The Role of the Microbiome in the Development/Prevention of Food Allergies

描述（由申请人提供）：在过去的几十年里，西方文化中食物过敏的流行率稳步上升。虽然过敏发生率增加的原因可能是多因素的，但越来越多的数据支持这一假设，即胃肠道微生物群的组成可能是对其他无害食物蛋白质产生过敏反应的一个促成因素。我们最近开发了一种对鸡卵清蛋白（OVA）食物过敏的小鼠模型，其响应于微生物群扰动而发展。Ag特异性T细胞应答将通过OVA特异性初始DO11.10 CD 4 T细胞的过继转移来追踪。我们的假设是，胃肠道微生物群的紊乱，包括酵母菌的暂时或长期生长，通过破坏调节网络和/或增强粘膜Th 2应答的启动，促进Th 2应答对高剂量食物过敏原暴露的启动。因此，针对微生物群的策略（益生菌和益生元）有可能恢复有缺陷的调节反应和/或防止过敏原引发。我们的目的是：1）确定口服OVA后，微生物群破坏小鼠肠系膜淋巴结和固有层中的细胞、体液和细胞因子反应; 2）确定乳酸杆菌益生菌、益生元（scFOS）或两者的组合对细胞的影响，口服OVA后，微生物群破坏小鼠肠系膜淋巴结和固有层中的体液和细胞因子应答; 3）确定丁酸盐和全反式维甲酸在调节从未处理和微生物菌群破坏的小鼠的MLN和LP分离的CD 103-和CD 103+树突状细胞的活性方面的关系。 公共卫生相关性 许多流行病学研究表明，本地微生物群的破坏（抗生素，饮食，疾病或其他环境因素）是粘膜炎症性疾病（包括食物过敏）发展的致病因素。该提案的数据将增加我们对连接土著微生物群和食物过敏的机制的理解，包括益生菌治疗食物过敏的机制。

DESCRIPTION (provided by applicant): The prevalence of food allergies in Western cultures has steadily increased in the last several decades. While the cause of the increased incidence of allergies is likely to be multifactoral, a growing body of data supports the hypothesis that the composition of the gastrointestinal tract microbiota can be a contributing factor in the generation of allergic responses to otherwise innocuous food proteins. We have recently developed a mouse model of food allergy to chicken ovalbumin (OVA), which develops in response to microbiota perturbation. Ag-specific T cell responses will be tracked through the adoptive transfer of OVA-specific naive DO11.10 CD4 T-cells. Our hypothesis is that disturbances of the gastrointestinal microbiota, including the temporary or long-term outgrowth of yeast, promote the priming of a Th2 response to high dose food allergen exposure by disrupting regulatory networks and/or augmenting priming of mucosal Th2 responses. Therefore, strategies aimed at the microbiota (probiotics & prebiotcs) have the potential to restore defective regulatory responses and/or prevent allergen priming. Our aims are 1) to determine the cellular, humoral and cytokine responses in the mesenteric lymph nodes and lamina propria of microbiota-disrupted mice following oral delivery of OVA; 2) to determine the effect of a Lactobacillus probiotic, a prebiotic (scFOS) or the combination of the two on the cellular, humoral and cytokine responses in the mesenteric lymph nodes and lamina propria of microbiota-disrupted mice following oral delivery of OVA; 3) to determine the relationship between butyrate and all-trans retinoic acid on regulating the activity of CD103- and CD103+ dendritic cells isolated from the MLN and LP of untreated and microbiota-disrupted mice. Public Health Relevance Numerous epidemiologic studies have implicated disruptions of the indigenous microbiota (by antibiotics, diet, disease, or other environmental factors) as a causative factor in the development of mucosal inflammatory disorders, including food allergies. The data from this proposal will increase our understanding of the mechanisms connecting the indigenous microbiota and food allergies, including the mechanisms of probiosis to treat food allergies.