title: Introducing enteral feeding induces intestinal subclinical inflammation and respective chromatin changes in preterm pigs.
abstract: OBJECTIVE
  To analyze how enteral food introduction affects intestinal gene regulation and chromatin structure in preterm pigs.
  
  
  METHODS
  Preterm pigs were fed parenteral nutrition plus/minus slowly increasing volumes of enteral nutrition. Intestinal gene-expression and chromatin structure were analyzed 5 days after birth.
  
  
  RESULTS
  Enteral feeding led to differential upregulation of inflammatory and pattern recognition receptor genes, including IL8 (median: 5.8, 95% CI: 3.9-7.8 for formula; median: 2.2, 95% CI: 1.3-3.3 for colostrum) and TLR4 (median: 3.7, 95% CI: 2.6-4.8 for formula; no significant differences for colostrum) with corresponding decondensed chromatin configurations. On histology this correlated with mild mucosal lesions, particularly in formula-fed pigs. In CaCo-2 cells, histone hyperacetylation led to a marked increase in TLR4 mRNA and increased IL8 expression upon stimulation with lipopolysaccharide (median: 7.0; interquartile range: 5.63-8.85) compared with naive cells (median 4.2; interquartile range: 2.45-6.33; p = 0.03).
  
  
  CONCLUSIONS
  Enteral feeding, particular with formula, induces subclinical inflammation in the premature intestine and more open chromatin structure in key inflammatory genes. This may increase the susceptibility for necrotizing enterocolitis.
authors.affiliation: Department of Paediatrics, HELIOS Medical Centre Wuppertal, Centre for Clinical & Translational Research (CCTR), Faculty of Health, Centre for Biomedical Education & Research (ZBAF), Witten/Herdecke University, Heusnerstr. 40,42283 Wuppertal, Germany.
authors.forename: Rhea
authors.initials: R
authors.lastname: Willems
authors.affiliation: Department of Food Science, Faculty of Science, University of Copenhagen, Frederiksberg, Denmark.
authors.forename: Lukasz
authors.initials: L
authors.lastname: Krych
authors.affiliation: Department of Paediatrics, HELIOS Medical Centre Wuppertal, Centre for Clinical & Translational Research (CCTR), Faculty of Health, Centre for Biomedical Education & Research (ZBAF), Witten/Herdecke University, Heusnerstr. 40,42283 Wuppertal, Germany.
authors.forename: Verena
authors.initials: V
authors.lastname: Rybicki
authors.affiliation: Comparative Pediatrics & Nutrition, Department Clinical Veterinary & Animal Science, Copenhagen University Hospital (Rigshospitalet), University of Copenhagen, Denmark.
authors.forename: Pingping
authors.initials: P
authors.lastname: Jiang
authors.affiliation: Comparative Pediatrics & Nutrition, Department Clinical Veterinary & Animal Science, Copenhagen University Hospital (Rigshospitalet), University of Copenhagen, Denmark.
authors.forename: Per T
authors.initials: PT
authors.lastname: Sangild
authors.affiliation: Comparative Pediatrics & Nutrition, Department Clinical Veterinary & Animal Science, Copenhagen University Hospital (Rigshospitalet), University of Copenhagen, Denmark.
authors.forename: René L
authors.initials: RL
authors.lastname: Shen
authors.affiliation: Department of Paediatrics, HELIOS Medical Centre Wuppertal, Centre for Clinical & Translational Research (CCTR), Faculty of Health, Centre for Biomedical Education & Research (ZBAF), Witten/Herdecke University, Heusnerstr. 40,42283 Wuppertal, Germany.
authors.forename: Kai O
authors.initials: KO
authors.lastname: Hensel
authors.affiliation: Department of Paediatrics, HELIOS Medical Centre Wuppertal, Centre for Clinical & Translational Research (CCTR), Faculty of Health, Centre for Biomedical Education & Research (ZBAF), Witten/Herdecke University, Heusnerstr. 40,42283 Wuppertal, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Wirth
authors.affiliation: Department of Paediatrics, HELIOS Medical Centre Wuppertal, Centre for Clinical & Translational Research (CCTR), Faculty of Health, Centre for Biomedical Education & Research (ZBAF), Witten/Herdecke University, Heusnerstr. 40,42283 Wuppertal, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Postberg
authors.affiliation: Department of Paediatrics, HELIOS Medical Centre Wuppertal, Centre for Clinical & Translational Research (CCTR), Faculty of Health, Centre for Biomedical Education & Research (ZBAF), Witten/Herdecke University, Heusnerstr. 40,42283 Wuppertal, Germany.
authors.forename: Andreas C
authors.initials: AC
authors.lastname: Jenke
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D018938:Caco-2 Cells; D002843:Chromatin / Q000235:genetics*; D004750:Enteral Nutrition / Q000009:adverse effects*; D020345:Enterocolitis, Necrotizing / Q000209:etiology / Q000235:genetics* / Q000628:therapy / Q000662:veterinary; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D013552:Swine; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism
chemical_list: D002843:Chromatin; D016209:Interleukin-8; D051197:Toll-Like Receptor 4
keywords: DNA methylation; chromatin; enteral nutrition; necrotizing enterocolitis; premature infants