# Selenium deficiency is functionally linked with the molecular etiopathogenesis of necrotizing enterocolitis (NEC)

## TL;DR

This study finds that selenium deficiency is linked to the development of necrotizing enterocolitis in premature infants, involving genes related to hypoxia, inflammation, and cell death.

## Contribution

The study provides novel molecular evidence linking selenium deficiency to the pathogenesis of necrotizing enterocolitis in premature infants.

## Key findings

- Selenium-related genes (e.g., GPX1, GPX4) were downregulated in NEC-affected neonates.
- Genes involved in hypoxia, apoptosis, and inflammation were significantly upregulated in NEC cases.
- Pathways related to oxidative stress, selenium metabolism, and programmed cell death were dysregulated in NEC.

## Abstract

Necrotizing enterocolitis (NEC) is a severe and often catastrophic gastrointestinal emergency that predominantly affects neonates, especially those born prematurely, and is associated with high rates of morbidity and mortality. Despite its significant clinical impact, the precise etiology and molecular pathogenesis of NEC remain incompletely understood. In this study, we conducted global transcriptomic profiling using high-throughput RNA sequencing in 11 premature neonates diagnosed with NEC, following rigorous inclusion and exclusion criteria. Compared to healthy controls, we identified 1,204 differentially expressed genes (DEGs), including 636 upregulated and 568 downregulated transcripts. Notably, genes involved in hypoxia-induced apoptosis (e.g., HIF1 AAS3, HIF1 AAS1), the caspase cascade (BCL2, BCL6, CASP5, CASP7), and inflammation (IL1RAP, IL6ST, TNFAIP3, TNFRSF10 A, TLR6, TLR10) were significantly upregulated. In contrast, IL18, a key modulator of inflammatory responses, was downregulated. Interestingly, several genes encoding selenoproteins (GPX1, GPX4, SELENON, SELENOM, SELENOF, SELENOW, SELENOT) were also downregulated, suggesting molecular evidence of selenium deficiency. Gene ontology and pathway enrichment analyses revealed widespread dysregulation in pathways related to hypoxia response, systemic inflammation, coagulation, antimicrobial defense, mitochondrial function, autophagy, selenium metabolism, and apoptosis. Collectively, our findings provide novel insights into the molecular underpinnings of NEC in premature infants and suggest that systemic hypoxia, oxidative stress, selenium deficiency, and programmed cell death contribute significantly to its pathogenesis.

The online version contains supplementary material available at 10.1007/s10142-025-01628-8.