The rise of food allergy: Environmental factors and emerging treatments

Abstract

Food allergy has rapidly increased in prevalence, suggesting an important role for environmental factors in disease susceptibility. The immune response of food allergy is characterized by IgE production, and new findings from mouse and human studies indicate an important role of the cytokine IL-9, which is derived from both T cells and mast cells, in disease manifestations. Emerging evidence suggests that route of exposure to food, particularly peanut, is important. Exposure through the skin promotes sensitization while early exposure through the gastrointestinal tract promotes tolerance. Evidence from mouse studies indicate a role of the microbiome in development of food allergy, which is supported by correlative human studies showing a dysbiosis in food allergy. There is no approved treatment for food allergy, but emerging therapies are focused on allergen immunotherapy to provide desensitization, while pre-clinical studies are focused on using adjuvants or novel delivery approaches to improve efficacy and safety of immunotherapy.

Keywords: Anaphylaxis; Diet; Immunotherapy; Mast cells; Microbiota; Tregs.

Fig. 1

Allergen exposure through the skin in the presence of skin damage, filaggrin mutation or bacterial toxins (SEB) promotes sensitization. Depending on the nature of the allergen and adjuvant, epithelial cells produce cytokines that instruct dendritic cells on the skin. They transport the antigen to the skin-draining lymph nodes, where Th2 and T follicular helper (Tfh) cells are generated and promote IgE class-switching. Antigen exposure by oral route leads to tolerance. CX₃CR1 + macrophages sample antigen from the lumen and transfer it to CD103 + DCs that transport the antigen to the mesenteric lymph nodes and promote the induction of Tregs. Oral tolerance can prevent the development of sensitization through the skin.

Fig. 2

Microbiota and diet influence the development of allergy and tolerance. Microbial diversity suppresses IgE class-switching, which occurs within the Peyer's patch. Strains of bacteria including Clostridia have been shown to suppress allergy, and to enhance the generation of Tregs and improve epithelial barrier function. There is also evidence that microbial composition can promote food allergy, suggesting the role of pro-allergic bacteria. Nutrients including vitamin D, aryl hydrocarbon receptor (AHR) ligands, polyunsaturated fatty acids (PUFA) and oligosaccharides can also suppress food allergy through enhancement of regulatory responses.