Longitudinal Analysis of Lung Microbiome, Immune Response, and Metabolism in Ventilator-Associated Pneumonia: A Cohort Study.

Longitudinal Analysis of Lung Microbiome, Immune Response, and Metabolism in Ventilator-Associated Pneumonia: A Cohort Study. | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Longitudinal Analysis of Lung Microbiome, Immune Response, and Metabolism in Ventilator-Associated Pneumonia: A Cohort Study. Ingrid Gisell BUstos Moya, Cristian Camilo Serrano, Jose Leonardo Guerrero, and 13 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6247242/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Rationale: Ventilator-associated pneumonia (VAP) is a common complication in patients under invasive mechanical ventilation (IMV), yet its underlying mechanisms remain poorly understood. This study investigated the lung microbiome, inflammatory response, and metabolism in patients undergoing IMV to identify factors that may predispose them to developing VAP. Objectives: To investigate how changes in lung microbiome composition, inflammatory response, and metabolic profiles may predispose patients undergoing IMV to develop VAP. Methods: Patients requiring IMV for at least 48 hours due to non-infectious respiratory failure were enrolled. Bronchoalveolar lavage (BAL) samples were collected at baseline, upon VAP diagnosis, or after 72 hours for non-VAP cases. DNA sequencing, cytokine quantification, and metabolomic analyses were performed. Results: Of the 80 patients, 41 (51%) developed VAP. No significant differences in alpha or beta diversity of the lung microbiome were observed between groups. However, both groups showed changes in microbiome composition over time, suggesting an impact of IMV. TNF-α lung levels were significantly higher in VAP patients, while lung IL-1β increased in all patients. Metabolomic analysis revealed shifts in pentose phosphate and citric acid cycle pathways, indicating a transition to anaerobic metabolism in the lungs of VAP patients. Conclusions: Mechanical ventilation drives dynamic changes in the lung microbiome, independent of VAP development. Lung inflammation with elevated TNF-α was documented in VAP, while IL-1β reflected the broader effects of IMV. Finally, metabolic evidence of anaerobic adaptation in the lungs of patients with VAP was observed. Microbiota Host Microbial Interaction Metabolomics Ventilator-Associated Pneumonia (VAP) Full Text Supplementary Files OnlineDataSupplementMicroVAP.pdf STROBEStatementICMMicroVAP.pdf Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6247242","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":432757042,"identity":"f50d8a5d-4de5-4240-8b54-64206f5dff11","order_by":0,"name":"Ingrid Gisell BUstos Moya","email":"","orcid":"","institution":"University of La Sabana Faculty of Medicine: Universidad de la Sabana Facultad de Medicina","correspondingAuthor":false,"prefix":"","firstName":"Ingrid","middleName":"Gisell BUstos","lastName":"Moya","suffix":""},{"id":432757043,"identity":"46235f42-9454-4d6a-9a2e-9a9139565a62","order_by":1,"name":"Cristian Camilo Serrano","email":"","orcid":"","institution":"University of La Sabana Faculty of Medicine: Universidad de la Sabana Facultad de Medicina","correspondingAuthor":false,"prefix":"","firstName":"Cristian","middleName":"Camilo","lastName":"Serrano","suffix":""},{"id":432757044,"identity":"a40e3bea-036f-4b28-8da9-835f94dbd87b","order_by":2,"name":"Jose Leonardo Guerrero","email":"","orcid":"","institution":"Universidad de Los Andes","correspondingAuthor":false,"prefix":"","firstName":"Jose","middleName":"Leonardo","lastName":"Guerrero","suffix":""},{"id":432757045,"identity":"ccf65279-b9a5-4fe7-be3d-b7e18cf2e23f","order_by":3,"name":"Jennifer M Baker","email":"","orcid":"","institution":"University of Michigan","correspondingAuthor":false,"prefix":"","firstName":"Jennifer","middleName":"M","lastName":"Baker","suffix":""},{"id":432757046,"identity":"afb270e2-d1d8-4724-bced-b3ba353a6b98","order_by":4,"name":"Christopher Brown","email":"","orcid":"","institution":"University of Michigan","correspondingAuthor":false,"prefix":"","firstName":"Christopher","middleName":"","lastName":"Brown","suffix":""},{"id":432757047,"identity":"5b5c96dd-cd25-4e46-90e8-b6bdc0342555","order_by":5,"name":"Nicole Falkowski","email":"","orcid":"","institution":"University of Michigan","correspondingAuthor":false,"prefix":"","firstName":"Nicole","middleName":"","lastName":"Falkowski","suffix":""},{"id":432757048,"identity":"01b46480-f0b9-407d-86c2-a5d8c91a17b4","order_by":6,"name":"Piyush Ranjan","email":"","orcid":"","institution":"University of Michigan","correspondingAuthor":false,"prefix":"","firstName":"Piyush","middleName":"","lastName":"Ranjan","suffix":""},{"id":432757049,"identity":"6bfc9824-f975-48f3-af22-9e93a218e518","order_by":7,"name":"Luis Alejandro Acosta","email":"","orcid":"","institution":"Universidad de La Sabana","correspondingAuthor":false,"prefix":"","firstName":"Luis","middleName":"Alejandro","lastName":"Acosta","suffix":""},{"id":432757050,"identity":"e78ac4ca-99c2-4c72-ae5b-d1721bd64587","order_by":8,"name":"Lina Marcela Mendez","email":"","orcid":"","institution":"Universidad de La Sabana","correspondingAuthor":false,"prefix":"","firstName":"Lina","middleName":"Marcela","lastName":"Mendez","suffix":""},{"id":432757051,"identity":"2ce6d450-b8f0-4e0b-8f1f-c52f34c632e8","order_by":9,"name":"Norberto Gonzalez Juarbe","email":"","orcid":"","institution":"University of Maryland at College Park: University of Maryland","correspondingAuthor":false,"prefix":"","firstName":"Norberto","middleName":"Gonzalez","lastName":"Juarbe","suffix":""},{"id":432757052,"identity":"436e2040-e343-40a8-ac6d-1ec5d4382d3f","order_by":10,"name":"Alejandro Rodriguez","email":"","orcid":"","institution":"Joan XXIII University Hospital in Tarragona: Hospital Universitari de Tarragona Joan XXIII","correspondingAuthor":false,"prefix":"","firstName":"Alejandro","middleName":"","lastName":"Rodriguez","suffix":""},{"id":432757053,"identity":"bf3ad2ba-dcdb-4f80-807d-6883451b68eb","order_by":11,"name":"Monica Cala","email":"","orcid":"","institution":"Universidad de Los Andes","correspondingAuthor":false,"prefix":"","firstName":"Monica","middleName":"","lastName":"Cala","suffix":""},{"id":432757054,"identity":"42e25893-e7df-4f26-8a95-d3cd29c706cb","order_by":12,"name":"Ignacio Martin-Loeches","email":"","orcid":"","institution":"St James's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ignacio","middleName":"","lastName":"Martin-Loeches","suffix":""},{"id":432757055,"identity":"2eb8c8d5-7158-4228-b18e-89fe29c4fa61","order_by":13,"name":"Sanjay H. 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This study investigated the lung microbiome, inflammatory response, and metabolism in patients undergoing IMV to identify factors that may predispose them to developing VAP.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eObjectives: To investigate how changes in lung microbiome composition, inflammatory response, and metabolic profiles may predispose patients undergoing IMV to develop VAP.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMethods: Patients requiring IMV for at least 48 hours due to non-infectious respiratory failure were enrolled. Bronchoalveolar lavage (BAL) samples were collected at baseline, upon VAP diagnosis, or after 72 hours for non-VAP cases. DNA sequencing, cytokine quantification, and metabolomic analyses were performed.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eResults: Of the 80 patients, 41 (51%) developed VAP. No significant differences in alpha or beta diversity of the lung microbiome were observed between groups. However, both groups showed changes in microbiome composition over time, suggesting an impact of IMV. TNF-α lung levels were significantly higher in VAP patients, while lung IL-1β increased in all patients. Metabolomic analysis revealed shifts in pentose phosphate and citric acid cycle pathways, indicating a transition to anaerobic metabolism in the lungs of VAP patients.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eConclusions: Mechanical ventilation drives dynamic changes in the lung microbiome, independent of VAP development. Lung inflammation with elevated TNF-α was documented in VAP, while IL-1β reflected the broader effects of IMV. Finally, metabolic evidence of anaerobic adaptation in the lungs of patients with VAP was observed.\u003c/p\u003e","manuscriptTitle":"Longitudinal Analysis of Lung Microbiome, Immune Response, and Metabolism in Ventilator-Associated Pneumonia: A Cohort Study.","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-03-31 11:29:57","doi":"10.21203/rs.3.rs-6247242/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"1f9c6cc8-b43f-4a42-a57e-40594b20b637","owner":[],"postedDate":"March 31st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-04-20T14:59:29+00:00","versionOfRecord":[],"versionCreatedAt":"2025-03-31 11:29:57","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6247242","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"identity":"rs-6247242","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}