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Indole-3-carbinol-dependent aryl hydrocarbon receptor signaling attenuates the inflammatory response in experimental necrotizing enterocolitis

ABSTRACT: Indole-3-carbinol-dependent aryl hydrocarbon receptor signaling attenuates the inflammatory response in experimental necrotizing enterocolitis

PROVIDER: PRJNA646868 | ENA |

REPOSITORIES: ENA

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Indole-3-carbinol-dependent aryl hydrocarbon receptor signaling attenuates the inflammatory response in experimental necrotizing enterocolitis

Project description:Necrotizing enterocolitis (NEC) causes significant morbidity and mortality in premature infants; therefore, the identification of therapeutic and preventative strategies against NEC remains a high priority. The ligand-dependent transcription factor aryl hydrocarbon receptor (AhR) is well known to contribute to the regulation of intestinal microbial communities and amelioration of intestinal inflammation. However, the role of AhR signaling in NEC is unclear. Experimental NEC was induced in four-day-old wild-type mice or mice lacking AhR expression in the intestinal epithelial cells (AhRΔrIEC) or in CD11c+ cells (AhRΔrCD11c) by subjecting animals to twice daily hypoxic stress and gavage feeding with formula supplemented with lipopolysaccharide and enteric bacteria. During NEC, compared to wild-type mice treated with vehicle, littermates treated with an AhR pro-ligand, indole-3-carbinol (I3C), had reduced expression of Il1b and Marco, a scavenger receptor that mediates dendritic cell activation and the recognition and clearance of bacterial pathogens by macrophages. Furthermore, I3C treatment lead to the downregulation of genes involved in cytokine and chemokine as revealed by pathway enrichment analysis. AhRΔrIEC and their cre-negative mouse littermates were similarly susceptible to experimental NEC, whereas AhRΔrCD11c mice with NEC exhibited heightened inflammatory responses compared to their cre-negative mouse littermates. In seeking to determine the mechanisms involved in this increased inflammatory response, we identified the Tim-4- monocyte-dependent subset of macrophages as increased in AhRΔrCD11c mice compared to their cre-negative littermates. Taken together, these findings demonstrate the potential for AhR ligands as a novel immunotherapeutic approach to the management of this devastating disease.

2021-03-03 | GSE154617 | GEO

Microfluidic Device Facilitates In Vitro Modeling of Human Neonatal Necrotizing Enterocolitis-on-a-Chip

Project description:Necrotizing enterocolitis is an intestinal disease induces rapid destruction of the epithelial monolayer of the neonatal intestine. Clinically relevant models of this disease are lacking. Using our novel microfluidic model of necrotizing enterocolitis, we characterized the response of intestinal epithelial cell-derived organoids to intestinal bacteria isolated from a neonate with fatal NEC. We subsequently used RNA-sequencing to determine the gene expression profile of these cells after 24 or 72 hours of incubation.

2023-06-14 | GSE226086 | GEO

Amniotic fluid and necrotizing enterocolitis in preterm pigs

2010-03-01 | GSE13515 | GEO

Amniotic fluid and necrotizing enterocolitis in preterm pigs

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

The Neonatal Microbiome and Necrotizing Enterocolitis

Project description:The Neonatal Microbiome and Necrotizing Enterocolitis

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Effect of formula feeding and hypoxia on Necrotizing Enterocolitis (NEC) development

Project description:Necrotizing Enterocolitis (NEC) is an inflammation causing injury to the bowel in newborns. This project uses a rodent model that mimics the intestinal pathological changes seen in NEC to study the effect of formula feeding and hypoxia on NEC development Keywords: time series, diet, hypoxia

2003-07-16 | GSE491 | GEO

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Project description:Quantification of proteins in the ileum of Necrotizing enterocolitis.

2022-04-27 | PXD025647 | JPOST Repository

Transcription profiling time series of the effects of hypoxia, breast and formula feeding on a Rattus norvegicus model of necrotizing enterocolitis

2007-10-11 | E-GEOD-491 | biostudies-arrayexpress

Temporal development of necrotizing enterocolitis in the preterm pig

Project description:Necrotizing enterocolitis (NEC), a serious gastrointestinal disease that afflicts 5-10% of preterm infants, often progresses rapidly from mild food intolerance into extensive haemorrhage, inflammation and necrosis. Events leading to NEC have remained poorly defined. Similar disease characteristics are observed in preterm pigs 24-48 h after feeding formula. Using this model, we aimed to characterize the temporal development of NEC, and describe the functional and immunological response of the preterm intestine preceding NEC. Keywords: time course

2010-03-01 | GSE13516 | GEO

Neonatal necrotizing enterocolitis-associated DNA methylation signatures in the colon are evident in stool samples of affected individuals

Project description:Neonatal necrotizing enterocolitis (NEC) is a deadly and unpredictable gastrointestinal disease, for which no biomarkers exist. We aimed to describe the methylation patterns in stool and colon from infants with NEC.

2022-09-13 | GSE212997 | GEO

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