Altered exosomal microRNA profiles in bronchoalveolar lavage fluid can mediate metabolism in patients with Acinetobacter baumannii ventilator-associated pneumonia

Background: Ventilator-associated pneumonia (VAP) is a major public health problem and is most commonly caused by Acinetobacter baumannii (Ab) infection. In our study, we investigated the profiles of exosomal microRNAs (miRNAs) extracted from the bronchoalveolar lavage fluid (BALF) and serum of patients with Acinetobacter baumannii ventilator-associated pneumonia (Ab-VAP). We also examined the serum metalx)lomic profiles of these patients. Our aim was to study the associations between lung tissuederived exosomal miRNAs and changes in global metabolism in patients with Ab-VAP. Methods: Consecutively sampled patients admitted to an intensive care unit (ICU) for pulmonary infection treatment were enrolled in this study. Demographic information and biochemical measurements were collected. Serum samples were obtained following overnight fasting on admission. Bronchoscopies were performed and BALF samples were collected from each patient. Exosomes were extracted using kits from System Biosciences (SBI) and miRNA sequencing was performed. Non-targeted metabolomics were used to express metabolic profiles. Results: We found significant changes in the miRNA profiles of patients with Ab-VAP; these changes occurred in both BALF exosomal miRNA and serum exosomal miRNA. Gene Ontology analysis further identified the function of miRNA in system metabolism. Serum metalxslomic profiles and ratios of biological significance were found to be differentially regulated in Ab-VAP patients. This differential regulation was correlated with the differential expression of miRNAs. Conclusions: Our data summarizes the dysregulation of serum metabolism and exosomal miRNA excretion that occurs in Ab-VAP patients. The correlation found between BALF exosomal miRNA and dysregulated metabolism, as indicated by the irregular expression of metabolites in the cellular metabolic pathway, highlights potential biomarkers for the diagnosis and treatment of Ab infection.