ArticleCellular and molecular gastroenterology and hepatology2020
A Novel Role for Necroptosis in the Pathogenesis of Necrotizing Enterocolitis.
Article in Cellular and molecular gastroenterology and hepatology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers, 2 of them syntheses that pooled it.
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Who cites it
67 citing papers in PubMed, 2 syntheses or guidelines pooled it, 106 citations in OpenAlex.
- Research focus and emerging trends of the gut microbiome and infant: a bibliometric analysis from 2004 to 2024.Frontiers in microbiology · 2024Pooled it
- Enteral Feeding Interventions in the Prevention of Necrotizing Enterocolitis: A Systematic Review of Experimental and Clinical Studies.Nutrients · 2021Pooled it
- 2'-Fucosyllactose Effects on Preterm Growth, Tolerance, and Neurobehavior: A Double-Blind, Randomized, Placebo-Controlled Pilot.Nutrients · 2026Trial
- Infants Fed Breastmilk or 2'-FL Supplemented Formula Have Similar Systemic Levels of Microbiota-Derived Secondary Bile Acids.Nutrients · 2023Trial
- NEC-Associated Bronchopulmonary Dysplasia and the Gut-Lung Axis in Preterm Infants.American journal of perinatology · 2026Review
- Necrotizing enterocolitis.Nature reviews. Disease primers · 2026Review
- Gut-microbiota-derived 3-indoleacrylic acid alleviates neonatal necrotizing enterocolitis by inhibiting epithelial necroptosis.Cell reports. Medicine · 2026Article
- Risk factors for necrotizing enterocolitis in preterm infants: a 1:1 matched case-control study.Frontiers in pediatrics · 2026Article
- Digging deeper into necrotizing enterocolitis: bridging clinical, microbial, and molecular perspectives.Gut microbes · 2025Review
- The microbiome's hidden influence: preclinical insights into inflammatory responses in necrotizing enterocolitis.Seminars in immunopathology · 2025Review
- Multi-strain probiotic administration decreases necrotizing enterocolitis severity and alters the epigenetic profile in mice.Pediatric research · 2025Article
- An early post-birth immune-microbiota landscape predicts the development of necrotizing enterocolitis in term newborns with congenital heart defects.Scientific reports · 2025Article
- Necrotizing Enterocolitis: A Comprehensive Review on Toll-like Receptor 4-Mediated Pathophysiology, Clinical, and Therapeutic Insights.Biomedicines · 2025Review
- Identification of potential necroinflammation-associated necroptosis-related biomarkers in necrotizing enterocolitis based on bioinformatics analysis and machine learning.Translational pediatrics · 2025Article
- A developmental role for toll like receptor 4 in the neonatal intestine.Pediatric research · 2025Article
- Human milk extracellular vesicles modulate inflammation and cell survival in intestinal and immune cells.Pediatric research · 2025Article
- Portal venous gas value in predicting surgical necrotizing enterocolitis.Pediatric research · 2025Article
- Comparative gastrointestinal organoid models across species: A Zoobiquity approach for precision medicine.Regenerative therapy · 2025Review
- N-Acetylcysteine Alleviates Necrotizing Enterocolitis by Depressing SESN2 Expression to Inhibit Ferroptosis in Intestinal Epithelial Cells.Inflammation · 2025Article
- Necrotising enterocolitis biomarkers: a systematic review.Frontiers in pediatrics · 2025Review
7 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 3 institutions in 1 country.
Funding
Abstract
BACKGROUND &
aimsNecrotizing enterocolitis (NEC) is a devastating disease of premature infants characterized by Toll-like receptor 4 (TLR4)-dependent intestinal inflammation and enterocyte death. Given that necroptosis is a proinflammatory cell death process that is linked to bacterial signaling, we investigated its potential role in NEC, and the mechanisms involved.
methodsHuman and mouse NEC intestine were analyzed for necroptosis gene expression (ie, RIPK1, RIPK3, and MLKL), and protein activation (phosphorylated RIPK3). To evaluate a potential role for necroptosis in NEC, the effects of genetic (ie, Ripk3 knockout or Mlkl knockout) or pharmacologic (ie, Nec1s) inhibition of intestinal inflammation were assessed in a mouse NEC model, and a possible upstream role of TLR4 was assessed in Tlr4-deficient mice. The NEC-protective effects of human breast milk and its constituent milk oligosaccharides on necroptosis were assessed in a NEC-in-a-dish model, in which mouse intestinal organoids were cultured as either undifferentiated or differentiated epithelium in the presence of NEC bacteria and hypoxia.
resultsNecroptosis was activated in the intestines of human and mouse NEC in a TLR4-dependent manner, and was up-regulated specifically in differentiated epithelium of the immature ileum. Inhibition of necroptosis genetically and pharmacologically reduced intestinal-epithelial cell death and mucosal inflammation in experimental NEC, and ex vivo in the NEC-in-a-dish system. Strikingly, the addition of human breast milk, or the human milk oligosaccharide 2 fucosyllactose in the ex vivo system, reduced necroptosis and inflammation.
conclusionsNecroptosis is activated in the intestinal epithelium upon TLR4 signaling and is required for NEC development, and explains in part the protective effects of breast milk.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.