Regulation of oral antigen delivery early in life: Implications for oral tolerance and food allergy

Abstract

The increasing incidence of food allergy remains a significant public health concern. Food allergy is partially due to a lack, or loss of tolerance to food allergens. Clinical outcomes surrounding early life practices, such as breastfeeding, antibiotic use and food allergen exposure, indicate the first year of life in children represents a unique time for shaping the immune system to reduce allergic outcomes. Animal models have identified distinctive aspects of when and where dietary antigens are delivered within the intestinal tract to promote oral tolerance prior to weaning. Additionally, animal models have identified contributions from maternal proteins from breast milk and bacterial products from the gut microbiota in regulating dietary antigen exposure and promoting oral tolerance, thus connecting decades of clinical observations on the benefits of breastfeeding, early food allergen introduction and antibiotic avoidance in the first year of life in reducing allergic outcomes. Here, we discuss how exposure to gut luminal antigens, including food allergens, is regulated in early life to generate protective tolerance and the implications of this process for preventing and treating food allergies.

Figure 1:

Oral antigens are encountered through distinct routes throughout life. How these delivery pathways are regulated and the outcomes following antigen delivery are unique to each phase of life.

Figure 2:

Multiple factors contribute to establishing oral tolerance during early life. Absence of any one of these factors increases the risk of food sensitization and food allergies later in life.