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
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.
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
Project description:Preterm infants are highly susceptible to late-onset sepsis (LOS) and necrotizing enterocolitis (NEC) but specific biomarkers for diagnosis and effective treatment are lacking. Neutrophil extracellular traps (NETs) are related to sepsis in adults but not investigated in infant conditions. This is the first proteome study to document that circulating NETs are involved in neonatal LOS and NEC. cfDNA and NET proteins may provide new potential diagnostic markers for these diseases.
Project description:We have employed miRNA microarray expression profiling to identify miRNA differentially expressed in neonatal bowel tissues with different gastrointestinal conditions. Bowel tissues were collected from infants who underwent surgery treatment for necrotizing enterocolitis (NEC), spontaneous intestinal perforation (SIP). Infants with other non-inflammatory, congenital intestinal conditions were employed as the Surgical-Control. Differential miRNA microarray analysis was performed.
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.
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.
Project description:Necrotizing enterocolitis (NEC), a severe gut disorder in preterm infants, is difficult to predict due to poor specificity and sensitivity of clinical signs and biomarkers. Using preterm piglets as a model, we hypothesized that early development of NEC affects blood gene expression, potentially related to early systemic immune responses. In this animal model, variable severity of gut NEC lesions were detected in 5d-old piglets with limited clinical signs. NEC (n=20) and control piglets (CON, n=19) were analyzed for whole blood transcriptome, revealing 344 differentially expressed genes (DEGs) between NEC and CON piglets. Co-expression network analyses and qPCR suggested AOAH, FKBP5, PAK2 as three NEC-specific genes associated with severe gut lesions. These results suggest that whole blood gene expressions are affected in preterm piglets when clinical symptoms of NEC are minimal. Blood transcriptome may be a novel tool to identify early biomarkers of NEC.
Project description:Necrotizing enterocolitis (NEC) is the most common and lethal gastrointestinal disease affecting preterm infants. NEC develops suddenly and is characterized by gut barrier destruction, an inflammatory response, intestinal necrosis and multi-system organ failure. There is currently no method for early NEC detection, and the pathogenesis of NEC remains unclear.
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.
