Human Breast Milk Enhances Intestinal Mucosal Barrier Function and Innate Immunity in a Healthy Pediatric Human Enteroid Model

Gaelle Noel; Julie G In; Jose M Lemme-Dumit; Lauren R DeVine; Robert N Cole; Anthony L Guerrerio; James D Campbell; Olga Kovbasnjuk; Marcela F Pasetti

doi:10.3389/fcell.2021.685171

Human Breast Milk Enhances Intestinal Mucosal Barrier Function and Innate Immunity in a Healthy Pediatric Human Enteroid Model

Front Cell Dev Biol. 2021 Jul 13:9:685171. doi: 10.3389/fcell.2021.685171. eCollection 2021.

Authors

Affiliations

¹ Department of Pediatrics, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, United States.
² Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of New Mexico Health Science Center, Albuquerque, NM, United States.
³ Department of Medicine, Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
⁴ Department of Biological Chemistry, Johns Hopkins Mass Spectrometry and Proteomics Facility, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
⁵ Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology and Nutrition, Johns Hopkins University School of Medicine, Baltimore, MD, United States.

Abstract

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. Breast milk heightened the production of antimicrobial peptide α-defensin 5 by goblet and Paneth cells, and modulated cytokine production, which abolished apical release of pro-inflammatory GM-CSF. These attributes were not found in commercial infant formula. Epithelial cells exposed to breast milk elevated apical and intracellular pIgR and enabled maternal IgA translocation. Proteomic data revealed a breast milk-induced molecular pattern associated with tissue remodeling and homeostasis. Using a novel ex vivo pediatric enteroid model, we have identified distinct cellular and molecular events involved in human milk-mediated improvement of human intestinal physiology and immunity.

Keywords: breastmilk; enteroid; epithelial barrier; innate immunity; occludin; pIgR polymeric immunoglobulin receptor; pediatric (infant).

Abstract

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