Necrotizing enterocolitis (NEC) is a severe gastrointestinal disease in preterm infants, often leading to brain injury. The microbiota-gut-brain axis (MGBA) plays a key role, with short-chain fatty acids (SCFAs) emerging as potential therapeutic agents. This study explores the impact of SCFAs, particularly acetate, in mitigating NEC-related brain injury. A NEC rat model was established via overfeeding, hypoxia, and asphyxia. Intestinal injury, SCFA levels, systemic inflammation, and neuroinflammation were assessed through histology, gas chromatography-mass spectrometry, ELISA, and Western blotting. Cognitive function was evaluated using the Morris water maze test. NEC rats exhibited significantly lower levels of intestinal SCFAs, particularly acetate, compared to control rats. These reductions were accompanied by systemic inflammation, neuroinflammation and cognitive deficits. Supplementation with sodium acetate mitigated both intestinal and neuroinflammatory responses and improved cognitive function. Acetate depletion contributes to NEC-associated brain injury, and early acetate supplementation may offer a promising therapeutic strategy to mitigate intestinal damage, neuroinflammation, and cognitive impairment.
Hou et al. (2026) studied this question.