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

Abstract

Background: Pseudomonas aeruginosa (PA) colonization confers poor prognosis in bronchiectasis. However, the biomarkers and biological pathways underlying these associations are unclear. Objective: To identify the roles of PA colonization in bronchiectasis by exploring for sputum exosomal microRNA profiles. Methods: We enrolled 98 patients with clinically stable bronchiectasis and 17 healthy subjects. Sputum was split for bacterial culture and exosomal microRNA sequencing, followed by validation with quantitative polymerase chain reaction. Bronchiectasis patients were stratified into PA and non-PA colonization groups based on sputum culture findings. We applied Gene Ontology and Kyoto Encyclopedia of Genes and Genome pathway enrichment analysis to explore biological pathways corresponding to the differentially expressed microRNAs (DEMs) associated with PA colonization. Results: Eighty-two bronchiectasis patients and 9 healthy subjects yielded sufficient sputum that passed quality control. We identified 10 overlap DEMs for the comparison between bronchiectasis patients and healthy subjects, and between PA and non-PA colonization group. Both miR-92b-5p and miR-223-3p could discriminate PA colonization (C-statistic >0.60) and independently correlated with PA colonization in multiple linear regression analysis. The differential expression of miR-92b-5p was validated by quantitative polymerase chain reaction (P<0.05), whereas the differential expression of miR-223 trended towards statistical significance (P=0.06). These DEMs, whose expression levels correlated significantly with sputum inflammatory biomarkers (interleukin-1β and interleukin-8) level, were implicated in the modulation of the nuclear factor-κB, phosphatidylinositol and longevity regulation pathways. Conclusion: Sputum exosomal microRNAs are implicated in PA colonization in bronchiectasis, highlighting candidate targets for therapeutic interventions to mitigate the adverse impacts conferred by PA colonization.