Effects of Allergen-Specific and Non-Specific AGEs on the Allergenicity of Ovalbumin in a Mouse Model of Food Allergy.

ABSTRACT

SCOPE Epidemiologic studies suggest a link between the incidence of food allergy and the consumption of dietary advanced glycation end-products (AGEs). However, the pathogenic role of dietary AGEs in food allergy is largely unknown. This study aims to investigate the effect of allergen-specific and non-specific AGEs on the allergenic manifestation of ovalbumin (OVA), a typical food allergen in vivo. METHODS AND RESULTS: OVA is glycated by methylglyoxal to prepare allergen-specific AGEs (i.e., OVA-AGE), and a standard AIN-93G diet is heated to obtain allergen-non-specific AGEs. A BALB/c mouse model orally sensitizes to OVA with different forms of AGEs is established and the outcomes are measured as clinical signs, specific antibodies, type-2/type-2 cytokines, immune cell subpopulations, intestinal barrier function, and gut microbiota (GM) composition. The OVA-AGE which has a lower immunoglobulin E (IgE)-binding level in vitro does not reduce the allergenicity of OVA but promotes a stronger T helper 2 cells (Th2)-response than native OVA in vivo. Both forms of AGEs up-regulate the expression of splenic RAGE and aggravate the destruction of gut barrier and GM dysbiosis, especially when exposes to non-relevant AGEs. CONCLUSION: This study highlights the role of dietary AGEs in food allergy and helps to understand the biological consequences of immune-toxic compounds in modern diet.