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. 2023 Jun 14;31(6):1054-1070.e9.
doi: 10.1016/j.chom.2023.04.018. Epub 2023 May 18.

Airway dysbiosis accelerates lung function decline in chronic obstructive pulmonary disease

Weijie Liang  1 , Yuqiong Yang  2 , Shenhai Gong  3 , Mingyuan Wei  1 , Yingfei Ma  4 , Ruipei Feng  1 , Jingyuan Gao  1 , Xiaomin Liu  1 , Fuyi Tu  5 , Wei Ma  5 , Xinzhu Yi  1 , Zhenyu Liang  2 , Fengyan Wang  2 , Lingwei Wang  6 , Dandan Chen  6 , Wensheng Shu  1 , Bruce E Miller  7 , Ruth Tal-Singer  7 , Gavin C Donaldson  8 , Jadwiga A Wedzicha  8 , Dave Singh  9 , Tom M A Wilkinson  10 , Christopher E Brightling  11 , Rongchang Chen  12 , Nanshan Zhong  2 , Zhang Wang  13
Affiliations
Free article

Airway dysbiosis accelerates lung function decline in chronic obstructive pulmonary disease

Weijie Liang et al. Cell Host Microbe. .
Free article

Abstract

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.

Keywords: COPD; airway microbiome; bacteriophage; homocysteine; lung function decline; multi-omics.

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Conflict of interest statement

Declaration of interests B.E.M. was an employee of GlaxoSmithKline (GSK) at the time of this study and is a current shareholder, outside the submitted work. R.T.-S. was an employee of GSK at the time of this study and is a current shareholder, reports personal fees from Immunomet, Vocalis Health, Teva, and Ena Therapeutics, and reports share options in ENA Respiratory, outside the submitted work. G.C.D. reports grants and personal fees from AstraZeneca and grants from Micom Ltd. and American Thoracic Society, outside the submitted work. J.A.W. reports grants from GSK, Johnson and Johnson, Novartis, Boehringer Ingelheim, and AstraZeneca, outside the submitted work. D.S. reports grants and personal fees from AstraZeneca, Boehringer Ingleheim, Chiesi, CSL Behring, EpiEndo, GSK, Kinaset Therapeutics, Novartis, Pulmatrix, Sanofi, Therevance and Verona, personal fees from Aerogen, Cipla, Genentech, Glenmark, Menarini, and Pfizer and Teva, outside the submitted work. T.M.A.W. reports grants and personal fees from AstraZeneca, GSK, Janssen, Sanofi, and Synairgen, personal fees from Boehringer Ingelheim, OM Pharma and MMH, outside the submitted work. C.E.B. reports grants and personal fees from 4DPharma, AstraZeneca/MedImmune, Boehringer Ingelheim, Chiesi, Genentech, Gossamer, GSK, Mologics, Novartis, Regeneron, Sanofi, and Teva, outside the submitted work.