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Goat's milk feeding enhances innate and adaptive immunities and alleviates allergen-induced airway inflammation in offspring mice

ABSTRACT: Goat’s milk (GM), as compared to Cow’s milk (CM), is easier for human to digest and absorb. GM feeding can improve colic, minor digestive disorders, asthma or eczema in infants. It has been demonstrated that GM have antioxidant and anti-inflammatory effects. Whether GM consumed in pregnant mothers has any immune-modulating effects on their newborns is still unclear. In this study, we used pregnant mothers and their offspring mice to verify this hypothesis. we collected feces of offspring before allergen sensitization (day 0) and two days after i.t. allergen challenge (day 16). Detection of cDNA of feces using Applied Biosystems™ Axiom™ Microbiome Array found the phyla of Bacteroidia, Clostridia, Flavobacteriia, Deferribacteres, Verrucomicrobiae and Gammaproteobacteria as well as some unclassified viruses. Comparison in ratio of Firmicutes to Bacteroidetes (F/B ratio), water-fed (W0) group had higher F/B ratio (0.79) than GM-fed (G0) (0.50) and CM-fed (C0) group (0.54) at Day 0. After HDM allergen sensitization and challenge, there was a remarkable increase of F/B ratio in water-fed mice (0.63 in WN vs. 0.84 in WA), while there was no change of F/B ratio in GM-fed (GN vs. GA) and CM-fed mice (CN vs. CA)

ORGANISM(S): Mus musculus metagenomes

PROVIDER: GSE144086 | GEO | 2020/01/23

REPOSITORIES: GEO

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Project description:Cow milk (CM) allergy is the most prevalent food allergy in young children in the US and Great Britain. Current diagnostic tests are either unreliable (IgE, skin prick test), or resource-intensive with risks (food challenges). Here we set out to determine if allergen-specific T cells in cow milk allergic (CMA) patients have a distinct quality and/or quantity that could potentially be used as a diagnostic marker. Starting from cow milk extract, we mapped T cell responses to a set of reactive epitopes that we compiled in a peptide pool. This pool induced cytokine responses in in vitro cultured cells distinguishing allergic from non-allergic subjects. Using single-cell RNA and paired TCR sequencing we detected significant changes in the transcriptional program and clonality of cow milk antigen-specific (CM+) T cells elicited by the pool in allergic vs. non-allergic subjects ex vivo. CM+ T cells from allergic subjects had increased percentages of FOXP3+ over FOXP3- cells. FOXP3+ cells are often equated with regulatory T cells (Tregs) that have suppressive activity, but CM+ FOXP3+ cells from allergic subjects showed significant expression of interferon-responsive genes and dysregulated chemokine receptor expression compared to non-allergic subjects, suggesting that these are not conventional Tregs. The CM+ FOXP3+ cells were also more clonally expanded than the FOXP3- population. We were further able to utilize surface markers (CD25, CD127, CCR7) in combination with our peptide pool stimulation to quantify these CM+ FOXP3+ cells by a simple flow cytometry assay. We show increased percentages of CM+ CD127-CD25+ cells from CMA subjects in an independent cohort, which could be used for diagnostic purposes. Looking specifically for Th2 cells normally associated with allergic diseases, we found a small population of clonally expanded CM+ cells that were significantly increased in CMA subjects and that had high expression of Th2 cytokines and pathogenic Th2/Tfh markers. Overall, these findings suggest that there are several differences in the phenotype of CM+ T cells with CM allergy and that the increase in CM+ FOXP3+ cells is a potential diagnostic marker of an allergic state. Such markers have promising applications in monitoring natural disease outgrowth and/or the efficacy of immunotherapy that will need to be validated in future studies.

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Goat's milk feeding enhances innate and adaptive immunities and alleviates allergen-induced airway inflammation in offspring mice

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