Neonatal necrotizing enterocolitis-associated DNA methylation signatures in the colon are evident in stool samples of affected individuals

Epigenomics. 2021 Jun;13(11):829-844. doi: 10.2217/epi-2021-0078. Epub 2021 Apr 27.

Abstract

Aim: Neonatal necrotizing enterocolitis (NEC) is a deadly and unpredictable gastrointestinal disease, for which no biomarker exists. We aimed to describe the methylation patterns in stool and colon from infants with NEC. Methods: We performed a high-resolution genome-wide epigenomic analysis using solution-phase hybridization and next-generation sequencing of bisulfite-converted DNA. Results: Our data reveal significant genomic hypermethylation in NEC tissues compared with non-NEC controls. These changes were more pronounced in regions outside CpG islands and gene regulatory elements, suggesting that NEC-specific hypermethylation is not a nonspecific global phenomenon. Conclusions: This study provides evidence of a methylomic signature associated with NEC that is detectable noninvasively and provides a new opportunity for the development of a novel diagnostic method for NEC.

Keywords: DNA methylation; biomarker; colon; epigenetics; intestine; methylome; necrotizing enterocolitis; neonatal; prematurity; stool.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers*
  • CpG Islands
  • DNA Methylation*
  • Disease Susceptibility*
  • Enterocolitis, Necrotizing / diagnosis
  • Enterocolitis, Necrotizing / etiology*
  • Enterocolitis, Necrotizing / metabolism
  • Epigenesis, Genetic
  • Epigenomics / methods
  • Feces
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Genome-Wide Association Study
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Sequence Analysis, DNA
  • Signal Transduction

Substances

  • Biomarkers