Frequent exacerbators of chronic obstructive pulmonary disease have distinguishable sputum microbiome signatures during clinical stability

Introduction: Frequent exacerbation phenotype of chronic obstructive pulmonary disease (COPD) represents a more concerning disease subgroup requiring better prevention and intervention, of which airway microbiome provides new perspective for further exploration. Methods: To investigate whether frequent exacerbators of COPD have distinguishable sputum microbiome during clinical stability, COPD patients at high disease grades with or without frequent exacerbation were recruited for sputum microbiome analysis. Sputum samples were collected during clinical stability and underwent 16S rRNA sequencing, which was then subjected for amplicon sequence variants (ASVs)-based microbiome analysis. Results: Our results revealed that compared with healthy controls and infrequent exacerbators, frequent COPD exacerbators have distinguishably dysbiotic sputum microbiome, as featured by fewer ASVs features, lower alpha diversity, distinct beta diversity patterns. Further taxonomic compositional analysis illustrated the structural distinctions between frequent COPD exacerbators and infrequent exacerbators at differential taxa levels and highlighted Stenotrephomonas due to its prominent elevation in frequent COPD exacerbators, providing a promising candidate for further exploration of microbiome biomarker. Moreover, we also demonstrated that frequent exacerbation phenotype is distinguishable from infrequent exacerbation phenotype with respect of functional implications. Conclusion: Our study demonstrated the first positive correlation between the frequent exacerbation phenotype of COPD and the sputum microbiome during clinical stability in a single-center Chinese COPD cohort and provide potential diagnostic and therapeutic targets for further investigation.