How dietary advanced glycation end products could facilitate the occurrence of food allergy

Background: Food allergy (FA) is one of the most common chronic conditions in children with an increasing prevalence facilitated by the exposure to environmental factors in predisposed individuals. It has been hypothesized that the increased consumption of ultra -processed foods, containing high levels of dietary advanced glycation end products (AGEs), could facilitate the occurrence of FA. Objective: We sought to provide preclinical and clinical evidence on the potential role of AGEs in facilitating the occurrence of FA. Methods: Human enterocytes, human small intestine organ culture, and PBMCs from children at risk for allergy were used to investigate the direct effect of AGEs on gut barrier, inflammation, TH2 cytokine response, and mitochondrial function. Intake of the 3 most common glycation products in Western diet foods, N epsilon-(carboxymethyl) lysine, N epsilon-(1- carboxyethyl) lysin, and Nd-(5-hydro-5- methyl-4-imidazolone2-yl)-ornithine (MG -H1), and the accumulation of AGEs in the skin were comparatively investigated in children with FA and in age -matched healthy controls. Results: Human enterocytes exposed to AGEs showed alteration in gut barrier, AGE receptor expression, reactive oxygen species production, and autophagy, with increased transepithelial passage of food antigens. Small intestine organ cultures exposed to AGEs showed an increase of CD251 cells and proliferating crypt enterocytes. PBMCs exposed to AGEs showed alteration in proliferation rate, AGE receptor activation, release of inflammatory and TH2 cytokines, and mitochondrial metabolism. Significant higher dietary AGE intake and skin accumulation were observed children with FA (n = 42) compared with age -matched healthy controls (n = 66). Conclusions: These data, supporting a potential role for dietary AGEs in facilitating the occurrence of FA, suggest the importance of limiting exposure to AGEs children as a potential preventive strategy against this common condition. (J Allergy Clin Immunol 2024;153:742-58.)