A microbiota signature associated with experimental food allergy promotes allergic sensitization and anaphylaxis.

A microbiota signature associated with experimental food allergy promotes allergic sensitization and anaphylaxis.
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DOI:
10.1016/j.jaci.2012.10.026
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发表时间:
2013-01
影响因子:
14.2
通讯作者:
Chatila, Talal A.
Chatila, Talal A.
中科院分区:
医学1区
文献类型:
--
作者:
Noval Rivas, Magali;Burton, Oliver T.;Wise, Petra;Zhang, Yu-qian;Hobson, Suejy A.;Lloret, Maria Garcia;Chehoud, Christel;Kuczynski, Justin;DeSantis, Todd;Warrington, Janet;Hyde, Embriette R.;Petrosino, Joseph F.;Gerber, Georg K.;Bry, Lynn;Oettgen, Hans C.;Mazmanian, Sarkis K.;Chatila, Talal A.

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共生菌群在维持口服耐受性中起着关键作用。食物过敏对肠道微生物生态的影响仍然未知。我们试图建立实验性食物过敏中肠道微生物群的组成及其在疾病发病机制中的作用。对IL-4受体α链中具有功能获得性突变的食物过敏易感小鼠(Il 4 raF 709)和野生型(WT)对照动物进行鸡蛋卵清蛋白(OVA)口服致敏。通过使用过敏原特异性调节性T(Treg)细胞实现强制耐受。通过使用高密度16 S rDNA寡核苷酸微阵列(PhyloChip)和16 S rDNA扩增子的大规模平行焦磷酸测序来进行肠道微生物群的群落结构分析。OVA致敏的Il 4 raF 709小鼠表现出特定的微生物群特征,其特征在于几个细菌家族的分类群丰度的协调变化,包括毛螺菌科、乳杆菌科、Rikenellaceae和紫单胞菌科。类似致敏的WT小鼠不具有该特征,其未表现出OVA诱导的过敏反应。用OVA特异性Treg细胞处理OVA致敏的Il 4 raF 709小鼠导致与过敏反应的抑制一致的明显的耐受性相关的特征。当在WT无菌小鼠中重建时,过敏原致敏的Il 4 raF 709小鼠的微生物群差异性地促进OVA特异性IgE应答和过敏反应。食物过敏的小鼠表现出特定的肠道微生物群特征,能够传播疾病易感性,并通过强制耐受进行重编程。因此,疾病相关的微生物群可能在食物过敏中起致病作用。
Commensal microbiota play a critical role in maintaining oral tolerance. The effect of food allergy on the gut microbial ecology remains unknown. We sought to establish the composition of the gut microbiota in experimental food allergy and its role in disease pathogenesis. Food allergy–prone mice with a gain-of-function mutation in the IL-4 receptor α chain (Il4raF709) and wild-type (WT) control animals were subjected to oral sensitization with chicken egg ovalbumin (OVA). Enforced tolerance was achieved by using allergen-specific regulatory T (Treg) cells. Community structure analysis of gut microbiota was performed by using a high-density 16S rDNA oligonucleotide microarrays (PhyloChip) and massively parallel pyrosequencing of 16S rDNA amplicons. OVA-sensitized Il4raF709 mice exhibited a specific microbiota signature characterized by coordinate changes in the abundance of taxa of several bacterial families, including the Lachnospiraceae, Lactobacillaceae, Rikenellaceae, and Porphyromonadaceae. This signature was not shared by similarly sensitized WT mice, which did not exhibit an OVA-induced allergic response. Treatment of OVA-sensitized Il4raF709 mice with OVA-specific Treg cells led to a distinct tolerance-associated signature coincident with the suppression of the allergic response. The microbiota of allergen-sensitized Il4raF709 mice differentially promoted OVA-specific IgE responses and anaphylaxis when reconstituted in WT germ-free mice. Mice with food allergy exhibit a specific gut microbiota signature capable of transmitting disease susceptibility and subject to reprogramming by enforced tolerance. Disease-associated microbiota may thus play a pathogenic role in food allergy.
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