Introducing enteral feeding induces intestinal subclinical inflammation and respective chromatin changes in preterm pigs

Rhea Willems, Lukasz Krych, Verena Rybicki, Pingping Jiang, Per T Sangild, René L Shen, Kai O Hensel, Stefan Wirth, Jan Postberg, Andreas C Jenke

27 Citationer (Scopus)

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.

OriginalsprogEngelsk
TidsskriftEpigenomics
Vol/bind7
Udgave nummer4
Sider (fra-til)553-65
Antal sider13
ISSN1750-1911
DOI
StatusUdgivet - 2015

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