{"title":"Distinct Airway Microbiome and Metabolite Profiles in Eosinophilic and Neutrophilic Asthma.","authors":"Shuang Liu, Zhiwei Lin, Jiayong Zhou, Xiaojing Yang, Liuyong You, Qianyue Yang, Tianyang Li, Zhaoming Hu, Xuyan Zhan, Yueting Jiang, Baoqing Sun","doi":"10.2147/JAA.S521800","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Asthma is a chronic, heterogeneous disease driven by inflammatory phenotypes, primarily eosinophilic asthma (EA) and neutrophilic asthma (NEA). While allergen triggers are well-known, the role of the airway microbiome and metabolites in asthma exacerbations remains poorly understood.</p><p><strong>Methods: </strong>We recruited 64 participants (24 EA, 20 NEA, 20 healthy controls [HC]) for the discovery cohort, with validation in an external cohort (10 EA, 8 NEA, 8 HC). Induced sputum samples were analyzed using 16S rRNA sequencing to profile bacterial composition and non-targeted metabolomics to assess airway metabolites. Random forest models identified diagnostic markers, validated in the external cohort.</p><p><strong>Results: </strong>Significant shifts in airway microbiota were observed, particularly between NEA and HC, and between EA and NEA. Four bacterial general-<i>Stenotrophomonas</i>, <i>Streptococcus</i>, <i>Achromobacter</i>, and <i>Neisseria</i>-were consistently identified across groups. <i>Veillonella</i> was more abundant in NEA vs HC, while <i>Achromobacter</i> was enriched in NEA vs EA, indicating distinct microbial signatures. Metabolomic profiling revealed distinct pathways: pyrimidine metabolism (EA vs HC), tryptophan metabolism (NEA vs HC), and arachidonic acid metabolism (EA vs NEA). Microbial-metabolite correlations indicated microbiota-driven metabolic activity. Biomarker candidates were validated in the external cohort.</p><p><strong>Conclusion: </strong>The airway microbiota and metabolites are intricately linked to asthma exacerbations, with distinct patterns between EA and NEA. These findings highlight their potential as diagnostic biomarkers and therapeutic targets for personalized asthma management.</p>","PeriodicalId":15079,"journal":{"name":"Journal of Asthma and Allergy","volume":"18 ","pages":"1003-1022"},"PeriodicalIF":3.7000,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12174932/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Asthma and Allergy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2147/JAA.S521800","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"ALLERGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Asthma is a chronic, heterogeneous disease driven by inflammatory phenotypes, primarily eosinophilic asthma (EA) and neutrophilic asthma (NEA). While allergen triggers are well-known, the role of the airway microbiome and metabolites in asthma exacerbations remains poorly understood.
Methods: We recruited 64 participants (24 EA, 20 NEA, 20 healthy controls [HC]) for the discovery cohort, with validation in an external cohort (10 EA, 8 NEA, 8 HC). Induced sputum samples were analyzed using 16S rRNA sequencing to profile bacterial composition and non-targeted metabolomics to assess airway metabolites. Random forest models identified diagnostic markers, validated in the external cohort.
Results: Significant shifts in airway microbiota were observed, particularly between NEA and HC, and between EA and NEA. Four bacterial general-Stenotrophomonas, Streptococcus, Achromobacter, and Neisseria-were consistently identified across groups. Veillonella was more abundant in NEA vs HC, while Achromobacter was enriched in NEA vs EA, indicating distinct microbial signatures. Metabolomic profiling revealed distinct pathways: pyrimidine metabolism (EA vs HC), tryptophan metabolism (NEA vs HC), and arachidonic acid metabolism (EA vs NEA). Microbial-metabolite correlations indicated microbiota-driven metabolic activity. Biomarker candidates were validated in the external cohort.
Conclusion: The airway microbiota and metabolites are intricately linked to asthma exacerbations, with distinct patterns between EA and NEA. These findings highlight their potential as diagnostic biomarkers and therapeutic targets for personalized asthma management.
背景:哮喘是一种由炎症表型驱动的慢性异质性疾病,主要是嗜酸性哮喘(EA)和嗜中性哮喘(NEA)。虽然过敏原触发是众所周知的,但气道微生物组和代谢物在哮喘恶化中的作用仍然知之甚少。方法:我们招募了64名参与者(24名EA, 20名NEA, 20名健康对照[HC])作为发现队列,并在外部队列(10名EA, 8名NEA, 8名HC)中进行验证。使用16S rRNA测序分析诱导痰样本的细菌组成,并使用非靶向代谢组学评估气道代谢物。随机森林模型确定了诊断标记,并在外部队列中得到验证。结果:观察到气道微生物群的显著变化,特别是NEA和HC之间,EA和NEA之间。四种细菌——窄养单胞菌、链球菌、无色杆菌和奈瑟菌——在各组中被一致地鉴定出来。在NEA和HC中,细微杆菌更丰富,而在NEA和EA中,无色杆菌更丰富,表明微生物特征不同。代谢组学分析显示了不同的途径:嘧啶代谢(EA vs HC),色氨酸代谢(NEA vs HC)和花生四烯酸代谢(EA vs NEA)。微生物-代谢物相关性表明微生物群驱动的代谢活性。候选生物标志物在外部队列中得到验证。结论:气道微生物群和代谢物与哮喘加重有着复杂的联系,EA和NEA之间具有不同的模式。这些发现突出了它们作为诊断性生物标志物和个性化哮喘治疗靶点的潜力。
期刊介绍:
An international, peer-reviewed journal publishing original research, reports, editorials and commentaries on the following topics: Asthma; Pulmonary physiology; Asthma related clinical health; Clinical immunology and the immunological basis of disease; Pharmacological interventions and new therapies.
Although the main focus of the journal will be to publish research and clinical results in humans, preclinical, animal and in vitro studies will be published where they shed light on disease processes and potential new therapies.