Laboratory of Pharmaceutical Microbiology, Ghent University, Ghent, Belgium.
Microbiome and Host Health Programme, South Australian Health and Medical Research Institute (SAHMRI), Adelaide, Australia.
Respir Res. 2024 Oct 12;25(1):368. doi: 10.1186/s12931-024-02983-z.
Chronic airway disease (CAD) is characterized by chronic airway inflammation and colonization of the lungs by pro-inflammatory pathogens. However, while various other bacterial species are present in the lower airways, it is not fully understood how they influence inflammation. We aimed to identify novel anti-inflammatory species present in lower airway samples of patients with CAD.
Paired sputum microbiome and inflammatory marker data of adults with CAD across three separate cohorts (Australian asthma and bronchiectasis, Scottish bronchiectasis) was analyzed using Linear discriminant analysis Effect Size (LEfSE) and Spearman correlation analysis to identify species associated with a low inflammatory profile in patients.
We identified the genus Aggregatibacter as more abundant in patients with lower levels of airway inflammatory markers in two CAD cohorts (Australian asthma and bronchiectasis). In addition, the relative abundance of Aggregatibacter was inversely correlated with sputum IL-8 (Australian bronchiectasis) and IL-1β levels (Australian asthma and bronchiectasis). Subsequent in vitro testing, using a physiologically relevant three-dimensional lung epithelial cell model, revealed that Aggregatibacter spp. (i.e. A. actinomycetemcomitans, A. aphrophilus) and their cell-free supernatant exerted anti-inflammatory activity without influencing host cell viability.
These findings suggest that Aggregatibacter spp. might act to reduce airway inflammation in CAD patients.
慢性气道疾病(CAD)的特征是慢性气道炎症和促炎病原体对肺部的定植。然而,虽然在下呼吸道存在各种其他细菌物种,但它们如何影响炎症尚不完全清楚。我们旨在鉴定 CAD 患者下气道样本中存在的新型抗炎物种。
使用线性判别分析效应大小(LEfSE)和 Spearman 相关性分析,对来自三个独立队列(澳大利亚哮喘和支气管扩张症、苏格兰支气管扩张症)的成年 CAD 患者的配对痰微生物组和炎症标志物数据进行分析,以鉴定与患者低炎症特征相关的物种。
我们发现,在两个 CAD 队列(澳大利亚哮喘和支气管扩张症)中,呼吸道炎症标志物水平较低的患者中 Aggregatibacter 属更为丰富。此外,Aggregatibacter 的相对丰度与痰 IL-8(澳大利亚支气管扩张症)和 IL-1β 水平呈负相关(澳大利亚哮喘和支气管扩张症)。随后的体外试验,使用生理相关的三维肺上皮细胞模型,表明 Aggregatibacter 属(即 A. actinomycetemcomitans、A. aphrophilus)及其无细胞上清液具有抗炎活性,而不影响宿主细胞活力。
这些发现表明,Aggregatibacter 属可能有助于减轻 CAD 患者的气道炎症。