2. Academic Validation
  3. Airway dysbiosis accelerates lung function decline in chronic obstructive pulmonary disease

Airway dysbiosis accelerates lung function decline in chronic obstructive pulmonary disease

  • Cell Host Microbe. 2023 May 16;S1931-3128(23)00167-1. doi: 10.1016/j.chom.2023.04.018.
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

Affiliations

  • 1 Institute of Ecological Sciences, School of Life Sciences, South China Normal University, Guangzhou, Guangdong Province, China.
  • 2 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.
  • 3 School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong Province, China.
  • 4 Shenzhen Key Laboratory of Synthetic Genomics, Guangdong Provincial Key Laboratory of Synthetic Genomics, CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong Province, China.
  • 5 Institute of Statistics and Big Data, Renmin University of China, Beijing, China.
  • 6 Pulmonary and Critical Care Department, Shenzhen Institute of Respiratory Diseases, Shenzhen People's Hospital, Shenzhen, Guangdong Province, China.
  • 7 COPD Foundation, Washington, DC, USA.
  • 8 National Heart and Lung Institute, Imperial College London, London, UK.
  • 9 Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester, Manchester University NHS Foundation Trust, Manchester, UK.
  • 10 NIHR Southampton Respiratory Biomedical Research Unit, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
  • 11 Institute for Lung Health, Leicester NIHR Biomedical Research Centre, Department of Respiratory Sciences, University of Leicester, Leicester, UK.
  • 12 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; Pulmonary and Critical Care Department, Shenzhen Institute of Respiratory Diseases, Shenzhen People's Hospital, Shenzhen, Guangdong Province, China.
  • 13 Institute of Ecological Sciences, School of Life Sciences, South China Normal University, Guangzhou, Guangdong Province, China. Electronic address: wangz@m.scnu.edu.cn.
PMID: 37207649 DOI: 10.1016/j.chom.2023.04.018
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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