Beyond the Gut: Necrotizing Enterocolitis as a Gut-Brain Axis Disorder of Neurodevelopment

Necrotizing enterocolitis (NEC) is a major cause of illness and death in preterm infants and is increasingly linked to long-term neurodevelopmental issues among survivors. Usually seen as a gastrointestinal disease, NEC is rarely viewed from a brain-centered perspective. In this Perspective, we suggest that NEC should be understood as a disorder of the gut-brain axis affecting neurodevelopment. We combine clinical and experimental evidence showing that intestinal inflammation, microbial imbalance, epithelial barrier failure, and systemic immune activation during NEC all contribute to the disruption of early brain development. We contend that neurodevelopmental damage is a key feature of NEC rather than just a secondary effect of prematurity. Recognizing NEC as a gut-brain axis disorder is crucial for research models, treatment approaches, and assessing long-term outcomes in affected infants.