Division of Immunology, Allergy and Rheumatology, Department of Pediatrics, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA.
J Allergy Clin Immunol. 2013 Jan;131(1):201-12. doi: 10.1016/j.jaci.2012.10.026. Epub 2012 Nov 30.
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.
共生微生物在维持口腔耐受中起着关键作用。食物过敏对肠道微生物生态的影响尚不清楚。
我们旨在确定实验性食物过敏中肠道微生物组的组成及其在疾病发病机制中的作用。
具有白细胞介素 4 受体α链（Il4raF709）功能获得性突变的食物过敏倾向小鼠和野生型（WT）对照动物接受鸡卵卵清蛋白（OVA）的口服致敏。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 16S rDNA 寡核苷酸微阵列（PhyloChip）和 16S rDNA 扩增子的大规模平行焦磷酸测序对肠道微生物群落结构进行分析。
OVA 致敏的 Il4raF709 小鼠表现出特定的微生物群特征，其特征是几个细菌科的分类群丰度的协调变化，包括 Lachnospiraceae、Lactobacillaceae、Rikenellaceae 和 Porphyromonadaceae。这种特征与类似致敏的 WT 小鼠不同，WT 小鼠没有表现出 OVA 诱导的过敏反应。用 OVA 特异性 Treg 细胞治疗 OVA 致敏的 Il4raF709 小鼠导致与过敏反应抑制一致的独特的与耐受相关的特征。过敏原致敏的 Il4raF709 小鼠的微生物组在 WT 无菌小鼠中重新组成时，可不同地促进 OVA 特异性 IgE 反应和过敏反应。
食物过敏小鼠表现出特定的肠道微生物群特征，能够传递疾病易感性，并可通过强制耐受进行重新编程。因此，疾病相关的微生物组可能在食物过敏中发挥致病作用。
