Intestinal DNA methylome of preterm pigs
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PROVIDER: PRJNA423044 | ENA |
REPOSITORIES: ENA
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Project description:DNA methylation plays important roles in normal development as well as sensing environmental exposures, thereby regulating transcription that is associated with cellular functions. Shortened gestational age and unexpected exposure to milk and microbes at the wrong time may affect intestinal development and health via DNA methylation. The present studies aimed to characterize the intestinal DNA methylomes of preterm neonates at birth and during postnatal development, in order to understand the cellular basis of the immature intestine and its interaction with early nutrition.
2018-12-18 | GSE108284 | GEO
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
Project description:Intestinal microbiota colonization is important for intestinal development and health of preterm infants, especially those with extremely low birth weight. Recent studies indicated for a dynamic crosstalk between that gut microbiota and DNA methylome of host intestinal cells. Thereby, we sought to determine the epigenomic and metagenomic consequences of suppression of microbiota colonization in the intestine of preterm neonates to gain insights into biological pathways that shape the interface between the gut microbiota and the preterm intestinal cells. We examined 14 preterm piglets by comparing the conventional preterm neonates with those ones treated with oral antibiotics for genome wide DNA methylation and 16S rDNA microbiome. Our results demonstrated an extensive genome-wide DNA methylation changes in response to the suppression of intestinal microbe colonization, especially genes involved in neonatal immune response signaling and glycol-metabolism pathways were identified. Our study highlights several key genes that might predispose preterm neonates to NEC risk due to their key roles involved in the immune-metabolic networks. Our study not only provided rich omic-data to interpret molecular program in relation with microbiota-associated methylome-proteome network changes, but also confer clinical usage of key gene markers for potential early diagnostics of NEC of preterm neonates.
2017-10-12 | GSE88697 | GEO
Project description:We hypothesized that the immature pig intestine would be highly sensitive to gene methylation changes in the immediate prenatal and neonatal periods. We performed a Reduced Representation Bisulfite Sequencing (RRBS) to assess the DNA methylation differences occurring during the last 10 days prenatally (PN, 0d-term vs. 0d-preterm), neonatally after 4 days (NN, 4d-preterm vs. 0d-preterm) and after NEC development (4d-preterm-NEC vs. 4d-preterm) in pigs (each group n=2-3). Differentially methylated gene regions (DMRs) between the groups were identified, subjected to KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis and selected genes were chosen for further validation of gene expression levels by RT-PCR (n= 6 for each group). Consistent with the need to increase expression of many intestinal genes in the perinatal period, methylation levels of most genes decreased during the prenatal and neonatal periods. We identified four intestinal genes (CYP2W1, GPR146, TOP1MT, CEND1), related to intestinal metabolism, that were significantly hyper-methylated in their promoter CGIs, and transcriptionally down-regulated in the 4 d-old preterm pigs. This down-regulation of intestinal metabolism may predispose to intestinal dysfunction and NEC. The first enteral feeds and bacterial colonization are critical factors for NEC sensitivity and it remains to be investigated whether these factors affect intestinal gene methylation and thereby predispose to, or prevent from, disease more long term.
2014-12-31 | GSE53747 | GEO
Project description:Caesarean-delivered preterm pigs were fed 3 d of parenteral nutrition followed by 2 d of enteral formula feeding. Antibiotics (n=11) or control saline (n=13) were given twice daily from birth to tissue collection at d 5. NEC-lesions and intestinal structure, function, microbiology and immunity markers were recorded. We used Affymetrix microarrays to investigate gene expression in intestinal tissues of preterm piglets treated with antibiotics or control saline. Twenty-four preterm piglets were delivered by caesarean section on day 105 of gestation from two healthy sows. All piglets were initially provided with parenteral nutrition via a vascular catheter, combined with small amounts of minimal enteral nutrition. On day three, all parenteral nutrition was stopped and total enteral nutrition was given through an oro-gastric feeding tube. Piglets were allocated into controls ( n=13) and an intervention group receiving oral and systemic broad-spectrum antibiotics ( n=11). To assure high systemic and intra luminal MIC values antibiotics were given both orally and intramuscularly. All antibiotics were given directly after feeding with an oral bolus and control pigs were given corresponding amounts of saline. On day five, all piglets were euthanized, and small intestinal tissue collected.
2013-08-21 | E-GEOD-48125 | biostudies-arrayexpress
Project description:Caesarean-delivered preterm pigs were fed 3 d of parenteral nutrition followed by 2 d of enteral formula feeding. Antibiotics (n=11) or control saline (n=13) were given twice daily from birth to tissue collection at d 5. NEC-lesions and intestinal structure, function, microbiology and immunity markers were recorded. We used Affymetrix microarrays to investigate gene expression in intestinal tissues of preterm piglets treated with antibiotics or control saline.
2013-08-21 | GSE48125 | GEO
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
2010-03-01 | GSE13515 | GEO
Project description:Background: Neonatal infection and sepsis are common for preterm infants due to their immature immune system. Early diagnosis is important for effective treatment but few early markers of systemic and neuro-inflammatory responses in neonates are known. We hypothesized that systemic infection with Gram-positive Staphylococcus epidermidis (SE) induces acute changes to proteins in plasma and cerebrospinal fluid (CSF), potentially affecting the immature brain of preterm neonates. Methods: Using preterm pigs as model for preterm infants, plasma and CSF samples were collected up to 24 h after SE infection and investigated by untargeted mass spectrometry (MS)-based proteomics. Selected differential proteins were further studied in vitro assays. Results: The clinical signs of sepsis and neuroinflammation in SE-infected piglets were associated with changes in multiple CSF and plasma proteins. Eight plasma proteins, including APOA4, haptoglobin, MBL1, vWF, LBP and sCD14, were affected already 6 h after infection. Likewise, acute phase reactants, including complement components, showed a time-dependent activation pattern after infection. Feeding bovine colostrum reduced the sepsis-related change in clinical parameters as well as plasma proteins. Neuroinflammation-related neuropeptide Y (NPY), IL-18 and MMP-14 showed distinct changes in the CSF and several brain regions (prefrontal cortex, PVWM, hippocampus) 24 h after infection. These changes were verified in TLR2 agonist-challenged primary microglia cells, where exogenous NPY suppressed the inflammatory response. Conclusion: Systemic infection with Gram-positive SE induces inflammation with rapid proteome changes in plasma and CSF in preterm newborn pigs. The observed early markers of sepsis and neuroinflammation in preterm pigs may serve as novel biomarkers for sepsis in preterm infants.
2020-05-26 | PXD016013 | Pride
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, Nærum, 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.
2010-05-07 | E-GEOD-13516 | biostudies-arrayexpress
Project description:Microbial Biomarkers of Intestinal Barrier Maturation in Preterm Infants
| PRJEB29365 | ENA