Human breast milk exosomes attenuate intestinal damage

Abstract

Background: Human breast milk (HBM), which contains an abundant supply of exosomes, is known to prevent necrotizing enterocolitis (NEC). Preterm infants are commonly given pasteurized donor milk when HBM is unavailable. However, pasteurization can disrupt its components. This study investigates the effects of both raw and pasteurized HBM-derived exosomes on intestinal inflammation. Methods: HBM exosomes were isolated and characterized by positive CD63 and negative calnexin markers from western blot, nanoparticle tracking analysis and transmission electron microscopy. Mouse intestine organoids were established and treated with exosomes from raw or pasteurized HBM in healthy and injury conditions. Following ethical approval (#44032), mice pups were randomly assigned to (1) breastfed control; (2) NEC; (3) NEC receiving raw HBM exosomes; (4) NEC receiving pasteurized HBM exosomes. NEC was induced by hypoxia, gavage feeding and lipopolysaccharide (LPS). Ileum was evaluated. Data were analyzed using one-way ANOVA with Bonferroni post-test. Results: Both raw and pasteurized HBM exosomes decreased inflammation in hypoxia and LPS-treated organoids compared to control. In vivo, NEC-induced mucosal injury, inflammation and mucous production were improved by raw and pasteurized HBM-derived exosomes. Conclusions: Exosomes derived from raw and pasteurized HBM equally reduced intestinal damage. Exosome administration in clinical practice requires further investigation.