House Dust Mediates Gut Microbiome Lactobacillus johnsonii Enrichment and Immune Defense Against Airway Allergens [Set1]. dust metagenome

Exposure to dogs in early infancy has been shown to reduce the risk of childhood allergic disease development and dog-ownership is associated with a distinct house dust microbial exposure. Here we demonstrate, using murine models, that exposure of mice to dog-associated house dust protects against ovalbumin or cockroach allergen mediated airway pathology. Protected animals exhibited significant reductions in the total number of airway T cells, down-regulation of Th2-related airway responses as well as mucin secretion. Following house dust exposure, the cecal microbiome of protected animals was extensively restructured with significant enrichment of, amongst others, Lactobacillus johnsonii. Supplementation of wild type animals with L. johnsonii protected them against both airway allergen challenge or infection with respiratory syncytial virus. L. johnsonii mediated protection was associated with significant reductions in the total number and proportion of activated CD11c+/CD11b+ and CD11c+/CD8+ cells, as well as significantly reduced airway Th2 cytokine expression. Our results reveal that exposure to dog-associated household dust results in protection against airway allergen challenge and a distinct GI microbiome composition. Moreover the study identifies L. johnsonii as a pivotal species within the gastrointestinal tract capable of influencing adaptive immunity at remote mucosal surfaces in a manner that is protective against a variety of respiratory insults. Overall design: The G2 PhyloChip microarray platform (commercially available from Second Genome, Inc.) was used to profile cecal gut bacteria from 29 mice: 7 controls, 5 gavaged with dust from homes with pets, 5 gavaged with dust from homes with no pets, 4 CRA-challenged, 4 gavaged with L. johnsonii, and 4 gavaged with L. johnsonii prior to CRA challenge. The PhyloChip was also used to profile 1 house dust sample collected from a home with dogs

已有研究表明，婴儿早期接触犬只可降低儿童过敏性疾病的发病风险，而饲养犬只与独特的室内灰尘微生物暴露特征相关。本研究借助小鼠模型证实，让小鼠接触犬只相关室内灰尘，可抵御卵清蛋白或蟑螂变应原介导的气道病变。经保护的小鼠模型可见气道T细胞总数显著减少，辅助性T细胞2（Th2）相关气道应答以及黏液分泌均出现下调。接触室内灰尘后，受保护小鼠的盲肠微生物组发生广泛重构，其中约氏乳杆菌（Lactobacillus johnsonii）在内的多种菌群显著富集。给野生型小鼠灌服约氏乳杆菌，可使其免受气道变应原刺激以及呼吸道合胞病毒（respiratory syncytial virus）感染。约氏乳杆菌介导的保护作用，与活化的CD11c+/CD11b+及CD11c+/CD8+细胞的总数和占比显著降低相关，同时气道Th2细胞因子的表达水平也显著下调。本研究结果显示，接触犬只相关家居灰尘可抵御气道变应原刺激，并塑造独特的胃肠道微生物组组成。此外，本研究证实约氏乳杆菌是胃肠道内的关键菌群物种，可通过调控远端黏膜表面的适应性免疫，抵御多种呼吸道损伤。实验设计方案：本研究采用G2 PhyloChip微阵列平台（可从Second Genome, Inc.公司商业获取），对29只小鼠的盲肠肠道菌群进行谱分析：其中7只为对照组，5只灌喂了养宠家庭的室内灰尘样本，5只灌喂了无宠家庭的室内灰尘样本，4只为CRA刺激组，4只灌喂了约氏乳杆菌，另有4只在接受CRA刺激前先灌喂约氏乳杆菌。此外，本研究还利用该平台对1份采自养犬家庭的室内灰尘样本进行了谱分析。