ArticlePediatric research2025
Butyrate protects the intestinal barrier by upregulating Fut2 expression via MEK4-JNK signaling pathway activation.
Article in Pediatric research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Fucosyltransferases in asthma: regulators of epithelial dysfunction, senescence, and airway inflammation.Clinical reviews in allergy & immunology · 2026Review
- The RNA-binding protein Imp1 promotes a Spdef transcriptional program and mucus fucosylation during necrotizing enterocolitis.American journal of physiology. Gastrointestinal and liver physiology · 2026Article
- FUT2-mediated α1,2-fucosylation in inflammatory bowel disease: mechanisms and translational potential.Molecular biology reports · 2026Review
- A case report of soluble A antigen confounding the blood type in a haplo-identical hematopoietic stem cell transplant patient with graft-versus-host disease.Transfusion · 2026Article
- Gentiana scabra mitigates Eimeria tenella-induced Coccidiosis by regulating the gut microbiota-metabolome and strengthening the intestinal barrier.Poultry science · 2026Article
- Article
- Oral delivery of enterocyte-mimetic butyrate-loaded nanoparticles repairs the gut barrier and inhibits growth of digestive system tumors.Nature communications · 2026Article
- Secretor status-dependent modulation ofFrontiers in nutrition · 2026Article
- The brain-bone-gut axis: a microbial bridge underlying multisystem comorbidities.Frontiers in endocrinology · 2026Review
- Succinate Promotes M1 Polarization of Intestinal Macrophages in Mice With Necrotizing Enterocolitis Through the PI3K/AKT Pathway.Pediatric discovery · 2025Article
- Maternal Dietary Fiber Intake During Lactation and Human Milk Oligosaccharide Fucosylation: a PRIMA Birth Cohort Study.Molecular nutrition & food research · 2025Article
- Unraveling the complexities of diet induced obesity and glucolipid dysfunction in metabolic syndrome.Diabetology & metabolic syndrome · 2025Review
- Role of C-Jun N-Terminal Kinases on a Stressed Epithelium: Time for Testing Isoform Specificity.Biology · 2025Review
- Predictive value of biomarkers in neonatal necrotizing enterocolitis.Frontiers in pediatrics · 2025Review
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundNecrotizing enterocolitis (NEC) is a severe gastrointestinal inflammatory disease in neonates. Fucosyltransferase 2 (Fut2) regulates intestinal epithelial cell fucosylation. In this study, we aimed to investigate butyrate-mediated upregulation of Fut2 expression and the underlying mechanisms.
methodsIn vivo and in vitro models were established. SP600125 was used to inhibit the MEK4-JNK pathway, and anisomycin was used to activate the MEK4-JNK pathway. Fut2, occludin, and ZO-1 expressions were assessed. Furthermore, intestinal permeability was analyzed by FITC-Dextran. The expression of proteins in the MEK-4-JNK pathway was examined by western blotting.
resultsIn vivo, the addition of exogenous butyrate notably upregulated Fut2, occludin, and ZO-1 expressions and reduced intestinal permeability in mice with NEC. Butyrate may increase the phosphorylation of MEK4, JNK, and c-jun, which are key components of the MEK4-JNK pathway. Additionally, SP600125 inhibited their phosphorylation, which was reversed by anisomycin treatment. In vitro, butyrate substantially increased occludin and ZO-1 expressions. Butyrate considerably increased Fut2 expression and markedly upregulated p-MEK4, p-JNK, and p-c-jun expressions. SP600125 administration decreased their expressions, while anisomycin administration increased their expressions.
conclusionButyrate upregulated Fut2 expression via activation of the MEK4-JNK pathway, improved intestinal barrier integrity, and protected neonatal mice from NEC. IMPACT: We found that exogenous butyrate could improve intestinal barrier integrity and protect against NEC in neonatal mice. Our data showed that exogenous butyrate supplementation upregulated Fut2 expression by activating the MEK4-JNK pathway. Our study provides novel insights into the pathogenesis of NEC, thereby laying an experimental foundation for future clinical research on the use of butyrate in NEC treatment.
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