodhi Chhinder P, Good Misty
Division of Pediatric Surgery and the Department of Surgery at the Johns Hopkins University, Baltimore, Maryland.
Division of Pediatric Surgery and the Department of Surgery at the Johns Hopkins University, Baltimore, Maryland.
J Pediatr Surg. 2019 Mar;54(3):398-404. doi: 10.1016/j.jpedsurg.2018.06.012. Epub 2018 Jun 18.
BACKGROUND/PURPOSE: Necrotizing enterocolitis (NEC) is a devastating disease of prematurity that develops after feeding, often without warning, and results in diffuse intestinal necrosis leading to sepsis and death in many cases. The lack of improvement in overall survival is influenced by nonspecific diagnostic modalities as well as inexact and nonpersonalized treatment strategies.
METHODS/RESULTS: Recently, we and others have shown that NEC develops in response to exaggerated bacterial signaling in the premature intestine, as a consequence of elevated expression and activity of the bacterial receptor toll-like receptor 4 (TLR4), which is important for normal gut development. Breast milk is a powerful TLR4 inhibitor, while mutations in TLR4 genes lead to increased NEC risk in humans, providing proof-of-concept for its role in NEC. Recently, a drug discovery approach has revealed a novel class of TLR4 inhibitors which are being developed for personalized approaches to NEC treatment.
This review will highlight the current understanding of the role of bacterial signaling in NEC pathogenesis, and will describe advances in diagnosis, prevention and treatment of NEC that may hopefully improve survival for these most fragile patients.
Level of Evidence: Level II.
背景/目的：坏死性小肠结肠炎（NEC）是一种严重的早产儿疾病，常在喂养后发生，且往往毫无征兆，会导致弥漫性肠坏死，在许多情况下会引发败血症并导致死亡。总体生存率缺乏改善受到非特异性诊断方式以及不精确和非个性化治疗策略的影响。
方法/结果：最近，我们和其他研究表明，NEC是由于早产肠道中细菌信号过度激活而引发的，这是细菌受体Toll样受体4（TLR4）表达和活性升高的结果，而TLR4对正常肠道发育很重要。母乳是一种强大的TLR4抑制剂，而TLR4基因突变会增加人类患NEC的风险，这为其在NEC中的作用提供了概念验证。最近，一种药物研发方法揭示了一类新型的TLR4抑制剂，正在开发用于NEC个性化治疗方法。
本综述将重点阐述目前对细菌信号在NEC发病机制中作用的理解，并描述NEC在诊断、预防和治疗方面的进展，有望改善这些最脆弱患者的生存率。
证据水平：二级。
