Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg.
Faculty of Science, Technology and Medicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg.
Nat Microbiol. 2023 Oct;8(10):1863-1879. doi: 10.1038/s41564-023-01464-1. Epub 2023 Sep 11.
Alterations in the gut microbiome, including diet-driven changes, are linked to the rising prevalence of food allergy. However, little is known about how specific gut bacteria trigger the breakdown of oral tolerance. Here we show that depriving specific-pathogen-free mice of dietary fibre leads to a gut microbiota signature with increases in the mucin-degrading bacterium Akkermansia muciniphila. This signature is associated with intestinal barrier dysfunction, increased expression of type 1 and 2 cytokines and IgE-coated commensals in the colon, which result in an exacerbated allergic reaction to food allergens, ovalbumin and peanut. To demonstrate the causal role of A. muciniphila, we employed a tractable synthetic human gut microbiota in gnotobiotic mice. The presence of A. muciniphila within the microbiota, combined with fibre deprivation, resulted in stronger anti-commensal IgE coating and innate type-2 immune responses, which worsened symptoms of food allergy. Our study provides important insights into how gut microbes can regulate immune pathways of food allergy in a diet-dependent manner.
肠道微生物组的改变，包括饮食驱动的变化，与食物过敏的发病率上升有关。然而，人们对特定的肠道细菌如何引发口服耐受的破坏知之甚少。在这里，我们表明，剥夺无特定病原体小鼠的膳食纤维会导致粘液降解菌阿克曼氏菌（Akkermansia muciniphila）增加的肠道微生物组特征。这种特征与肠道屏障功能障碍、1 型和 2 型细胞因子表达增加以及结肠中 IgE 涂层共生菌有关，导致对食物过敏原、卵清蛋白和花生的过敏反应加剧。为了证明阿克曼氏菌的因果作用，我们在无菌小鼠中使用了一种易于处理的合成人类肠道微生物组。微生物组中存在阿克曼氏菌，加上膳食纤维的缺乏，导致更强的抗共生 IgE 涂层和先天 2 型免疫反应，从而加重食物过敏的症状。我们的研究提供了重要的见解，说明肠道微生物如何以饮食依赖的方式调节食物过敏的免疫途径。
