{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T00:44:49Z","timestamp":1776818689290,"version":"3.51.2"},"reference-count":54,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,7,6]],"date-time":"2022-07-06T00:00:00Z","timestamp":1657065600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,7,6]],"date-time":"2022-07-06T00:00:00Z","timestamp":1657065600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"NIHR Manchester Biochemical Research Centre"},{"DOI":"10.13039\/100011264","name":"FP7 People: Marie-Curie Actions","doi-asserted-by":"publisher","award":["MC-IAPP BreathDx 611951"],"award-info":[{"award-number":["MC-IAPP BreathDx 611951"]}],"id":[{"id":"10.13039\/100011264","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011264","name":"FP7 People: Marie-Curie Actions","doi-asserted-by":"publisher","award":["MC-IAPP BreathDx 611951"],"award-info":[{"award-number":["MC-IAPP BreathDx 611951"]}],"id":[{"id":"10.13039\/100011264","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Crit Care"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Ventilator-associated pneumonia (VAP) is associated with high morbidity and health care costs, yet diagnosis remains a challenge. Analysis of airway microbiota by amplicon sequencing provides a possible solution, as pneumonia is characterised by a disruption of the microbiome. However, studies evaluating the diagnostic capabilities of microbiome analysis are limited, with a lack of alignment on possible biomarkers. Using bronchoalveolar lavage fluid (BALF) from ventilated adult patients suspected of VAP, we aimed to explore how key characteristics of the microbiome differ between patients with positive and negative BALF cultures and whether any differences could have a clinically relevant role.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>BALF from patients suspected of VAP was analysed using 16s rRNA sequencing in order to: (1) differentiate between patients with and without a positive culture; (2) determine if there was any association between microbiome diversity and local inflammatory response; and (3) correctly identify pathogens detected by conventional culture.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Thirty-seven of 90 ICU patients with suspected VAP had positive cultures. Patients with a positive culture had significant microbiome dysbiosis with reduced alpha diversity. However, gross compositional variance was not strongly associated with culture positivity (AUROCC range 0.66\u20130.71). Patients with a positive culture had a significantly higher relative abundance of pathogenic bacteria compared to those without [0.45 (IQR 0.10\u20130.84), 0.02 (IQR 0.004\u20130.09), respectively], and an increased interleukin (IL)-1\u03b2 was associated with reduced species evenness (<jats:italic>r<\/jats:italic><jats:sub>s<\/jats:sub>\u2009=\u2009\u2212\u20090.33, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01) and increased pathogenic bacteria presence (<jats:italic>r<\/jats:italic><jats:sub>s<\/jats:sub>\u2009=\u20090.28, <jats:italic>p<\/jats:italic>\u2009=\u20090.013). Untargeted 16s rRNA pathogen detection was limited by false positives, while the use of pathogen-specific relative abundance thresholds showed better diagnostic accuracy (AUROCC range 0.89\u20130.998).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Patients with positive BALF culture had increased dysbiosis and genus dominance. An increased caspase-1-dependent IL-1b expression was associated with a reduced species evenness and increased pathogenic bacterial presence, providing a possible causal link between microbiome dysbiosis and lung injury development in VAP. However, measures of diversity were an unreliable predictor of culture positivity and 16s sequencing used agnostically could not usefully identify pathogens; this could be overcome if pathogen-specific relative abundance thresholds are used.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13054-022-04068-z","type":"journal-article","created":{"date-parts":[[2022,7,6]],"date-time":"2022-07-06T17:03:11Z","timestamp":1657126991000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Composition and diversity analysis of the lung microbiome in patients with suspected ventilator-associated pneumonia"],"prefix":"10.1186","volume":"26","author":[{"given":"Dominic","family":"Fenn","sequence":"first","affiliation":[]},{"given":"Mahmoud I.","family":"Abdel-Aziz","sequence":"additional","affiliation":[]},{"given":"Pouline M. 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Since this study concerned the inclusion of patients lacking capacity, formal assent was sought at time of inclusion from a designated consultee who was independent of the study. For patients that regained capacity, deferred written consent was obtained. If patients did not regain capacity, the General Data Protection Regulation (GDPR) states that the obtained data could be used for research purposes without consent. BreathDx was registered by the UK Clinical Research Network (ID no. 19086). The study methods have previously been published [].","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Dr Dominic Fenn has nothing to disclose. Dr Abdel-Aziz has nothing to disclose. Dr Pouline M. P. van Oort has nothing to disclose. Dr Paul Brinkman has nothing to disclose. Dr Waqar M. Ahmed has nothing to disclose. Dr Timothy Felton has nothing to disclose. Dr Antonio Artigas reports grants, personal fees and other from Grifols, grants from Fisher and Paykel, personal fees and other from Aerogen, other from Novartis, outside the submitted work. Dr Pedro P\u00f3voa reports personal fees from MSD, personal fees from Gilead, outside the submitted work. Dr Ignacio Martin-Loeches has nothing to disclose. Dr Marcus J. Schultz has nothing to disclose. Dr Paul Dark has nothing to disclose. Dr Stephen J. Fowler has nothing to disclose. Dr Lieuwe D.J. Bos reports grants from the Dutch lung foundation (Young investigator grant), grants from the Dutch lung foundation and Health Holland (Public\u2013Private Partnership grant), grants from the Dutch lung foundation (Dirkje Postma Award), grants from IMI COVID-19 initiative, grants from Amsterdam UMC fellowship, outside the submitted work. On behalf of the authors, I can confirm that there is no conflict of interest and that the manuscript has not been published elsewhere or under consideration by another journal. All the authors have approved the manuscript and agree with its submission to Critical Care.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"203"}}