Necrotizing enterocolitis as a disorder of neonatal mucosal immune ecology: from dysbiosis and barrier failure to regulated cell death and precision prevention
4 affiliations
- 1Reproductive Prenatal Genetic Center, First Hospital of Jilin University
- 2China-Japan Union Hospital of Jilin University
- 3Department of Neonatology, First Hospital of Jilin University
- 4Department of Cardiology, First Hospital of Jilin University
Abstract
Necrotizing enterocolitis (NEC) remains one of the most severe gastrointestinal emergencies of prematurity. Although survival of extremely preterm infants has improved, NEC continues to cause substantial mortality, intestinal failure, neurodevelopmental impairment, and prolonged neonatal intensive care. Its pathogenesis has traditionally been described as a convergence of prematurity, enteral feeding, intestinal ischemia, and abnormal bacterial colonization. This model remains useful, but it does not fully explain why only a subset of high-risk infants develop NEC or why single interventions show inconsistent benefit. This narrative review examines classic preterm NEC as a disorder of neonatal mucosal immune ecology, while distinguishing it from spontaneous intestinal perforation and predominantly hemodynamic injury in congenital heart disease. Epithelial immaturity, dysbiosis, altered microbial metabolism, exaggerated pattern-recognition signaling, immune-cell activation, endothelial dysfunction, thromboinflammation, and regulated cell death amplify one another. Particular attention is given to cell-specific signaling, the interaction of vascular and epithelial injury, and the distinction between protective autophagy and destructive stress responses. These mechanisms inform translational opportunities involving mother’s own milk, donor human milk, strain-specific probiotics, postbiotics, defined microbial metabolites, extracellular vesicles, organoids, and multi-omics biomarkers. A mucosal immune-ecology model supports precision prevention based on developmental timing, microbial function, immune state, and injury mechanism.
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BibTeX
@article{sun2026necrotizing,
title = {{Necrotizing enterocolitis as a disorder of neonatal mucosal immune ecology: from dysbiosis and barrier failure to regulated cell death and precision prevention}},
author = {Shaohang Sun and Zekun Yu and Meimei Zhou and Minghua Li and Shuyi Wang and Yuqi Cheng and Yihan Qu and Chaoying Yan and Jiayi Tian},
journal = {Frontiers in Immunology},
year = {2026},
month = nov,
doi = {10.3389/fimmu.2026.1963418},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1963418/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Necrotizing enterocolitis as a disorder of neonatal mucosal immune ecology: from dysbiosis and barrier failure to regulated cell death and precision prevention
AU - Shaohang Sun
AU - Zekun Yu
AU - Meimei Zhou
AU - Minghua Li
AU - Shuyi Wang
AU - Yuqi Cheng
AU - Yihan Qu
AU - Chaoying Yan
AU - Jiayi Tian
PY - 2026
DA - 2026/11/02
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1963418
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1963418/full
AB - Necrotizing enterocolitis (NEC) remains one of the most severe gastrointestinal emergencies of prematurity. Although survival of extremely preterm infants has improved, NEC continues to cause substantial mortality, intestinal failure, neurodevelopmental impairment, and prolonged neonatal intensive care. Its pathogenesis has traditionally been described as a convergence of prematurity, enteral feeding, intestinal ischemia, and abnormal bacterial colonization. This model remains useful, but it does not fully explain why only a subset of high-risk infants develop NEC or why single interventions show inconsistent benefit. This narrative review examines classic preterm NEC as a disorder of neonatal mucosal immune ecology, while distinguishing it from spontaneous intestinal perforation and predominantly hemodynamic injury in congenital heart disease. Epithelial immaturity, dysbiosis, altered microbial metabolism, exaggerated pattern-recognition signaling, immune-cell activation, endothelial dysfunction, thromboinflammation, and regulated cell death amplify one another. Particular attention is given to cell-specific signaling, the interaction of vascular and epithelial injury, and the distinction between protective autophagy and destructive stress responses. These mechanisms inform translational opportunities involving mother’s own milk, donor human milk, strain-specific probiotics, postbiotics, defined microbial metabolites, extracellular vesicles, organoids, and multi-omics biomarkers. A mucosal immune-ecology model supports precision prevention based on developmental timing, microbial function, immune state, and injury mechanism.
SN - 1664-3224
ER -