{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T22:40:42Z","timestamp":1776292842027,"version":"3.50.1"},"reference-count":40,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,4,2]],"date-time":"2022-04-02T00:00:00Z","timestamp":1648857600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Korea Health Industry Development  Institute","award":["HI21C1624"],"award-info":[{"award-number":["HI21C1624"]}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2020R1A2C1011455"],"award-info":[{"award-number":["2020R1A2C1011455"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPM"],"abstract":"<jats:p>Background: Previous studies reported a significant association between pneumonia outcome and the respiratory microbiome. There is increasing interest in the roles of bacterial extracellular vesicles (EVs) in various diseases. We studied the composition and function of microbiota-derived EVs in the plasma of patients receiving mechanical ventilation to evaluate whether they can be used as a diagnostic marker and to predict clinical outcomes. Methods: Plasma samples (n = 111) from 59 mechanically ventilated patients (41 in the pneumonia group; 24 in the nursing home and hospital-associated infection [NHAI] group) were prospectively collected on days one and seven. After isolating the bacterial EVs from plasma samples, nucleic acid was extracted for 16S rRNA gene pyrosequencing. The samples were evaluated to determine the \u03b1 and \u03b2 diversity, bacterial composition, and predicted functions. Results: Principal coordinates analysis revealed significantly different clustering of microbial EVs between the pneumonia and non-pneumonia groups. The proportions of Lactobacillus, Cutibacterium, and Sphingomonas were significantly different between the pneumonia and non-pneumonia groups. In addition, the abundances of Lactobacillus and Bifidobacterium were significantly higher in the non-NHAI than the NHAI group. In the analysis of \u03b2 diversity, the structure of microbial EVs differed significantly different between 28-day survivors and non-survivors (Bray-Curtis distance, p = 0.014). Functional profiling revealed significant differences between the pneumonia and non-pneumonia groups. The longitudinal change in predicted functions of microbial EV genes showed a significant difference between 28-day survivors and non-survivors. Conclusions: Bacterial microbiota\u2013derived EVs in the plasma have potential as diagnostic and prognostic markers for patients receiving mechanical ventilation. Further large prospective studies are needed to determine the clinical utility of plasma microbiota-EVs in intubated patients.<\/jats:p>","DOI":"10.3390\/jpm12040564","type":"journal-article","created":{"date-parts":[[2022,4,3]],"date-time":"2022-04-03T02:59:52Z","timestamp":1648954792000},"page":"564","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Metagenomic Analysis of Plasma Microbial Extracellular Vesicles in Patients Receiving Mechanical Ventilation: A Pilot Study"],"prefix":"10.3390","volume":"12","author":[{"given":"Jinkyeong","family":"Park","sequence":"first","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, Kyung Hee University Hospital at Gangdong, Kyung Hee University School of Medicine, Seoul 05278, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jae Jun","family":"Lee","sequence":"additional","affiliation":[{"name":"Institute of New Frontier Research Team, Hallym University College of Medicine, Chuncheon 24253, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1607-6777","authenticated-orcid":false,"given":"Yoonki","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, School of Medicine, Kangwon National University, Kangwon National University Hospital, Chuncheon 24289, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hochan","family":"Seo","sequence":"additional","affiliation":[{"name":"MD Healthcare Inc., Seoul 03293, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tae-Seop","family":"Shin","sequence":"additional","affiliation":[{"name":"MD Healthcare Inc., Seoul 03293, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3132-7706","authenticated-orcid":false,"given":"Ji Young","family":"Hong","sequence":"additional","affiliation":[{"name":"Institute of New Frontier Research Team, Hallym University College of Medicine, Chuncheon 24253, Korea"},{"name":"Division of Pulmonary and Critical Care Medicine, Department of Medicine, Chuncheon Sacred Heart Hospital, Hallym University Medical Center, Chuncheon 24253, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1038\/nri3837","article-title":"Immune modulation by bacterial outer membrane vesicles","volume":"15","author":"Ferrero","year":"2015","journal-title":"Nat. Rev. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1165\/rcmb.2017-0293TR","article-title":"Extracellular Vesicles: New Players in Lung Immunity","volume":"58","author":"Fujita","year":"2018","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.semcdb.2015.02.006","article-title":"Gram-negative and Gram-positive bacterial extracellular vesicles","volume":"40","author":"Kim","year":"2015","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1111\/all.12001","article-title":"Staphylococcus aureus-derived extracellular vesicles induce neutrophilic pulmonary inflammation via both Th1 and Th17 cell responses","volume":"67","author":"Kim","year":"2012","journal-title":"Allergy"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1111\/cea.12085","article-title":"Extracellular vesicles, especially derived from Gram-negative bacteria, in indoor dust induce neutrophilic pulmonary inflammation associated with both Th1 and Th17 cell responses","volume":"43","author":"Kim","year":"2013","journal-title":"Clin. Exp. Allergy"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e133","DOI":"10.1038\/cti.2017.6","article-title":"Microbiome effects on immunity, health and disease in the lung","volume":"6","author":"Shukla","year":"2017","journal-title":"Clin. Transl. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"101","DOI":"10.4168\/aair.2017.9.2.101","article-title":"Extracellular Vesicles, a Key Mediator to Link Environmental Microbiota to Airway Immunity","volume":"9","author":"Choi","year":"2017","journal-title":"Allergy Asthma Immunol. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e00559-18","DOI":"10.1128\/mBio.00559-18","article-title":"Immunomodulatory Effects of Pneumococcal Extracellular Vesicles on Cellular and Humoral Host Defenses","volume":"9","author":"Codemo","year":"2018","journal-title":"mBio"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1056\/NEJMoa1500245","article-title":"Community-Acquired Pneumonia Requiring Hospitalization among U.S. Adults","volume":"373","author":"Jain","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"101","DOI":"10.21037\/jeccm.2018.11.06","article-title":"Management of pneumonia in intensive care","volume":"2","author":"Morris","year":"2018","journal-title":"J. Emerg. Crit. Care Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1164\/rccm.201301-0079OC","article-title":"Risk factors for drug-resistant pathogens in community-acquired and healthcare-associated pneumonia","volume":"188","author":"Shindo","year":"2013","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Woo, S., Park, S.Y., Kim, Y., Jeon, J.P., Lee, J.J., and Hong, J.Y. (2020). The Dynamics of Respiratory Microbiota during Mechanical Ventilation in Patients with Pneumonia. J. Clin. Med., 9.","DOI":"10.3390\/jcm9030638"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.1111\/j.1398-9995.2010.02359.x","article-title":"Extracellular vesicles are key intercellular mediators in the development of immune dysfunction to allergens in the airways","volume":"65","author":"Shin","year":"2010","journal-title":"Allergy"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e45","DOI":"10.1164\/rccm.201908-1581ST","article-title":"Diagnosis and Treatment of Adults with Community-acquired Pneumonia. An Official Clinical Practice Guideline of the American Thoracic Society and Infectious Diseases Society of America","volume":"200","author":"Metlay","year":"2019","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e61","DOI":"10.1093\/cid\/ciw353","article-title":"Management of Adults with Hospital-acquired and Ventilator-associated Pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society","volume":"63","author":"Kalil","year":"2016","journal-title":"Clin. Infect. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1186\/s12967-020-02642-z","article-title":"Respiratory microbiome profiles differ by recent hospitalization and nursing home residence in patients on mechanical ventilation","volume":"18","author":"Baek","year":"2020","journal-title":"J. Transl. Med."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Kim, J.R., Han, K., Han, Y., Kang, N., Shin, T.S., Park, H.J., Kim, H., Kwon, W., Lee, S., and Kim, Y.K. (2021). Microbiome Markers of Pancreatic Cancer Based on Bacteria-Derived Extracellular Vesicles Acquired from Blood Samples: A Retrospective Propensity Score Matching Analysis. Biology, 10.","DOI":"10.3390\/biology10030219"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2882","DOI":"10.1093\/bioinformatics\/btv287","article-title":"Tax4Fun: Predicting functional profiles from metagenomic 16S rRNA data","volume":"31","author":"Asshauer","year":"2015","journal-title":"Bioinformatics"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1136\/gutjnl-2015-309800","article-title":"Metagenomic analysis of faecal microbiome as a tool towards targeted non-invasive biomarkers for colorectal cancer","volume":"66","author":"Yu","year":"2017","journal-title":"Gut"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"792","DOI":"10.4168\/aair.2020.12.5.792","article-title":"Diagnostic Models for Atopic Dermatitis Based on Serum Microbial Extracellular Vesicle Metagenomic Analysis: A Pilot Study","volume":"12","author":"Yang","year":"2020","journal-title":"Allergy Asthma Immunol. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1136\/gutjnl-2015-309728","article-title":"The gut microbiota plays a protective role in the host defence against pneumococcal pneumonia","volume":"65","author":"Schuijt","year":"2016","journal-title":"Gut"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"924","DOI":"10.3389\/fimmu.2018.00924","article-title":"Extracellular Vesicle: An Emerging Mediator of Intercellular Crosstalk in Lung Inflammation and Injury","volume":"9","author":"Lee","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"R31","DOI":"10.1186\/cc9978","article-title":"High levels of circulating leukocyte microparticles are associated with better outcome in acute respiratory distress syndrome","volume":"15","author":"Guervilly","year":"2011","journal-title":"Crit. Care"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1186\/s13054-017-1700-7","article-title":"Circulating microparticle levels are reduced in patients with ARDS","volume":"21","author":"Shaver","year":"2017","journal-title":"Crit. Care"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1111\/trf.13477","article-title":"Comprehensive description of blood microbiome from healthy donors assessed by 16S targeted metagenomic sequencing","volume":"56","author":"Paisse","year":"2016","journal-title":"Transfusion"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1136\/thoraxjnl-2016-209158","article-title":"The dynamics of the pulmonary microbiome during mechanical ventilation in the intensive care unit and the association with occurrence of pneumonia","volume":"72","author":"Zakharkina","year":"2017","journal-title":"Thorax"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s40168-016-0151-8","article-title":"Composition and dynamics of the respiratory tract microbiome in intubated patients","volume":"4","author":"Kelly","year":"2016","journal-title":"Microbiome"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e00064-17","DOI":"10.1128\/CMR.00064-17","article-title":"Clinical and Biological Features of Cutibacterium (Formerly Propionibacterium) avidum, an Underrecognized Microorganism","volume":"31","author":"Corvec","year":"2018","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/S0958-1669(96)80034-6","article-title":"The genus Sphingomonas: Physiology and ecology","volume":"7","author":"White","year":"1996","journal-title":"Curr. Opin. Biotechnol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1186\/s12931-018-0847-3","article-title":"Lower respiratory tract microbial composition was diversified in Pseudomonas aeruginosa ventilator-associated pneumonia patients","volume":"19","author":"Qi","year":"2018","journal-title":"Respir. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1186\/s13054-018-2167-x","article-title":"Synbiotics modulate gut microbiota and reduce enteritis and ventilator-associated pneumonia in patients with sepsis: A randomized controlled trial","volume":"22","author":"Shimizu","year":"2018","journal-title":"Crit. Care"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1038\/nrmicro2690","article-title":"Emerging molecular insights into the interaction between probiotics and the host intestinal mucosa","volume":"10","author":"Bron","year":"2011","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1128\/JCM.03561-13","article-title":"Methylobacterium and its role in health care-associated infection","volume":"52","author":"Kovaleva","year":"2014","journal-title":"J. Clin. Microbiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.jgar.2015.10.008","article-title":"Isolation of Acinetobacter radioresistens from a clinical sample in Bulgaria","volume":"4","author":"Savov","year":"2016","journal-title":"J. Glob. Antimicrob. Resist."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e00495","DOI":"10.1016\/j.idcr.2019.e00495","article-title":"Acinetobacter radioresistens infection with bacteremia and pneumonia","volume":"15","author":"Wang","year":"2019","journal-title":"IDCases"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1038\/ismej.2017.176","article-title":"Bacterial secretion of D-arginine controls environmental microbial biodiversity","volume":"12","author":"Alvarez","year":"2018","journal-title":"ISME J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2570S","DOI":"10.1093\/jn\/nxaa079","article-title":"Histidine Metabolism and Function","volume":"150","author":"Brosnan","year":"2020","journal-title":"J. Nutr."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1797","DOI":"10.1016\/j.ajpath.2019.05.021","article-title":"Identification of Metabolic Changes in Ileum, Jejunum, Skeletal Muscle, Liver, and Lung in a Continuous I.V. Pseudomonas aeruginosa Model of Sepsis Using Nontargeted Metabolomics Analysis","volume":"189","author":"Ilaiwy","year":"2019","journal-title":"Am. J. Pathol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.apsb.2019.12.003","article-title":"Xenobiotic receptors in mediating the effect of sepsis on drug metabolism","volume":"10","author":"Lv","year":"2020","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1093\/jn\/134.3.489","article-title":"Glutathione metabolism and its implications for health","volume":"134","author":"Wu","year":"2004","journal-title":"J. Nutr."}],"container-title":["Journal of Personalized Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4426\/12\/4\/564\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:48:47Z","timestamp":1760136527000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4426\/12\/4\/564"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,2]]},"references-count":40,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2022,4]]}},"alternative-id":["jpm12040564"],"URL":"https:\/\/doi.org\/10.3390\/jpm12040564","relation":{},"ISSN":["2075-4426"],"issn-type":[{"value":"2075-4426","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,2]]}}}