Rhea Willems1, Lukasz Krych2, Verena Rybicki1, Pingping Jiang3, Per T Sangild3, René L Shen3, Kai O Hensel1, Stefan Wirth1, Jan Postberg1, Andreas C Jenke1. 1. 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. 2. Department of Food Science, Faculty of Science, University of Copenhagen, Frederiksberg, Denmark. 3. Comparative Pediatrics & Nutrition, Department Clinical Veterinary & Animal Science, Copenhagen University Hospital (Rigshospitalet), University of Copenhagen, Denmark.
Abstract
AIM: To analyze how enteral food introduction affects intestinal gene regulation and chromatin structure in preterm pigs. MATERIALS & 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). CONCLUSION: 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.
AIM: To analyze how enteral food introduction affects intestinal gene regulation and chromatin structure in preterm pigs. MATERIALS & 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). CONCLUSION: 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.
Entities:
Keywords:
DNA methylation; chromatin; enteral nutrition; necrotizing enterocolitis; premature infants
Authors: Carl Frederik Hansen; Thomas Thymann; Anders Daniel Andersen; Jens Juul Holst; Bolette Hartmann; Linda Hilsted; Louise Langhorn; Jacob Jelsing; Per Torp Sangild Journal: Am J Physiol Gastrointest Liver Physiol Date: 2016-01-28 Impact factor: 4.052
Authors: Sonja Zamrik; Federica Giachero; Michael Heldmann; Kai O Hensel; Stefan Wirth; Andreas C Jenke Journal: Biomed Res Int Date: 2018-11-13 Impact factor: 3.411