Human Breast Milk Enhances Intestinal Mucosal Barrier Function and Innate Immunity in a Healthy Pediatric Human Enteroid Model
In, Julie G
Lemme-Dumit, Jose M
DeVine, Lauren R
Cole, Robert N
Guerrerio, Anthony L
Campbell, James D
Pasetti, Marcela F
JournalFrontiers in Cell and Developmental Biology
PublisherFrontiers Media S.A.
MetadataShow full item record
AbstractBreastfeeding 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.
Rights/TermsCopyright © 2021 Noel, In, Lemme-Dumit, DeVine, Cole, Guerrerio, Campbell, Kovbasnjuk and Pasetti.
pIgR polymeric immunoglobulin receptor
Identifier to cite or link to this itemhttp://hdl.handle.net/10713/16292
- Epithelial and Neutrophil Interactions and Coordinated Response to Shigella in a Human Intestinal Enteroid-Neutrophil Coculture Model.
- Authors: Lemme-Dumit JM, Doucet M, Zachos NC, Pasetti MF
- Issue date: 2022 Jun 28
- Co-Culture System of Human Enteroids/Colonoids with Innate Immune Cells.
- Authors: Staab JF, Lemme-Dumit JM, Latanich R, Pasetti MF, Zachos NC
- Issue date: 2020 Dec
- Secretory antibodies in breast milk promote long-term intestinal homeostasis by regulating the gut microbiota and host gene expression.
- Authors: Rogier EW, Frantz AL, Bruno ME, Wedlund L, Cohen DA, Stromberg AJ, Kaetzel CS
- Issue date: 2014 Feb 25
- Innate Immunity and Breast Milk.
- Authors: Cacho NT, Lawrence RM
- Issue date: 2017
- Enhancing responsiveness of human jejunal enteroids to host and microbial stimuli.
- Authors: Ruan W, Engevik MA, Chang-Graham AL, Danhof HA, Goodwin A, Engevik KA, Shi Z, Hall A, Rienzi SCD, Venable S, Britton RA, Hyser J, Versalovic J
- Issue date: 2020 Aug