New Insights into Necrotizing Enterocolitis: From Laboratory Observation to Personalized Prevention and Treatment

Overview

Journal J Pediatr Surg

Specialties General Surgery
Pediatrics

Date 2018 Jul 8

PMID 29980346

Citations 46

Authors

David J Hackam

Chhinder P Sodhi

Misty Good

Affiliations

Soon will be listed here.

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.

Citing Articles

Piezo1 promotes the progression of necrotizing enterocolitis by activating the Ca2(+)/CaMKII-dependent pathway.

Li Z, Jiang Q, Wei J, Dang D, Meng Z, Wu H Commun Biol. 2025; 8(1):417.

PMID: 40074811 PMC: 11904196. DOI: 10.1038/s42003-025-07821-6.

Deoxycholic acid aggravates necrotizing enterocolitis through downregulation of mesenchymal-epithelial transition factor expression.

Li H, Lai J, Xiao D, Huang D, Zhang Y, Gu X Braz J Med Biol Res. 2024; 57:e14046.

PMID: 39630809 PMC: 11653493. DOI: 10.1590/1414-431X2024e14046.

Fresh Hemorrhages in Intestinal Resection Margins Are Associated with Unfavorable Clinical Outcomes in Preterm Infants with Necrotizing Enterocolitis with Surgical Intervention.

Schickedanz O, Friedmacher F, Gretser S, Braun Y, Wild P, Rolle U Life (Basel). 2024; 14(11).

PMID: 39598308 PMC: 11595751. DOI: 10.3390/life14111510.

Role of gut microbiome in developing necrotizing enterocolitis.

Karaca C, Takci H Folia Microbiol (Praha). 2024; 70(1):197-204.

PMID: 39550746 DOI: 10.1007/s12223-024-01217-5.

CSF1 is expressed by the intestinal epithelial cells to regulate Mφ macrophages and maintain epithelial homeostasis and is downregulated in neonates with necrotizing enterocolitis.

Sun X, Xu L, Ma S, Du J, Gu H, Wang J BMC Pediatr. 2024; 24(1):608.

PMID: 39342173 PMC: 11437640. DOI: 10.1186/s12887-024-05047-9.

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