Zhang Qiaozhi, Yu Gang, Jiang Yuhao, Shi Haining, Yang Xiaorong, Gao Zhongshan, Wang Qingqing, Sun Jinlu, Wang Chong, Li Qianqian, Li Huatao, Fu Linglin
School of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, 310018, PR China.
Mucosal Immunology and Biology Research Center, Harvard Medical School, Boston, MA, 02129, USA.
Nat Commun. 2025 May 28;16(1):4960. doi: 10.1038/s41467-025-60235-0.
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.
流行病学研究表明，食用富含晚期糖基化终产物（AGEs）的食物与食物过敏（FA）风险增加之间存在联系。然而，其潜在机制在很大程度上仍未阐明。在本研究中，我们提供了补充性的流行病学和实验证据，表明膳食AGEs（dAGEs）在促进FA发展中具有致病作用。我们首先进行了一项基于人群的横断面调查，支持富含AGEs的加工食品的饮食模式与自我报告的过敏性疾病（包括FA）患病率增加之间的关联。通过多种FA实验模型，我们证明暴露于dAGEs会增加过敏性致敏的易感性，并放大对伴随食物过敏原的Th2偏向性免疫反应。dAGEs具有破坏屏障和Th2佐剂特性，可导致肠道屏障功能受损和肠道黏膜部位Th2偏向性免疫。这种异常免疫反应是由AGEs受体（RAGE）和Toll样受体4（TLR4）信号通路之间的复杂相互作用介导的。此外，dAGEs涉及RAGE-TLR4串扰的Th2刺激作用在人外周免疫细胞中得到了验证。本研究有助于我们将dAGEs理解为FA的一个风险因素，并强调限制dAGEs作为易感人群一种有前景的预防策略的潜力。
