Dietary advanced glycation end-products promote food allergy by disrupting intestinal barrier and enhancing Th2 immunity

Qiaozhi Zhang, Gang Yu, Yuhao Jiang, Haining Shi, Xiaorong Yang, Zhongshan Gao, Qingqing Wang, Jinlu Sun, Chong Wang, Qianqian Li, Huatao Li and Linglin Fu ()
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Qiaozhi Zhang: Zhejiang Gongshang University
Gang Yu: Zhejiang Gongshang University
Yuhao Jiang: Zhejiang Gongshang University
Haining Shi: Harvard Medical School
Xiaorong Yang: Zhejiang Gongshang University
Zhongshan Gao: Zhejiang University
Qingqing Wang: Zhejiang University School of Medicine
Jinlu Sun: Peking Union Medical College Hospital
Chong Wang: Zhejiang Gongshang University
Qianqian Li: Zhejiang Gongshang University
Huatao Li: Zhejiang Gongshang University
Linglin Fu: Zhejiang Gongshang University

Nature Communications, 2025, vol. 16, issue 1, 1-17

Abstract: Abstract Epidemiological studies have suggested a link between the consumption of foods high in advanced glycation end-products (AGEs) and an increased risk of food allergy (FA). However, the underlying mechanisms remain largely unelucidated. In this study, we present complementary epidemiological and experimental evidence showing the pathogenic role of dietary AGEs (dAGEs) in facilitating the development of FA. We first provide a population-based cross-sectional survey supporting the association between a dietary pattern rich in AGE-laden processed foods and an increased prevalence of self-reported allergic diseases, including FA. Through multiple experimental models of FA, we demonstrate that exposure to dAGEs promotes susceptibility to allergic sensitization and amplifies Th2-biased immune response to concomitant food allergens. dAGEs possess both barrier-disruptive and Th2-adjuvant properties to induce a compromised intestinal barrier function and Th2-skewed immunity at intestinal mucosal sites. This aberrant immune response is mediated by the intricate interplay between the receptor for AGEs (RAGE) and toll-like receptor-4 (TLR4) signaling pathways. Furthermore, the Th2-stimulating effect of dAGEs involving RAGE-TLR4 crosstalk was validated in human peripheral immune cells. This study contributes to our understanding of dAGEs as a risk factor for FA and highlights the potential of dAGEs restriction as a promising preventative strategy for susceptible populations.

Date: 2025
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DOI: 10.1038/s41467-025-60235-0

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