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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'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.

SUBMITTER: Noel G

PROVIDER: S-EPMC8313895 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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

Noel Gaelle G In Julie G JG Lemme-Dumit Jose M JM DeVine Lauren R LR Cole Robert N RN Guerrerio Anthony L AL Campbell James D JD Kovbasnjuk Olga O Pasetti Marcela F MF

Frontiers in cell and developmental biology 20210713

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 ...[more]

PMID: 34327199

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Project description:BackgroundThe interaction between nutrition and immunity plays a vital role in nutrient digestion, absorption, and metabolism during poultry production. Recent studies showed that the gut microbiota contributes to the development of intestinal mucosal immunity. However, the mechanisms by which gut microbes regulate this process remain unclear.MethodsWe compared the intestinal mucosal immunity and gut microbiota of Arbor Acre broilers (AA (lower mucosal immunity) and Chinese native Wuliang Mountain Black-bone chickens (WLMB) (higher mucosal immunity) using 16S rDNA sequencing, transcriptomic analysis, and immunoglobulin A (IgA) antibody repertoire sequencing. We then combined 16S rDNA sequencing with transcriptomics to identify the key microbes and found that they were positively correlated with IgA production. Next, we transplanted candidate microbes into 1-day-old broiler to explore their role in intestinal mucosal immunity. Finally, we verified the function of candidate microbial metabolites in regulating the immune function of macrophages and the intestinal-epithelial cells (IECs) using in vitro experiments.ResultsWLMB performs stronger mucosal immunity than AA, including higher IgA levels, more diverse IgA antibody repertoire, and higher bacterial affinity. Bacteroides was identified as the key microbes related to the intestinal IgA response. Bacteroides transplantation could increase IgA concentration in the duodenal contents by enhancing the expression of IgA, polymeric immunoglobin receptor (PIgR), B cell-activating factor of the TNF family (BAFF), and activation-induced cytidine deaminase (AID) in the duodenum. Additionally, Bacteroides-derived isovaleric acid promoted M2 macrophage polarization of macrophage via mTOR/PPAR-γ/STAT3 signaling pathways and regulated the immunologic function of IECs to produce cytokines, including interleukin (IL)-10, IL-4, BAFF, and transforming growth factor-beta (TGF-β), thus promoting IgA production in B cells by facilitating AID expression.ConclusionOur study revealed that Bacteroides modulate the intestinal IgA response and maintain gut health in broilers. Bacteroides may be a promising alternative as an immunomodulatory microbial agent for developing next-generation probiotics for broiler production.

Dataset Information

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

Publications

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

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