Sputum exosomal microRNAs profiling reveals critical pathways modulated by Pseudomonas aeruginosa colonization in bronchiectasis

Our findings have clinical implications. Identification of sputum exosomal miRNA helps explore the important biological pathways underlying the pathogenesis of bronchiectasis, thus unraveling candidate targets for future interventions of PA colonization. Apart from canonical inflammatory pathways, we have unraveled the modulation of longevity regulation pathway which opens a new avenue for exploring how PA colonization interacts with the airway epithelium. The significant correlation between sputum inflammatory biomarkers and miR-92b-5p and miR-223-3p provided further evidence on the unresolved inflammation in the PA-colonized microenvironment. However, causality cannot be inferred based on the current study design. Patients collected spontaneous sputum when clinically stable, and were followed-up to determine bacterial colonization status. Pseudomonas aeruginosa colonization is defined as sputum culture positive of Pseudomonas aeruginosa for at least two occasions (at least three months apart) within one year, when clinically stable during the longitudinal follow-up. Bronchiectasis patients were stratified into Pseudomonas aeruginosa and non-Pseudomonas aeruginosa group (unmet the criteria of Pseudomonas aeruginosa colonization). 2 different colonization status in stable bronchiectasis patients were divided. Induced sputum were collected in healthy subjects. All sputum samples were completed by exosomal miRNA sequencing.