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Published on: October 31, 2025
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Subclinical necrotizing enterocolitis-induced systemic immune suppression in neonatal preterm pigs
Shuqiang Ren1,2, Xiaoyu Pan1, Yan Hui3
1Section for Comparative Pediatrics and Nutrition, Department of Veterinary and Animal Sciences, University of Copenhagen, Denmark.
Summary
Necrotizing enterocolitis (NEC) in preterm infants can lead to systemic immune suppression, increasing sepsis risk. This study in preterm pigs shows even mild NEC lesions impair immune responses, explaining higher infection susceptibility.
Area of Science:
- Neonatal immunology
- Gastrointestinal pathology
- Infectious disease mechanisms
Background:
- Preterm infants face high risks of necrotizing enterocolitis (NEC) and sepsis.
- NEC is suspected to predispose infants to sepsis, but underlying mechanisms remain unclear.
Purpose of the Study:
- To investigate the immune status in preterm pigs with subclinical NEC-like lesions.
- To determine if NEC severity influences systemic immune responses.
Main Methods:
- Preterm pigs were used to model NEC development and assessed on days 5 and 9.
- Immune status was evaluated via blood analysis (T-cell subsets, neutrophil function, transcriptomics) and gut histology/cytokine analysis.
- Animals were categorized by NEC lesion severity: healthy, mild, or severe.
Main Results:
- NEC incidence was high (61-62%) on both days, with lower severity by day 9, suggesting mucosal repair.
- NEC lesions correlated with decreased goblet cells and increased immune cell infiltration in the gut.
- On day 9, NEC pigs (especially severe cases) exhibited systemic immune suppression, including elevated Tregs, impaired neutrophil phagocytosis, and reduced innate/Th1 gene expression.
Conclusions:
- Subclinical NEC lesions, even mild ones, induce systemic immune suppression in preterm pigs.
- This immune suppression may explain the increased susceptibility to secondary infections and sepsis in preterm infants with NEC.

