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

Background: Food allergy (FA) is one of the most common chronic conditions in the pediatric age with an increasing prevalence under the pressure of 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 food allergy.Objective: Here we 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 peripheral mononuclear blood cells (PBMCs) from children at risk for allergy were used to investigate the direct effect of AGEs on gut barrier, inflammation, Th2 cytokines response and mitochondrial function. The intake of the three most commonly glycation products in Western diet-foods N? -(carboxymethyl) lysine (CML), N? -(1-carboxyethyl) lysine (CEL), and N? -(5-hydro-5- methyl-4-imidazolon-2-yl)-ornithine (MG-H1), and the skin AGEs accumulation were comparatively investigated in children with FA and in age-matched healthy controls.Results: Human enterocytes exposed to AGEs showed alteration in gut barrier, AGEs receptor expression, reactive oxygen species production and autophagy, with increased transepithelial passage of food antigens. Small intestine organ culture exposed to AGEs showed an increase of CD25+ cells and proliferating crypt enterocytes. PBMCs exposed to AGEs showed alteration in proliferation rate, AGEs receptor activation, release of inflammatory and Th2 cytokines, and mitochondrial metabolism. Significant higher dietary AGEs intake and skin accumulation were observed in FA children (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 the AGEs exposure in the pediatric age as potential preventive strategy against this common condition.