Altered Exosome microRNA Profile in Bronchoalveolar Lavage Is Correlated to Serum Metabolites Dysregulation in Patients with Acinetobacter baumannii Ventilator-Associated Pneumonia

Abstract

Background: Ventilator-associated pneumonia (VAP) is one of the major public health problems, most commonly caused by Acinetobacter baumannii (Ab). In this study, by investigating the BALF exosome microRNA and serum metabolomic profiles, we aim to study the association between lung tissue derived exosome microRNAs and global metabolism alteration among patients with VAP caused by Ab infection. Methods: Consecutive patients admitted for pulmonary infection were enrolled. Demographic and biochemical measurements were collected and serum samples were obtained after overnight fasting upon admission. Bronchoscopy was performed and bronchial lavage was collected for patients with pulmonary infection. Exosome was extracted using SBI kit and microRNA was sequenced afterwards. Nontargeted metabolomics was applied to demonstrate metabolic profiles. Results: We have found significant alteration of microRNA profile in BALF exosomes in the patients with VAP caused by Ab infection; Gene Ontology analysis further identified its function in systemic metabolism. The expression pattern of differential exosome microRNAs in the lung, liver and circulation implied that BALF exosomes from both immune and structural cells in the lung might carry microRNAs into the circulation to target systemic metabolism alteration. The serum metabolomic profile and ratio of biological significance were meanwhile differentially regulated, correlating to differential expression of microRNAs in VAP patients with Ab infection. Conclusions: Our data summarized the dysregulated serum metabolism and exosome microRNA excretion in VAP patients with Ab infection. The correlation between BALF exosome microRNA in cellular metabolic pathway and dysregulated metabolites highlight potential biomarkers and therapeutics for diagnosing and treating Ab infection. Funding Statement: This study was supported by National Natural Science Foundation of China (81500016，81800390), the Natural Science Foundation of Shaanxi province (2017JM8016, 2018KW067, 2016SF217), the Fundamental Research Funds for the Central Universities in China(1191329724, 191329849)， and the Clinical Research Award of the First Affiliated Hospital of Xi'an Jiaotong University, China ((No.XJTU1AF-CRF-2018-025). Declaration of Interests: The authors state: None declared. Ethics Approval Statement: Written informed consent was obtained according to the Declaration of Helsinki, and was approved by the ethics committee (IRB committee: Xi’an Jiaotong University, project approval number 2018(6-169)).