Features of the bronchial bacterial microbiome associated with atopy, asthma and responsiveness to inhaled corticosteroid treatment.. Bronchial microbiome in asthma, atopy, and health.

Background: Compositional differences in bronchial bacterial microbiota have been associated with asthma, but it remains unclear whether the findings are attributable to asthma, to aeroallergen sensitization or to inhaled corticosteroid treatment.Objectives: To compare the bronchial bacterial microbiota in adults with steroid-naive atopic asthma (AA), with atopy but no asthma (ANA), and non-atopic healthy subjects (HC), and determine relationships of bronchial microbiota to phenotypic features of asthma.Methods: Bacterial communities in protected bronchial brushings from 42 AA, 21 ANA, and 21 HC subjects were profiled by 16S rRNA gene sequencing. Bacterial composition and community-level functions inferred from sequence profiles were analyzed for between-group differences. Associations with clinical and inflammatory variables were examined, including markers of type 2-related inflammation and change in airway hyper-responsiveness following six weeks of fluticasone treatment. Results: The bronchial microbiome differed significantly among the three groups. Asthmatic subjects were uniquely enriched in members of the Haemophilus, Neisseria, Fusobacterium, Porphyromonas and Sphingomonodaceae, and depleted in members of the Mogibacteriaceae and Lactobacillales. Asthma-associated differences in predicted bacterial functions included involvement of amino acid and short-chain fatty acid metabolism pathways. Subjects with type 2-high asthma harbored significantly lower bronchial bacterial burden. Distinct changes in specific microbiota members were seen following fluticasone treatment. Steroid-responsiveness was linked to differences in baseline compositional and functional features of the bacterial microbiome. Conclusion: Even in mild steroid-naive asthma subjects, differences in the bronchial microbiome are associated with immunologic and clinical features of the disease. The specific differences identified suggest possible microbiome targets for future approaches to asthma treatment or prevention.

背景：支气管细菌微生物群的组成差异与哮喘存在关联，但目前仍不清楚该研究结果是归因于哮喘本身、气源性致敏原致敏，还是吸入性糖皮质激素（inhaled corticosteroid）治疗。
目的：对比未使用过糖皮质激素的特应性哮喘（steroid-naive atopic asthma, AA）患者、伴特应性但无哮喘（atopy but no asthma, ANA）人群以及非特应性健康受试者（non-atopic healthy subjects, HC）的支气管细菌微生物群，并明确支气管微生物群与哮喘表型特征的关联。
方法：本研究采用16S rRNA基因测序（16S rRNA gene sequencing），对42例AA患者、21例ANA人群及21例HC受试者的保护性支气管刷检标本中的细菌群落进行谱型分析；基于测序谱型推断的细菌组成及群落水平功能，分析组间差异，并探究其与临床及炎症变量的关联，包括2型相关炎症标志物以及氟替卡松（fluticasone）治疗6周后气道高反应性的变化情况。
结果：三组受试者的支气管微生物组存在显著差异。哮喘患者的嗜血杆菌属（Haemophilus）、奈瑟菌属（Neisseria）、梭杆菌属（Fusobacterium）、卟啉单胞菌属（Porphyromonas）及鞘氨醇单胞菌科（Sphingomonodaceae）成员显著富集，而莫氏菌科（Mogibacteriaceae）及乳杆菌目（Lactobacillales）成员则显著减少。哮喘相关的预测细菌功能差异涉及氨基酸代谢及短链脂肪酸代谢通路。2型炎症高的哮喘患者支气管细菌负荷显著更低。氟替卡松治疗后，特定微生物群成员出现了显著变化。糖皮质激素应答性与细菌微生物组的基线组成及功能特征差异相关。
结论：即便是轻度未使用过糖皮质激素的哮喘患者，其支气管微生物组的差异仍与疾病的免疫及临床特征相关。本研究鉴定出的特定差异提示，未来哮喘治疗或预防手段可将微生物群作为潜在靶点。