@article{e47b6c2f63a2459c9f37d04530ec0633,
title = "Human Breast Milk Enhances Intestinal Mucosal Barrier Function and Innate Immunity in a Healthy Pediatric Human Enteroid Model",
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{\textquoteright}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)",
author = "Gaelle Noel and In, {Julie G.} and Lemme-Dumit, {Jose M.} and DeVine, {Lauren R.} and Cole, {Robert N.} and Guerrerio, {Anthony L.} and Campbell, {James D.} and Olga Kovbasnjuk and Pasetti, {Marcela F.}",
note = "Funding Information: This work was supported by a Grand Challenge Exploration Award (Bill and Melinda Gates Foundation) OPP 1118529 and in part, by NIH grants R01AI117734 (to MFP), P01 AI125181 (to MFP and OK), K01 DK106323 (to JGI), and University of New Mexico Department of Internal Medicine start-up funds (to JGI and OK). The authors acknowledge the Integrated Physiology and Imaging Cores of the Hopkins Digestive Disease Basic and Translational Research Core Center (P30 DK089502) and the Johns Hopkins Mass Spectrometry and Proteomics Core. Funding Information: Funding. This work was supported by a Grand Challenge Exploration Award (Bill and Melinda Gates Foundation) OPP 1118529 and in part, by NIH grants R01AI117734 (to MFP), P01 AI125181 (to MFP and OK), K01 DK106323 (to JGI), and University of New Mexico Department of Internal Medicine start-up funds (to JGI and OK). The authors acknowledge the Integrated Physiology and Imaging Cores of the Hopkins Digestive Disease Basic and Translational Research Core Center (P30 DK089502) and the Johns Hopkins Mass Spectrometry and Proteomics Core. Publisher Copyright: {\textcopyright} Copyright {\textcopyright} 2021 Noel, In, Lemme-Dumit, DeVine, Cole, Guerrerio, Campbell, Kovbasnjuk and Pasetti.",
year = "2021",
month = jul,
day = "13",
doi = "10.3389/fcell.2021.685171",
language = "English (US)",
volume = "9",
journal = "Frontiers in Cell and Developmental Biology",
issn = "2296-634X",
publisher = "Frontiers Media S. A.",
}