Abstract

Necrotizing Enterocolitis (NEC) is the most common and often fatal intestinal disorder in preterm infants. Breast‐fed infants are at much lower risk to develop NEC than formula‐fed infants. We hypothesize that Human Milk Oligosaccharides (HMO), complex glycans highly abundant in breast milk but not in formula, contribute to the protective effects of breast‐feeding. In an established NEC model neonatal Sprague‐Dawley rats were either left with the dam to serve as breast‐fed control or orally gavaged with formula without and with HMO. All pups were exposed to hypoxia thrice a day, sacrificed on day 4, and their intestines analyzed for macroscopic and microscopic signs of NEC. Histology sections of the terminal ileum were scored blindly from 0 (healthy) to 4 (complete destruction). The average pathology score in breast‐fed pups was 0.15+/−0.34. It was significantly increased to 1.98+/−1.11 in pups receiving formula without HMO (P<0.001). Addition of HMO reduced the pathology score to 0.44+/−0.30, which was significantly lower than in the group receiving formula without HMO (P<0.001) but not different from the breast‐fed control. Galactooligosaccharides (GOS), currently added to most infant formula to mimic HMO, had no effect. We are now identifying individual HMO responsible for the beneficial effects and aim to understand the underlying molecular mechanisms. (Supported by NIH K99/R00DK078668 to LB)

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