Bile acid receptor FXR promotes intestinal epithelial ferroptosis and subsequent ILC3 dysfunction in neonatal necrotizing enterocolitis [scRNA-seq]
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE288751 | GEO | 2025/02/06
REPOSITORIES: GEO
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Project description:Necrotizing enterocolitis (NEC) is a prevalent pediatric emergency characterized by the sudden onset of intestinal ischemia and necrosis resulting from hyperinflammation.The interactions between the bile acid receptor FXR with gut microbiota and mucosal immunity in early postnatal life, and its exact role in the pathogenesis of NEC, are unknown.Here we analyze the role of FXR in IECs under NEC.
2025-02-02 | GSE288274 | GEO
Project description:Necrotizing enterocolitis (NEC) is a prevalent pediatric emergency characterized by the sudden onset of intestinal ischemia and necrosis resulting from hyperinflammation.The interactions between the bile acid receptor FXR with gut microbiota and mucosal immunity in early postnatal life, and its exact role in the pathogenesis of NEC, are unknown.Here we analyze the role of FXR in IECs under NEC.
2025-02-06 | GSE288979 | GEO
Project description:Necrotizing enterocolitis (NEC) is a prevalent pediatric emergency characterized by the sudden onset of intestinal ischemia and necrosis resulting from hyperinflammation.The interactions between the bile acid receptor FXR with gut microbiota and mucosal immunity in early postnatal life, and its exact role in the pathogenesis of NEC, are unknown.Here we analyze the role of FXR in IECs under NEC.
2025-02-06 | GSE288754 | GEO
Project description:Necrotizing enterocolitis (NEC) is a devastating inflammatory bowel necrosis of very preterm infants with limited therapeutic approaches. Mounting evidence supports the role of Piezo1, a widely distributed mechanosensor on intestinal epithelial cells (IECs), in intestinal inflammation, but its underlying mechanism in the development of NEC has not been explored. Here we demonstrated that Piezo1 protein expression was higher in very preterm infants compared to full-term infants, and positively associated with serum inflammation levels in NEC patients. C57BL/6J mice in which Piezo1 was selectively deleted IECs (villin specific knockout; CKO) and floxed control mice were subjected to induce NEC, and Piezo1 regulated intestinal barrier function, restricted cytokines secretion, and diminished the inflammatory response in NEC mouse models.
2025-02-17 | GSE283887 | GEO
Project description:Group 3 innate lymphoid cells (ILC3s) play a crucial role in intestinal inflammatory disorders such as necrotizing enterocolitis (NEC) in neonates; however, the mechanisms by which ILC3s contribute to NEC remain unclear. In this study, single-cell transcriptomics, in vivo experiments on T cell-deficient mice, and targeted cell interventions demonstrated that NKp46−CCR6− (double-negative, DN) ILC3 autophagy significantly impacts NEC development by regulating intracellular metabolism. Mice lacking ATG5 or treated with autophagy inhibitors exhibited reduced ILC3 abundance and impaired ILC3 function, alleviating NEC. Mechanistically, ATG5 deficiency enhanced fatty acid metabolism while reducing glycolysis. Conversely, inhibiting fatty acid oxidation or supplementing with lactate restored the quantity and functionality of ATG5-deficient DN ILC3s, exacerbating NEC. Lipid metabolism analyses combined with a mouse model of NEC indicated that phosphatidylcholine supplementation alleviated intestinal inflammation by inhibiting DN ILC3 autophagy. Clinically, patients with NEC showed elevated ILC3 levels and significant enrichment of autophagy genes. These findings highlight the importance of DN ILC3 autophagy in metabolic adaptation, suggesting potential strategies for managing NEC.
2026-04-12 | GSE306398 | GEO
Project description:Group 3 innate lymphoid cells (ILC3s) play a crucial role in intestinal inflammatory disorders such as necrotizing enterocolitis (NEC) in neonates; however, the mechanisms by which ILC3s contribute to NEC remain unclear. In this study, single-cell transcriptomics, in vivo experiments on T cell-deficient mice, and targeted cell interventions demonstrated that NKp46−CCR6− (double-negative, DN) ILC3 autophagy significantly impacts NEC development by regulating intracellular metabolism. Mice lacking ATG5 or treated with autophagy inhibitors exhibited reduced ILC3 abundance and impaired ILC3 function, alleviating NEC. Mechanistically, ATG5 deficiency enhanced fatty acid metabolism while reducing glycolysis. Conversely, inhibiting fatty acid oxidation or supplementing with lactate restored the quantity and functionality of ATG5-deficient DN ILC3s, exacerbating NEC. Lipid metabolism analyses combined with a mouse model of NEC indicated that phosphatidylcholine supplementation alleviated intestinal inflammation by inhibiting DN ILC3 autophagy. Clinically, patients with NEC showed elevated ILC3 levels and significant enrichment of autophagy genes. These findings highlight the importance of DN ILC3 autophagy in metabolic adaptation, suggesting potential strategies for managing NEC.
2026-04-12 | GSE319269 | GEO
Project description:Group 3 innate lymphoid cells (ILC3s) play a crucial role in intestinal inflammatory disorders such as necrotizing enterocolitis (NEC) in neonates; however, the mechanisms by which ILC3s contribute to NEC remain unclear. In this study, single-cell transcriptomics, in vivo experiments on T cell-deficient mice, and targeted cell interventions demonstrated that NKp46−CCR6− (double-negative, DN) ILC3 autophagy significantly impacts NEC development by regulating intracellular metabolism. Mice lacking ATG5 or treated with autophagy inhibitors exhibited reduced ILC3 abundance and impaired ILC3 function, alleviating NEC. Mechanistically, ATG5 deficiency enhanced fatty acid metabolism while reducing glycolysis. Conversely, inhibiting fatty acid oxidation or supplementing with lactate restored the quantity and functionality of ATG5-deficient DN ILC3s, exacerbating NEC. Lipid metabolism analyses combined with a mouse model of NEC indicated that phosphatidylcholine supplementation alleviated intestinal inflammation by inhibiting DN ILC3 autophagy. Clinically, patients with NEC showed elevated ILC3 levels and significant enrichment of autophagy genes. These findings highlight the importance of DN ILC3 autophagy in metabolic adaptation, suggesting potential strategies for managing NEC.
2026-04-12 | GSE306522 | GEO
Project description:<p>The Neonatal Microbiome and Necrotizing enterocolitis (NEC) study is a multi-centered case control study testing the hypothesis that NEC is a direct or indirect consequence of the enteric biomass, its products, or both. Very low birth weight infants (VLBW; birth weight ≤ 1500 grams) admitted to the neonatal intensive care unit are prospectively followed over the first 5 week or until they reach 36 weeks gestation, whichever occurs later. VLBW infants with a lethal clinical condition are excluded. Over the course of the study period, prospective samples are obtained on all infants, and include all stools, and weekly blood samples, palm and oral swabs. Clinical data is collected over the course of the entire hospitalization. Cases are identified based on Bell's staging for NEC, requiring Bell's stage II (abdominal clinical signs and radiographic evidence of pneumatosis, portal venous gas or pneumoperitoneum). Controls are identified from the pool of prospectively enrolled subjects, matching for gestational age, birth weight, post-natal age and birth date.</p> <p>The microbial components of stool and its products before and at the onset of NEC, are then compared between cases and controls.</p> <p>The Aims of this proposal are to (1) conduct a case cohort study in which we compare clinical data and biological specimens from cases and well-matched controls; (2) determine if the kind and density of intestinal biomass, its gene content, and transcriptional activity are associated with, and potential determinants of, NEC; and (3) determine if host risk alleles for intestinal inflammation play a role in the development of NEC.</p>
| phs000247.v2.p2 | EGA
Project description:Bile acid receptor FXR promotes intestinal epithelial ferroptosis and subsequent ILC3 dysfunction in neonatal necrotizing enterocolitis [scRNA-seq]
| PRJNA1219193 | ENA
Project description:Preterm neonates are susceptible to gastrointestinal (GI) disorders such as necrotizing enterocolitis (NEC). Maternal milk, and especially colostrum, protects against NEC via growth promoting, immunomodulatory and antimicrobial factors. The fetal enteral diet, amniotic fluid (AF), contains similar bioactive components and we hypothesized that postnatal AF administration would reduce inflammatory responses and NEC in preterm neonates. Thirty preterm pigs (92% gestation) were delivered by caesarean section and fed total parental nutrition (TPN) for 48 h followed by enteral porcine colostrum (COLOS, n=7), infant formula (FORM, n=13) or formula + porcine AF (AF, n=10). Using a previously validated model of NEC in preterm pigs, we determined the structural, functional, microbiological and immunological responses to AF when administered prior to and after introduction of a suboptimal enteral formula diet. Keywords: Healthy versus inflammed tissues in relation to necrotizing enterocolitis Pigs from each treatment group (COLOS, n=4; FORM, n=6; and AF, n=7) were randomly selected for microarray analysis of frozen distal small intestine samples. The FORM group was further divided into formula-fed healthy pigs (F-HEA, n=3) and formula-fed NEC pigs (F-NEC, n=3) in order to compare sick versus healthy formula fed pigs. Equal amounts of total distal small intestinal RNA from all pigs were pooled to make the reference sample. Samples and reference pool were labelled with Oyster 550 and 650, respectively. The in-house spotted porcine oligonucleotide microarray version 4 (POM4) is a low density microarray consisting of 384 different oligonucleotide probes representing more than 200 different immune related genes.
2010-05-06 | E-GEOD-13515 | biostudies-arrayexpress