Volume 2 Supplement 1

Abstracts of the 51st Workshop for Pediatric Research

Open Access

Introduction of formula feeding induces subclinical inflammation and altered chromatin structure in the intestine of preterm pigs

  • Rhea Willems1,
  • Verena Rybicki1,
  • Pingping Jiang2,
  • Per Torp Sangild2,
  • René Liang Shen2,
  • Kai O Hensel1,
  • Stefan Wirth1,
  • Jan Postberg1 and
  • Andreas C Jenke1
Molecular and Cellular Pediatrics20152(Suppl 1):A6

https://doi.org/10.1186/2194-7791-2-S1-A6

Published: 1 July 2015

Aim

Whereas enteral nutrition has been recognized to play an important role for the development of necrotizing enterocolitis (NEC), the exact pathomechanism is still under debate [1, 2]. In this study we aimed to analyze how introduction of enteral foods affects intestinal gene regulation and chromatin structure of different inflammatory and pattern recognition genes (i.e. IL8, TLR2, TLR4, REG3A) in premature pigs before any clinical symptoms of NEC.

Methods

In total 15 preterm piglets were either provided with total parenteral nutrition (n = 5) or minimal enteral nutrition - bovine colostrum (n = 5) or preterm infant formula (n = 5). Gene expression analyses of the genes mentioned above were performed by quantitative PCR. Changes in chromatin conformation were assessed by endonuclease hypersensitivity assays. Functional studies analyzing the influence of chromatin conformation changes on the inflammatory response upon stimulation by lipopolysaccharide (LPS) were performed in CaCo-2 cells using the histone deacetylase inhibitor Trichostatin A (TSA).

Results

Enteral feeding induced a significant up-regulation of pro inflammatory genes such as IL8 and TLR 4 in the absence of any clinical symptoms of NEC. Those effects were more distinct in the formula fed subgroup compared to piglets who received colostrum. Most up-regulated genes, particularly IL8 and TLR4, were associated with endonuclease hypersensitive regions and were thus located in de-condensed, active chromatin. In consistence with this finding, TSA pretreated Caco-2 cells exhibit a significant higher IL 8 up-regulation after LPS exposure compared to controls.

Conclusion

Enteral feeding in general and formula in particular influences the regulation of key inflammatory genes and their respective epigenetic signatures in the premature gut. This might contribute to the increased susceptibility to NEC in premature infants. In consequence, more studies are urgently required to optimize enteral nutrition in preterm infants.

Authors’ Affiliations

(1)
Department of Neonatology, HELIOS Children´s Hospital, Centre for Biomedical Education and Research (ZBAF), Witten/Herdecke University
(2)
Comparative Pediatrics and Nutrition, Dept. Clinical Veterinary and Animal Science, and Copenhagen University Hospital (Rigshospitalet), University of Copenhagen

References

  1. Morgan J, Young L, McGuire W: Delayed introduction of progressive enteral feeds to prevent necrotising enterocolitis in very low birth weight infants. Cochrane Database Syst Rev 2013, 5: CD001970.PubMedGoogle Scholar
  2. Nanthakumar NN, Fusunyan RD, Sanderson I, Walker WA: Inflammation in the developing human intestine: A possible pathophysiologic contribution to necrotizing enterocolitis. Proc Natl Acad Sci USA 2000,97(11):6043–6048. 10.1073/pnas.97.11.6043PubMed CentralPubMedView ArticleGoogle Scholar

Copyright

© Willems et al. 2015

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.