Despite the potential of oral immunotherapy against food allergy, adverse reactions and loss of desensitization hinder its clinical uptake. Dysbiosis of the gut microbiota is implicated in the increasing prevalence of food allergy, which will need to be regulated to enable for an effective oral immunotherapy against food allergy. Here we report an inulin gel formulated with an allergen that normalizes the dysregulated ileal microbiota and metabolites in allergic mice, establishes allergen-specific oral tolerance and achieves robust oral immunotherapy efficacy with sustained unresponsiveness in food allergy models. These positive outcomes are associated with enhanced allergen uptake by antigen-sampling dendritic cells in the small intestine, suppressed pathogenic type 2 immune responses, increased interferon-γ⁺ and interleukin-10⁺ regulatory T cell populations, and restored ileal abundances of Eggerthellaceae and Enterorhabdus in allergic mice. Overall, our findings underscore the therapeutic potential of the engineered allergen gel as a suitable microbiome-modulating platform for food allergy and other allergic diseases.

尽管口服免疫疗法具有对抗食物过敏的潜力，但不良反应和脱敏作用的丧失阻碍了其临床应用。肠道微生物群的失调与食物过敏患病率的增加有关，需要对其进行调节，以实现针对食物过敏的有效口服免疫疗法。在这里，我们报告了一种用过敏原配制的菊粉凝胶，可以使过敏小鼠失调的回肠微生物群和代谢物正常化，建立过敏原特异性的口服耐受性，并在食物过敏模型中持续无反应的情况下实现强大的口服免疫治疗功效。这些积极结果与小肠中抗原采样树突状细胞增强的过敏原摄取、抑制致病性 2 型免疫反应、增加干扰素 γ ⁺ 和白细胞介素 10 ⁺ 调节相关。 T 细胞群，并恢复了过敏小鼠回肠中埃格氏菌科和肠杆菌属的丰度。总体而言，我们的研究结果强调了工程过敏原凝胶作为食物过敏和其他过敏性疾病的合适微生物组调节平台的治疗潜力。