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. 2025 Mar;17(4):235-245.
doi: 10.1080/17501911.2025.2459552. Epub 2025 Feb 2.

Detection of an intestinal cell DNA methylation signature in blood samples from neonates with necrotizing enterocolitis

Lauren Frazer  1 , Tianjiao Chu  2   3 , Patricia Shaw  3 , Camille Boufford  4 , Lucas Tavares Naief  3 , Michaela Ednie  3 , Laken Ritzert  3 , Caitlin P Green  5 , Misty Good  1 , David Peters  2   3   4
Affiliations

Detection of an intestinal cell DNA methylation signature in blood samples from neonates with necrotizing enterocolitis

Lauren Frazer et al. Epigenomics. 2025 Mar.

Abstract

Background: Necrotizing enterocolitis (NEC) is an often fatal intestinal injury that primarily affects preterm infants for which screening tools are lacking. We performed a pilot analysis of DNA methylation in peripheral blood samples from preterm infants with and without NEC to identify potential NEC biomarkers.

Methods: Peripheral blood samples were collected from infants at NEC diagnosis (n = 15) or from preterm controls (n = 13). Targeted genome-wide analysis was performed to identify DNA methylation differences between cases and controls.

Results: Broad differences between NEC cases and controls were identified in distinct genomic elements. Differences between surgical NEC cases and controls were frequently associated with inflammation. Deconvolution analysis to identify cell type-specific DNA signatures revealed increases in ileal, vascular endothelial, and cardiomyocyte cell type proportions and decreases in colonic and neuronal cell type proportions in blood from NEC cases relative to controls.

Conclusions: We identified marked differences in DNA methylation of peripheral blood samples from preterm infants with and without NEC. Increased ileal cell-specific methylation signatures in the blood of infants with NEC relative to controls, with a marked increase seen in surgical cases, provides rationale for further analysis of intestinal DNA methylation signatures as biomarkers of NEC.

Keywords: DNA methylation; biomarker; blood; epigenetics; necrotizing enterocolitis; neonatal; prematurity.

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