Diet-dependent changes in the intestinal DNA methylome after introduction of enteral feeding in preterm pigs

Epigenomics. 2018 Apr 1;10(4):395-408. doi: 10.2217/epi-2017-0122. Epub 2018 Mar 28.


Aim: To examine how enteral feeding affects the intestinal epigenome and gene expression just after preterm birth.

Materials & methods: Intestinal tissue from preterm pigs, modeling preterm infants, was collected at birth and 5 days after gradual introduction of infant formula or bovine colostrum. The intestinal tissue was analyzed by reduced representation bisulfite sequencing and real-time qPCR.

Results: Relative to colostrum, formula increased bacterial epithelial adherence and lipopolysaccharide binding protein (LBP) expression, which was regulated by promoter methylation. Diet-dependent changes in DNA methylation and/or mRNA expression were related to innate immune response, hypoxia, angiogenesis and epithelial-mesenchymal transition pathways (e.g., TTC38, IL8, C3, HIF1A and VEGFR1).

Conclusion: Epigenetic changes may mediate important effects of the first feeding on intestinal development in preterm neonates.

Keywords: DNA methylation; epigenetic gene regulation; immunity; microbiota; nutrition; preterm birth.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-Phase Proteins / biosynthesis
  • Acute-Phase Proteins / genetics
  • Animals
  • Carrier Proteins / biosynthesis
  • Carrier Proteins / genetics
  • Colostrum
  • DNA Methylation*
  • Diet*
  • Enteral Nutrition
  • Immunity, Innate / genetics
  • Infant Formula
  • Intestines*
  • Membrane Glycoproteins / biosynthesis
  • Membrane Glycoproteins / genetics
  • Promoter Regions, Genetic
  • Signal Transduction
  • Swine
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism


  • Acute-Phase Proteins
  • Carrier Proteins
  • Membrane Glycoproteins
  • Vascular Endothelial Growth Factor A
  • lipopolysaccharide-binding protein