Dietary Fiber and Bacterial SCFA Enhance Oral Tolerance and Protect against Food Allergy through Diverse Cellular Pathways

Dietary Fiber and Bacterial SCFA Enhance Oral Tolerance and Protect against Food Allergy through Diverse Cellular Pathways
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DOI:
10.1016/j.celrep.2016.05.047
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发表时间:
2016-06-21
期刊:
影响因子:
8.8
通讯作者:
Mackay, Charles R.
Mackay, Charles R.
中科院分区:
生物学1区
文献类型:
--
作者:
Tan, Jian;McKenzie, Craig;Mackay, Charles R.

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近几十年来,西方国家食物过敏的发病率急剧增加。对食物抗原的耐受依赖于粘膜 CD103(+) 树突状细胞 (DC),其促进调节性 T (Treg) 细胞的分化。我们发现,高纤维喂养可以提高小鼠的口腔耐受性并防止食物过敏。高纤维喂养重塑了肠道微生物生态并增加了短链脂肪酸(SCFA)的释放,特别是乙酸盐和丁酸盐。高纤维喂养通过增强 CD103(+) DC 中的视网膜脱氢酶活性来增强口服耐受性并防止食物过敏。这种保护作用取决于饮食中的维生素 A。这种喂养方案还促进了 IgA 的产生并增强了滤泡辅助 T 和粘膜生发中心的反应。缺乏 SCFA 受体 GPR43 或 GPR109A 的小鼠表现出食物过敏加剧和 CD103(+) DC 减少。因此,包括纤维和维生素 A 在内的膳食元素可调节胃肠道中的许多保护途径,这是免疫对食物抗原无反应所必需的。
The incidence of food allergies in western countries has increased dramatically in recent decades. Tolerance to food antigens relies on mucosal CD103(+) dendritic cells (DCs), which promote differentiation of regulatory T (Treg) cells. We show that high-fiber feeding in mice improvedoral tolerance and protected from food allergy. High-fiber feeding reshaped gut microbial ecology and increased the release of short-chain fatty acids (SCFAs), particularly acetate and butyrate. High-fiber feeding enhanced oral tolerance and protected against food allergy by enhancing retinal dehydrogenase activity in CD103(+) DC. This protection depended on vitamin A in the diet. This feeding regimen also boosted IgA production and enhanced T follicular helper and mucosal germinal center responses. Mice lacking GPR43 or GPR109A, receptors for SCFAs, showed exacerbated food allergy and fewer CD103(+) DCs. Dietary elements, including fiber and vitamin A, therefore regulate numerous protective pathways in the gastrointestinal tract, necessary for immune non-responsiveness to food antigens.