Human breast milk enhances intestinal mucosal barrier function and innate immunity in a pediatric human enteroid model

Breastfeeding has been associated with long lasting health benefits. Nutrients and bioactive components of human breast milk promote cell growth, immune development, and shield the infant gut from insults and microbial threats. The molecular and cellular events involved in these processes are ill defined. We have established human pediatric enteroids and interrogated maternal milk's impact on epithelial cell maturation and function in comparison with commercial infant formula. Colostrum applied apically to pediatric enteroid monolayers reduced ion permeability, stimulated epithelial cell differentiation and enhanced tight junction function by upregulating occludin expression. Breast milk heightened the production of antimicrobial peptidea-defensin 5 by goblet and Paneth cells, and modulated cytokine production abolishing apicalrelease of pro-inflammatory GM-CSF. These attributes were not found in commercial infantformula. Epithelial cells exposed to breast milk elevated apical and intracellular pIgR expression and enable maternal IgA translocation. Proteomic data revealed a breast milk-inducedmolecular pattern associated with tissue remodeling and homeostasis. Using a novel ex vivo pediatric enteroid model, we have identified cellular and molecular pathways involved in humanmilk-mediated improvement of human intestinal physiology and immunity.

Automated summary

Breastfeeding provides long-lasting health benefits for infants, promoting cell growth, immune development, and gut protection. Using a human pediatric enteroid model, it was found that breast milk affects epithelial cell maturation and function differently compared to commercial infant formula. This highlights the unique impact of breast milk on human intestinal physiology and immunity.