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Formula Feeding and Immature Gut Microcirculation Promote Intestinal Hypoxia leading to Necrotizing Enterocolitis

ABSTRACT: Formula Feeding and Immature Gut Microcirculation Promote Intestinal Hypoxia leading to Necrotizing Enterocolitis

PROVIDER: PRJNA576714 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR10254942_1.fastq.gz	Fastqsanger.gz
	SRR10254942_2.fastq.gz	Fastqsanger.gz
	SRR10254943_1.fastq.gz	Fastqsanger.gz
	SRR10254943_2.fastq.gz	Fastqsanger.gz
	SRR10254944_1.fastq.gz	Fastqsanger.gz

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Formula Feeding and Immature Gut Microcirculation Promote Intestinal Hypoxia leading to Necrotizing Enterocolitis

Project description:Major risk factors for necrotizing enterocolitis (NEC) are formula feeding and prematurity, however, their pathogenic mechanisms are unknown. We found that insufficient arginine/nitric oxide synthesis limits blood flow in the intestinal microvasculature, leading to hypoxia, mucosa damage and NEC in the premature intestine after formula feeding. Formula feeding led to increased intestinal hypoxia in pups at postnatal day 1(P1) and P5, but not in more mature pups at P9. Accordingly, blood flow in the intestinal microvasculature increased after formula feeding only in P9 pups. mRNA profiling revealed that regulators of arginine/nitric oxide synthesis are at higher levels in endothelial cells of the intestine of P9 than P1 pups. Importantly, arginine supplementation increased intestinal microvasculature blood flow, and prevented NEC, whereas an arginine antagonist exacerbated NEC. Our results suggest that balancing intestinal oxygen demand and supply in the premature intestine by modulating arginine/nitric oxide could be used to prevent NEC.

2019-11-05 | GSE138671 | GEO

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

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

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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.

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Formula feeding and immature gut microcirculation promote intestinal hypoxia, leading to necrotizing enterocolitis.

Project description:Major risk factors for necrotizing enterocolitis (NEC) are formula feeding and prematurity; however, their pathogenic mechanisms are unknown. Here, we found that insufficient arginine/nitric oxide synthesis limits blood flow in the intestinal microvasculature, leading to hypoxia, mucosal damage and NEC in the premature intestine after formula feeding. Formula feeding led to increased intestinal hypoxia in pups at postnatal day (P)1 and P5, but not in more mature pups at P9. Accordingly, blood flow in the intestinal microvasculature increased after formula feeding in P9 pups only. mRNA profiling revealed that regulators of arginine/nitric oxide synthesis are at higher levels in endothelial cells of the intestine in P9 than in P1 pups. Importantly, arginine supplementation increased intestinal microvasculature blood flow and prevented NEC, whereas an arginine antagonist exacerbated NEC. Our results suggest that balancing intestinal oxygen demand and supply in the premature intestine by modulating arginine/nitric oxide could be used to prevent NEC.This article has an associated First Person interview with the first author of the paper.

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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 Pigs from treatment groups TPN (n=5), and 8 h (n=5) and 24 h (n=5-6) FORM and COLOS were randomly selected for microarray analysis. Equal amounts of total distal small intestinal RNA from all pigs was 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 and eight different array control oligonucleotides (ArrayControl; Ambion, NÃ¦rum, Denmark). The immunologically relevant 60-70mer oligonucleotide probes represent interferons and interleukins (and receptors), chemokines (and receptors), acute phase proteins, apoptosis-related factors and sequences with relevance to Toll-like receptors and their intracellular signalling pathways.

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