National Heart & Lung Institute & Data Science Institute, Imperial College London, London, UK.
Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore City, Singapore.
Allergy. 2023 Nov;78(11):2906-2920. doi: 10.1111/all.15776. Epub 2023 Jun 7.
Because of altered airway microbiome in asthma, we analysed the bacterial species in sputum of patients with severe asthma.
Whole genome sequencing was performed on induced sputum from non-smoking (SAn) and current or ex-smoker (SAs/ex) severe asthma patients, mild/moderate asthma (MMA) and healthy controls (HC). Data were analysed by asthma severity, inflammatory status and transcriptome-associated clusters (TACs).
α-diversity at the species level was lower in SAn and SAs/ex, with an increase in Haemophilus influenzae and Moraxella catarrhalis, and Haemophilus influenzae and Tropheryma whipplei, respectively, compared to HC. In neutrophilic asthma, there was greater abundance of Haemophilus influenzae and Moraxella catarrhalis and in eosinophilic asthma, Tropheryma whipplei was increased. There was a reduction in α-diversity in TAC1 and TAC2 that expressed high levels of Haemophilus influenzae and Tropheryma whipplei, and Haemophilus influenzae and Moraxella catarrhalis, respectively, compared to HC. Sputum neutrophils correlated positively with Moraxella catarrhalis and negatively with Prevotella, Neisseria and Veillonella species and Haemophilus parainfluenzae. Sputum eosinophils correlated positively with Tropheryma whipplei which correlated with pack-years of smoking. α- and β-diversities were stable at one year.
Haemophilus influenzae and Moraxella catarrhalis were more abundant in severe neutrophilic asthma and TAC2 linked to inflammasome and neutrophil activation, while Haemophilus influenzae and Tropheryma whipplei were highest in SAs/ex and in TAC1 associated with highest expression of IL-13 type 2 and ILC2 signatures with the abundance of Tropheryma whipplei correlating positively with sputum eosinophils. Whether these bacterial species drive the inflammatory response in asthma needs evaluation.
由于哮喘患者气道微生物组发生改变，我们分析了重度哮喘患者痰液中的细菌种类。
对非吸烟（SAn）和当前或曾吸烟（SAs/ex）的重度哮喘患者、轻度/中度哮喘（MMA）患者和健康对照者（HC）的诱导痰进行全基因组测序。根据哮喘严重程度、炎症状态和转录组相关聚类（TAC）分析数据。
与 HC 相比，SAn 和 SAs/ex 的种水平α多样性较低，分别表现为流感嗜血杆菌和卡他莫拉菌以及流感嗜血杆菌和土拉弗朗西斯菌增加。在嗜中性粒细胞性哮喘中，流感嗜血杆菌和卡他莫拉菌的丰度更高，在嗜酸性粒细胞性哮喘中，土拉弗朗西斯菌增加。TAC1 和 TAC2 中α多样性降低，TAC1 和 TAC2 分别表达高水平的流感嗜血杆菌和土拉弗朗西斯菌以及流感嗜血杆菌和卡他莫拉菌。与 HC 相比，痰液中性粒细胞与卡他莫拉菌呈正相关，与普雷沃菌、奈瑟菌和韦荣球菌属以及副流感嗜血杆菌呈负相关。痰液嗜酸性粒细胞与土拉弗朗西斯菌呈正相关，与吸烟包年数呈正相关。α-和β-多样性在一年时保持稳定。
在重度嗜中性粒细胞性哮喘中，流感嗜血杆菌和卡他莫拉菌更为丰富，而与炎症小体和中性粒细胞激活相关的 TAC2 与 Haemophilus parainfluenzae 相关；在 SAs/ex 中，流感嗜血杆菌和土拉弗朗西斯菌含量最高，与 TAC1 相关，TAC1 与 IL-13 型 2 和 ILC2 标志物的高表达相关，与痰液嗜酸性粒细胞数呈正相关。这些细菌种类是否能驱动哮喘中的炎症反应，需要进一步评估。
