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痰和口腔微生物群与轻度哮喘的特应性、免疫学和临床特征的不同关联。

Distinct associations of sputum and oral microbiota with atopic, immunologic, and clinical features in mild asthma.

机构信息

Department of Medicine, Division of Gastroenterology, University of California, San Francisco, Calif.

Department of Microbiology & Immunology and Sandler Asthma Basic Research Center, San Francisco, Calif.

出版信息

J Allergy Clin Immunol. 2020 Nov;146(5):1016-1026. doi: 10.1016/j.jaci.2020.03.028. Epub 2020 Apr 13.

Abstract

BACKGROUND

Whether microbiome characteristics of induced sputum or oral samples demonstrate unique relationships to features of atopy or mild asthma in adults is unknown.

OBJECTIVE

We sought to determine sputum and oral microbiota relationships to clinical or immunologic features in mild atopic asthma and the impact on the microbiota of inhaled corticosteroid (ICS) treatment administered to ICS-naive subjects with asthma.

METHODS

Bacterial microbiota profiles were analyzed in induced sputum and oral wash samples from 32 subjects with mild atopic asthma before and after inhaled fluticasone treatment, 18 atopic subjects without asthma, and 16 nonatopic healthy subjects in a multicenter study (NCT01537133). Associations with clinical and immunologic features were examined, including markers of atopy, type 2 inflammation, immune cell populations, and cytokines.

RESULTS

Sputum bacterial burden inversely associated with bronchial expression of type 2 (T2)-related genes. Differences in specific sputum microbiota also associated with T2-low asthma phenotype, a subgroup of whom displayed elevations in lung inflammatory mediators and reduced sputum bacterial diversity. Differences in specific oral microbiota were more reflective of atopic status. After ICS treatment of patients with asthma, the compositional structure of sputum microbiota showed greater deviation from baseline in ICS nonresponders than in ICS responders.

CONCLUSIONS

Novel associations of sputum and oral microbiota to immunologic features were observed in this cohort of subjects with or without ICS-naive mild asthma. These findings confirm and extend our previous report of reduced bronchial bacterial burden and compositional complexity in subjects with T2-high asthma, with additional identification of a T2-low subgroup with a distinct microbiota-immunologic relationship.

摘要

背景

诱导痰或口腔样本的微生物组特征是否与成年人特应性或轻度哮喘的特征存在独特的关系尚不清楚。

目的

我们旨在确定痰和口腔微生物组与轻度特应性哮喘的临床或免疫学特征之间的关系,以及吸入性皮质类固醇(ICS)治疗对哮喘患者中 ICS 治疗的影响。

方法

在一项多中心研究(NCT01537133)中,分析了 32 例轻度特应性哮喘患者吸入氟替卡松治疗前后的诱导痰和口腔洗液的细菌微生物组谱,其中 18 例为特应性无哮喘受试者,16 例为非特应性健康受试者。检查了与临床和免疫学特征的关联,包括特应性、2 型炎症、免疫细胞群和细胞因子的标志物。

结果

痰细菌负荷与气道 2 型(T2)相关基因的表达呈负相关。特定痰微生物组的差异也与 T2-低哮喘表型相关,其中一部分人显示肺炎症介质升高和痰细菌多样性降低。特定口腔微生物组的差异更能反映特应性状态。在哮喘患者接受 ICS 治疗后,ICS 无应答者的痰微生物组组成结构较基线偏离更大,而 ICS 应答者则偏离较小。

结论

在该队列中,无论有无 ICS 初治轻度哮喘,都观察到痰和口腔微生物组与免疫学特征的新关联。这些发现证实并扩展了我们之前关于 T2 高哮喘患者支气管细菌负荷和组成复杂性降低的报告,此外还确定了一个具有独特微生物-免疫关系的 T2 低亚组。

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