Author: Diego Javier, Class of 2026

Figure 1. X-Ray of a newborn with highlight regions displaying areas affected by NEC

Necrotizing enterocolitis (NEC) is an intestinal disease that affects around 10% of premature infants in the United States, resulting in either infant mortality or long-term developmental problems such as learning disabilities and behavioral problems in babies that do survive. While it is known that severe NEC can damage the brain and impair development, there are gaps in knowledge about whether mild NEC can trigger neuroinflammation. To address this lack of understanding, Cuileen Sha and researchers in the Wollmuth Hsieh Lab at Stony Brook University created a graded NEC mouse model using the reagent dextran sodium sulfate (DSS). This model permitted the mimicry of NEC at various degrees of severity, allowing the team to investigate if mild gut inflammation can cause changes in the brain.

To test their hypothesis, newborn mice were first separated from their mothers and fed formula containing varying concentrations of DSS for three days. During this period, the researchers monitored the weight, activity, and overall health of the mice. After the three days had elapsed, tissue was collected from the intestine, liver, blood, and brain areas. Intestinal tissue was examined for damage and cell growth, while liver and blood cells were examined for inflammatory molecules. Neurons and microglia (immune cells in the brain) in the CA1 hippocampal region, an area of the brain essential for learning and memory, were examined for signs of neuroinflammation and cellular activation.. 

The results showed a clear dependency on DSS. Higher levels of DSS caused significant effects, such as more severe intestinal injury and faster weight loss. Even at low DSS levels, there was reduced cell growth in the intestines. In addition to cell growth, the concentration of inflammatory molecules in the liver and blood increased accordingly with DSS dosage. Interestingly, even in the brains of mice with mild NEC, there were signs of immune activation. As a result of this, microglia became more active and changed shape, while neurons remained largely unaffected. 

This study displays that even mild NEC can trigger brain inflammation, providing evidence for how early gut problems can affect later neurodevelopment. The graded NEC model provides a controlled way to study the “gut-brain axis,” offering a platform to test treatments that can both manage intestinal disease and protect the brain. 

Future research can explore many different directions by studying long-term learning and behavior through identifying harmful inflammatory molecules or exploring ways to prevent or reduce NEC-related brain changes. The Wollmuth Hsieh lab highlights that even mild gut inflammation can deeply affect newborns, emphasizing the need to understand and address early intestinal injury. 

Work’s Cited:

[1] Sha, C., Van Brunt, T., Kudria, J., Schmidt, D., Yurovsky, A., Bandovic, J., Giarrizzo, M., Lin, J., Tsirka, S. A., Bialkowska, A. B., Wollmuth, L. P., Speer, E. M., & Hsieh, H. (2025). A graded neonatal mouse model of necrotizing enterocolitis demonstrates that mild enterocolitis is sufficient to activate microglia and increase cerebral cytokine expression. PloS one, 20(5), e0323626. https://doi.org/10.1371/journal.pone.0323626 

[2] Image retrieved from: https://www.ncbi.nlm.nih.gov/books/NBK513357/