Mechanisms by which intestinal bacteria contribute to maintenance of tolerance in food allergy

肠道细菌有助于维持食物过敏耐受性的机制

基本信息

  • 批准号:
    10411606
  • 负责人:
  • 金额:
    $ 5.23万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2020
  • 资助国家:
    美国
  • 起止时间:
    2020-08-12 至 2023-11-30
  • 项目状态:
    已结题

项目摘要

The prevalence of food allergy has experienced an unprecedented increase in Western societies, rising by as much as 20% in a recent ten-year period. We have previously described a role for mucosa- associated commensal bacteria in protection from allergic sensitization in mice. To understand how the microbiota regulates allergic disease in humans, we colonized germ free mice with human bacteria from the feces of healthy or cow’s milk allergic (CMA) infants. Our data shows that colonization with bacteria derived from healthy human infant feces is sufficient to protect mice against sensitization to the cow’s milk allergen b-lactoglobulin (BLG), whereas colonization with feces from human CMA infants fails to protect. By analyzing operational taxonomic units (OTUs) differentially abundant between our human fecal donors (4 healthy, 4 CMA) we have defined a microbial signature that distinguishes the CMA and heathy populations in both the human donors and the colonized mice, emphasizing the clinical relevance of our gnotobiotic model. RNASeq analysis of ileal intestinal epithelial cells revealed differentially expressed genes (DEGs) that distinguished healthy- and CMA-colonized mice across all donors. Correlation of ileal OTUs with DEGs in the ileum of healthy-colonized mice identified a Clostridial species, Anaerostipes caccae, that protected against an allergic response to food. Our findings demonstrate a causal role for the healthy infant microbiota in protection against food allergy and suggest that interventions that modulate bacterial communities may inform the development of novel therapeutic strategies for this disease. In this proposal we will further refine our OTU signature and examine whether the CMA infant microbiome is an atopic microbiome in Aim 1. Aim 2 will explore how healthy intestinal bacteria influence the response to food allergens by examining their impact on innate lymphoid cell function, early T/B priming and effector T cell differentiation and migration. The robust, pre-clinical gnotobiotic models we describe will provide an ideal system in which to identify key host-microbial interactions that contribute to the maintenance of tolerance to dietary antigen in food allergy.
在西方社会,食物过敏的发病率史无前例地上升

项目成果

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CATHRYN R NAGLER其他文献

CATHRYN R NAGLER的其他文献

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{{ truncateString('CATHRYN R NAGLER', 18)}}的其他基金

Mechanisms by which intestinal bacteria contribute to maintenance of tolerance in food allergy
肠道细菌有助于维持食物过敏耐受性的机制
  • 批准号:
    9884024
  • 财政年份:
    2019
  • 资助金额:
    $ 5.23万
  • 项目类别:
Mechanisms by which intestinal bacteria contribute to maintenance of tolerance in food allergy
肠道细菌有助于维持食物过敏耐受性的机制
  • 批准号:
    10305655
  • 财政年份:
    2019
  • 资助金额:
    $ 5.23万
  • 项目类别:
Mechanisms by which intestinal bacteria contribute to maintenance of tolerance in food allergy
肠道细菌有助于维持食物过敏耐受性的机制
  • 批准号:
    10517504
  • 财政年份:
    2019
  • 资助金额:
    $ 5.23万
  • 项目类别:
Protective role of intestinal microbiota in food allergy
肠道微生物群在食物过敏中的保护作用
  • 批准号:
    8985651
  • 财政年份:
    2014
  • 资助金额:
    $ 5.23万
  • 项目类别:
Protective role of intestinal microbiota in food allergy
肠道微生物群在食物过敏中的保护作用
  • 批准号:
    8787710
  • 财政年份:
    2014
  • 资助金额:
    $ 5.23万
  • 项目类别:
Regulation of Intestinal inflammation by TLR4-mediated signals
TLR4 介导的信号调节肠道炎症
  • 批准号:
    8102070
  • 财政年份:
    2010
  • 资助金额:
    $ 5.23万
  • 项目类别:
Regulation of Intestinal inflammation by TLR4-mediated signals
TLR4 介导的信号调节肠道炎症
  • 批准号:
    8017286
  • 财政年份:
    2010
  • 资助金额:
    $ 5.23万
  • 项目类别:
ALTERED RESPONSES TO FOOD PROTEINS IN ENTERIC INFECTION
肠道感染中食物蛋白质反应的改变
  • 批准号:
    7032855
  • 财政年份:
    2000
  • 资助金额:
    $ 5.23万
  • 项目类别:
Altered Responses to Food Proteins in Enteric Infections
肠道感染中食物蛋白质反应的改变
  • 批准号:
    6973978
  • 财政年份:
    2000
  • 资助金额:
    $ 5.23万
  • 项目类别:
ALTERED RESPONSES TO FOOD PROTEINS IN ENTERIC INFECTION
肠道感染中食物蛋白质反应的改变
  • 批准号:
    6711117
  • 财政年份:
    2000
  • 资助金额:
    $ 5.23万
  • 项目类别:

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