A role for early oral exposure to house dust mite allergens through breastmilk in IgE-mediated food allergy susceptibility

Abstract Background Successful prevention of food allergy requires the identification of the factors adversely affecting the capacity to develop oral tolerance to food antigen in early life. Objectives To determine whether oral exposure to Der p through breastmilk affects gut mucosal immunity with long-term effects on IgE-mediated food allergy susceptibility. Methods Gut immunity was explored in 2 weeks-old mice breastfed by mothers exposed to Der p, protease-inactivated Der p (iDer p) or to PBS during lactation. We further analysed oral tolerance to a bystander food allergen, Ovalbumin (OVA). In a proof of concept study, Der p 1 and OVA levels were determined in 100 human breastmilk samples and the association with prevalence of IgE- mediated egg allergy at one year assessed. Results Increased permeability, IL-33 levels, ILC2 activation and Th2 cell differentiation were found in gut mucosa of mice nursed by mothers exposed to Der p as compared to PBS. This pro-Th2 gut mucosal environment inhibited the induction of antigen-specific FoxP3 regulatory T cells and the prevention of food allergy by OVA exposure through breastmilk. In contrast, iDer p had no effect on offspring gut mucosal immunity. Based on the presence of Der p and/or OVA in human breastmilk, we identified groups of lactating mothers, which mirror the ones found in mice to be responsible for different egg allergy risk. Conclusion This study highlights an unpredicted potential risk factor for the development of food allergy, i.e. Der p in breastmilk, which disrupts gut immune homeostasis and prevents oral tolerance induction to bystander food antigen through their protease activity.