Abstract
Background: Increasing evidences showed that the lung microbiota plays an important role in the pathogenesis of COPD and contributes COPD exacerbation. Aim: We investigated the impact of Azithormycin (AZM) and inhaled corticosteroid (ICS) on the lung microbiota and pulmonary metabolites in murine model of COPD. Methods: C57BL/6 WT mice were instilled intra-tracheally with porcine pancreatic elastase weekly for a month, which induced emphysema. We treated these mice with AZM and two kinds of ICS-Budesonide (BUD) and Fluticasone (FLU) for 1 month. Bronchoalveolar lavage fluid were collected for lung microbiota (using 16S RNA sequencing), pulmonary metabolites(using [GC-TOF-MS]), inflammation markers and immune cells analysis. Results: Our data showed that COPD mice treated with AZM, BUD and FLU reduced alveolar macrophage and FLU-treated COPD mice further reduced neutrophil compared with those treated with saline and PPE. Moreover, most cytokines decreased after mice treated with AZM, BUD and FLU. Furthermore, AZM, BUD and FLU-treated COPD mice increased alpha diversity of lung microbiota compared with those with PPE-treated and saline-treated. Interestingly, the PCoA analysis also showed that BUD and FLU-treated COPD mice had changed with similar lung microbiota and selected some specific pathogenic bacteria (e.g. Bacteriodes and Probacteria). Using the GC-TOF-MS method, we identified the “Cycloleucine” (an active immunosuppressive agent), was significantly higher in FLU-treated COPD mice than BUD-treated group. Conclusions: We demonstrated ICS-treated COPD mice significantly reduce airway inflammation and increase alpha diversity but select some specific pathogenic bacteria.
Published Version
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