National Heart & Lung Institute, Imperial College London, London, UK.
Respiratory Department, Faculty of Medicine, Southampton University, Southampton, UK.
Clin Transl Med. 2024 Sep;14(9):e70007. doi: 10.1002/ctm2.70007.
Severe asthma (SA) encompasses several clinical phenotypes with a heterogeneous airway microbiome. We determined the phenotypes associated with a low α-diversity microbiome.
Metagenomic sequencing was performed on sputum samples from SA participants. A threshold of 2 standard deviations below the mean of α-diversity of mild-moderate asthma and healthy control subjects was used to define those with an abnormal abundance threshold as relative dominant species (RDS).
Fifty-one out of 97 SA samples were classified as RDSs with Haemophilus influenzae RDS being most common (n = 16), followed by Actinobacillus unclassified (n = 10), Veillonella unclassified (n = 9), Haemophilus aegyptius (n = 9), Streptococcus pseudopneumoniae (n = 7), Propionibacterium acnes (n = 5), Moraxella catarrhalis (n = 5) and Tropheryma whipplei (n = 5). Haemophilus influenzae RDS had the highest duration of disease, more exacerbations in previous year and greatest number on daily oral corticosteroids. Hierarchical clustering of RDSs revealed a C2 cluster (n = 9) of highest relative abundance of exclusively Haemophilus influenzae RDSs with longer duration of disease and higher sputum neutrophil counts associated with enrichment pathways of MAPK, NF-κB, TNF, mTOR and necroptosis, compared to the only other cluster, C1, which consisted of 7 Haemophilus influenzae RDSs out of 42. Sputum transcriptomics of C2 cluster compared to C1 RDSs revealed higher expression of neutrophil extracellular trap pathway (NETosis), IL6-transignalling signature and neutrophil activation.
We describe a Haemophilus influenzae cluster of the highest relative abundance associated with neutrophilic inflammation and NETosis indicating a host response to the bacteria. This phenotype of severe asthma may respond to specific antibiotics.
严重哮喘（SA）包含具有异质气道微生物组的几种临床表型。我们确定了与低α多样性微生物组相关的表型。
对 SA 参与者的痰样本进行宏基因组测序。使用轻度至中度哮喘和健康对照受试者α多样性平均值的 2 个标准差以下的阈值来定义异常丰度阈值作为相对优势种（RDS）。
97 例 SA 样本中有 51 例被归类为 RDS，其中最常见的是流感嗜血杆菌 RDS（n=16），其次是未分类的放线杆菌（n=10）、未分类的韦荣球菌（n=9）、埃及嗜血杆菌（n=9）、肺炎链球菌（n=7）、痤疮丙酸杆菌（n=5）、卡他莫拉菌（n=5）和旋毛虫（n=5）。流感嗜血杆菌 RDS 的疾病持续时间最长，前一年发作次数更多，每日口服皮质类固醇的数量也最多。RDS 的层次聚类显示出 C2 簇（n=9），其中包含最高相对丰度的流感嗜血杆菌 RDS，其疾病持续时间更长，痰中性粒细胞计数更高，与 MAPK、NF-κB、TNF、mTOR 和坏死性凋亡的富集途径相关，与仅包含 42 例中的 7 例流感嗜血杆菌 RDS 的唯一另一个 C1 簇相比。与 C1 RDS 相比，C2 簇的痰转录组学显示出更高的中性粒细胞胞外陷阱途径（NETosis）、IL6 信号转导特征和中性粒细胞激活的表达。
我们描述了一个与中性粒细胞炎症和 NETosis 相关的最高相对丰度的流感嗜血杆菌簇，表明这是宿主对细菌的反应。这种严重哮喘的表型可能对特定的抗生素有反应。
