Airway dysbiosis accelerates lung function decline in chronic obstructive pulmonary disease

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作者：Weijie Liang, Yuqiong Yang, Shenhai Gong, Mingyuan Wei, Yingfei Ma, Ruipei Feng, Jingyuan Gao, Xiaomin Liu, Fuyi Tu, Wei Ma, Xinzhu Yi, Zhenyu Liang, Fengyan Wang, Lingwei Wang, Dandan Chen, Wensheng Shu, Bruce E. Miller, Ruth Tal-Singer, Gavin C. Donaldson, Jadwiga A. Wedzicha, Dave Singh, Tom M.A. Wilkinson, Christopher E. Brightling, Rongchang Chen, Nanshan Zhong, Zhang Wang
期刊：Cell Host & Microbe
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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 (FEV1) decline over 2 years. Dysbiosis associates with exacerbation-related FEV1 fall and sudden FEV1 fall at stability, contributing to long-term FEV1 decline. A third cohort in China further validates the microbiota-FEV1-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.