Institute of Ecological Sciences, School of Life Sciences, South China Normal University, Guangzhou, Guangdong Province, China.
First Affiliated Hospital of Guangzhou Medical University, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, State Key Laboratory of Respiratory Disease, Guangzhou, Guangdong Province, China.
Cell Host Microbe. 2023 Jun 14;31(6):1054-1070.e9. doi: 10.1016/j.chom.2023.04.018. Epub 2023 May 18.
Progressive lung function decline is a hallmark of chronic obstructive pulmonary disease (COPD). Airway dysbiosis occurs in COPD, but whether it contributes to disease progression remains unknown. Here, we show, through a longitudinal analysis of two cohorts involving four UK centers, that baseline airway dysbiosis in COPD patients, characterized by the enrichment of opportunistic pathogenic taxa, associates with a rapid forced expiratory volume in 1 s (FEV) decline over 2 years. Dysbiosis associates with exacerbation-related FEV fall and sudden FEV fall at stability, contributing to long-term FEV decline. A third cohort in China further validates the microbiota-FEV-decline association. Human multi-omics and murine studies show that airway Staphylococcus aureus colonization promotes lung function decline through homocysteine, which elicits a neutrophil apoptosis-to-NETosis shift via the AKT1-S100A8/A9 axis. S. aureus depletion via bacteriophages restores lung function in emphysema mice, providing a fresh approach to slow COPD progression by targeting the airway microbiome.
肺功能进行性下降是慢性阻塞性肺疾病（COPD）的标志。COPD 存在气道菌群失调，但它是否导致疾病进展尚不清楚。在这里，我们通过涉及四个英国中心的两个队列的纵向分析表明，COPD 患者的基线气道菌群失调，其特征是机会性病原体分类群的富集，与 2 年内快速用力呼气量（FEV）下降相关。菌群失调与与加重相关的 FEV 下降和稳定性下的突然 FEV 下降相关，导致长期 FEV 下降。中国的第三个队列进一步验证了微生物群与 FEV 下降的关联。人类多组学和小鼠研究表明，气道金黄色葡萄球菌定植通过同型半胱氨酸促进肺功能下降，通过 AKT1-S100A8/A9 轴引发中性粒细胞凋亡至 NETosis 转变。通过噬菌体耗竭金黄色葡萄球菌可恢复肺气肿小鼠的肺功能，通过靶向气道微生物组为减缓 COPD 进展提供了一种新方法。
