Sputum Microbiota Compositions Correlate With Metabolome and Clinical Outcomes of COPD‐Bronchiectasis Association: A Prospective Cohort Study

Bronchiectasis frequently co-exists with chronic obstructive pulmonary disease (COPD-bronchiectasis association [CBA]). We compared the microbiota and metabolome of bronchiectasis with (BO) and without airflow obstruction (BNO), COPD, and CBA. We determined how microbiota compositions correlated with clinical characteristics and exacerbations of CBA. We prospectively recruited outpatients with BNO (<i>n</i> = 104), BO (<i>n</i> = 51), COPD (<i>n</i> = 33), and CBA (<i>n</i> = 70). We sampled at stead-state and exacerbation, and profiled sputum microbiota via 16S rRNA sequencing and metabolome via liquid chromatography/mass spectrometry. Sputum microbiota and metabolome profiles of CBA separated from COPD (<i>P</i> < 0.05) but not bronchiectasis, partly driven by Proteobacteria enrichment in CBA. An increasing microbial interaction but not microbiota compositions were identified at exacerbation. Pseudomonadaceae-dominant CBA yielded lower Shannon-Wiener diversity index (<i>P</i> < 0.001), greater bronchiectasis severity (<i>P</i> < 0.05) and higher future exacerbation risk (HR 2.46, 95% CI: 1.34-4.52, <i>P</i> < 0.001) than other genera-dominant CBA. We found a clear metabolite discrimination between CBA and COPD. Most of up-regulated metabolites identified in CBA, were amino acids metabolites, which indicated that the accumulation of amino acids metabolites was related to the alteration of airway microbiota. To conclude, airway structural changes, but not airflow limitation, correlate more profoundly with microbiota and metabolome profiles (e.g. partly via Pseudomonadaceae-amino acids metabolism links), shaping clinical outcomes of CBA.