New insights into necrotizing enterocolitis: From laboratory observation to personalized prevention and treatment

David J. Hackam, Chhinder P. Sodhi, Misty Good

Research output: Contribution to journalReview articlepeer-review

33 Scopus citations

Abstract

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. Conclusion: 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. Systematic Review: Level of Evidence: Level II.

Original languageEnglish
Pages (from-to)398-404
Number of pages7
JournalJournal of Pediatric Surgery
Volume54
Issue number3
DOIs
StatePublished - Mar 2019

Keywords

  • Breast milk
  • Innate immunity
  • Necrotizing enterocolitis (NEC)
  • Prematurity
  • Probiotics
  • Toll-like receptor 4 (TLR4)

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