Gut–Lung Crosstalk: Correlating Gut Microbial Composition with Pulmonary Disorders in COPD Murine models

Gut–Lung Crosstalk: Correlating Gut Microbial Composition with Pulmonary Disorders in COPD Murine models | 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 Gut–Lung Crosstalk: Correlating Gut Microbial Composition with Pulmonary Disorders in COPD Murine models Rui WEI, Runhua HOU, Zili ZHANG, Rui CHEN, Qin LIAO, Chunyun ZHANG, and 8 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7949688/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 Background Chronic Obstructive Pulmonary Disease (COPD) is a systemic inflammatory disease with significant extrapulmonary manifestations. The gut-lung axis has emerged as a crucial area of research, but the specific alterations in the gut microbiota and their correlation with COPD pathophysiology remain largely unknown. Methods We established a murine model of COPD by exposing SD rats to chronic cigarette smoke (CS) and further induced COPD exacerbation (ECOPD) using PM2.5 and LPS. We characterized the gut microbiota using 16S rRNA gene sequencing and performed comprehensive bioinformatics analysis, including alpha and beta diversity, compositional analysis, differential species analysis (LEfSe), and functional prediction (KEGG). We also assessed lung function, lung histopathology, and inflammatory markers to validate the COPD model and investigate correlations with gut microbiota alterations. Results The COPD murine model successfully recapitulated key features of the disease, including airflow limitation, lung inflammation, and alveolar destruction. We observed significant decreases in gut microbial richness and diversity in COPD animals except the LPS-induced ECOPD ones, characterized by alpha diversity analysis. A general shift was observed in microbial taxa for COPD animals compared to controls, specifically an increase in Erysipelotrichaceae and Bifidobacteriaceae , and a decrease in Lactobacillaceae and Lachnospiraceae , and the exacerbation triggers (PM2.5 and LPS) further modify the gut microbiota structure. Importantly, we found significant correlations between gut microbial diversity and lung function, as well as between specific bacterial genera and pulmonary inflammatory markers. Functional prediction analysis indicated significant alterations in metabolic pathways within the gut microbiota of COPD animals. Conclusion Our study demonstrates that a murine model of COPD exhibits significant gut microbiota dysbiosis, which is closely correlated with key pulmonary pathophysiological indicators. These findings provide novel evidence for the involvement of the gut-lung axis in COPD and suggest that the gut microbiota may serve as a potential diagnostic biomarker and therapeutic target for this debilitating disease. Chronic Obstructive Pulmonary Disease (COPD) Gut microbiota Gut-lung axis Dysbiosis Full Text Additional Declarations No competing interests reported. Supplementary Files 20251022graphicalAbstract.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. 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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-7949688","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":547109866,"identity":"cf7904ea-181b-49bb-a16a-81845ed10187","order_by":0,"name":"Rui WEI","email":"","orcid":"","institution":"The Fifth Affiliated Hospital of Guangzhou Medical University","correspondingAuthor":false,"prefix":"","firstName":"Rui","middleName":"","lastName":"WEI","suffix":""},{"id":547109867,"identity":"3e5b4307-de73-49ae-9256-8cf25e1e05ba","order_by":1,"name":"Runhua HOU","email":"","orcid":"","institution":"The Fifth Affiliated Hospital of Guangzhou 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models","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"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},"keywords":"Chronic Obstructive Pulmonary Disease (COPD), Gut microbiota; Gut-lung axis, Dysbiosis","lastPublishedDoi":"10.21203/rs.3.rs-7949688/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7949688/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eChronic Obstructive Pulmonary Disease (COPD) is a systemic inflammatory disease with significant extrapulmonary manifestations. The gut-lung axis has emerged as a crucial area of research, but the specific alterations in the gut microbiota and their correlation with COPD pathophysiology remain largely unknown.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eWe established a murine model of COPD by exposing SD rats to chronic cigarette smoke (CS) and further induced COPD exacerbation (ECOPD) using PM2.5 and LPS. We characterized the gut microbiota using 16S rRNA gene sequencing and performed comprehensive bioinformatics analysis, including alpha and beta diversity, compositional analysis, differential species analysis (LEfSe), and functional prediction (KEGG). We also assessed lung function, lung histopathology, and inflammatory markers to validate the COPD model and investigate correlations with gut microbiota alterations.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eThe COPD murine model successfully recapitulated key features of the disease, including airflow limitation, lung inflammation, and alveolar destruction. We observed significant decreases in gut microbial richness and diversity in COPD animals except the LPS-induced ECOPD ones, characterized by alpha diversity analysis. A general shift was observed in microbial taxa for COPD animals compared to controls, specifically an increase in \u003cem\u003eErysipelotrichaceae\u003c/em\u003e and \u003cem\u003eBifidobacteriaceae\u003c/em\u003e, and a decrease in \u003cem\u003eLactobacillaceae\u003c/em\u003e and \u003cem\u003eLachnospiraceae\u003c/em\u003e, and the exacerbation triggers (PM2.5 and LPS) further modify the gut microbiota structure. Importantly, we found significant correlations between gut microbial diversity and lung function, as well as between specific bacterial genera and pulmonary inflammatory markers. Functional prediction analysis indicated significant alterations in metabolic pathways within the gut microbiota of COPD animals.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eOur study demonstrates that a murine model of COPD exhibits significant gut microbiota dysbiosis, which is closely correlated with key pulmonary pathophysiological indicators. These findings provide novel evidence for the involvement of the gut-lung axis in COPD and suggest that the gut microbiota may serve as a potential diagnostic biomarker and therapeutic target for this debilitating disease.\u003c/p\u003e","manuscriptTitle":"Gut–Lung Crosstalk: Correlating Gut Microbial Composition with Pulmonary Disorders in COPD Murine models","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-24 16:24:55","doi":"10.21203/rs.3.rs-7949688/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":"49599f78-7e43-486d-9942-8c30465ac1a9","owner":[],"postedDate":"November 24th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-12-02T10:38:14+00:00","versionOfRecord":[],"versionCreatedAt":"2025-11-24 16:24:55","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7949688","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7949688","identity":"rs-7949688","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}