Gut microbiota from patients with COVID-19 cause alterations in mice that resemble post-COVID symptoms

Gut microbiota from patients with COVID-19 cause alterations in mice that resemble post-COVID symptoms | 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 microbiota from patients with COVID-19 cause alterations in mice that resemble post-COVID symptoms Viviani Mendes de Almeida, Daiane F Engel, Mayra Fernanda Ricci, and 28 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-1756189/v2 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 05 Sep, 2023 Read the published version in Gut Microbes → Version 2 posted You are reading this latest preprint version Show more versions Abstract Long-term sequelae after Coronavirus disease (COVID)-19 are frequent and of major concern. SARS-CoV-2 infection affects the host's gut microbiota, which is linked with disease severity in patients with COVID-19. We report here that the gut microbiota of post-COVID subjects had a remarkable predominance of Enterobacteriaceae strains with antibiotic-resistance phenotype compared to healthy controls. Additionally, short-chain fatty acids (SCFA) levels were reduced in their feces. Fecal transplant from post-COVID subjects to germ-free mice led to lung inflammation and worst outcomes during pulmonary infection by multidrug-resistant Klebsiella pneumoniae. Transplanted mice also had poorer cognitive performance. Overall, we show prolonged impacts of SARS-CoV-2 infection in the gut microbiota that persist after subjects have cleared the virus. Together, these data demonstrate that the gut microbiota can directly contribute to post-COVID sequelae, suggesting that it may be a potential therapeutic target. COVID-19 SARS-CoV-2 Post-COVID Microbiota Inflammation Antimicrobial-resistance Full Text Additional Declarations No competing interests reported. Supplementary Files Figure1figuresupplement1.tif Figure supplement 1. Workflow and flowchart for the collection and analysis of post-COVID and control human samples, and analysis of resistant Enterobacteriaceae species in human fecal samples. (A) Analysis of feeding habits sociodemographic, antibiotics use (at least 4 months before the application of sample collection), and clinical parameters of 59 control and 72 post-COVID subjects. Fresh feces were collected and subjected to SARS-CoV-2 quantification by RT-qPCR, 16S rRNA sequencing, SCFA’s measurements, cultivating fecal microbiota, and antimicrobial susceptibility tests. (B) Flowchart of the human samples. (C) Descriptive analysis of percentage of resistant Enterobacteriaceae species (N=131). Figure1figuresupplement1.tif Figure supplement 1. Workflow and flowchart for the collection and analysis of post-COVID and control human samples, and analysis of resistant Enterobacteriaceae species in human fecal samples. (A) Analysis of feeding habits sociodemographic, antibiotics use (at least 4 months before the application of sample collection), and clinical parameters of 59 control and 72 post-COVID subjects. Fresh feces were collected and subjected to SARS-CoV-2 quantification by RT-qPCR, 16S rRNA sequencing, SCFA’s measurements, cultivating fecal microbiota, and antimicrobial susceptibility tests. (B) Flowchart of the human samples. (C) Descriptive analysis of percentage of resistant Enterobacteriaceae species (N=131). Cite Share Download PDF Status: Published Journal Publication published 05 Sep, 2023 Read the published version in Gut Microbes → Version 2 posted You are reading this latest preprint version Show more versions 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-1756189","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":115630937,"identity":"067c0645-1075-4495-a588-96725b3a0bca","order_by":0,"name":"Viviani Mendes de Almeida","email":"","orcid":"","institution":"Laboratory of Microbiota and Immunomodulation - Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais-UFMG, Belo Horizonte, MG, Brazil","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Viviani","middleName":"Mendes","lastName":"de Almeida","suffix":""},{"id":115630938,"identity":"3352830b-2bb5-4497-97be-e61613ae0bfd","order_by":1,"name":"Daiane F Engel","email":"","orcid":"","institution":"Department of Clinical Analysis, School of Pharmacy, Universidade Federal de Ouro Preto -UFOP, Ouro Preto, MG, Brazil","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Daiane","middleName":"F","lastName":"Engel","suffix":""},{"id":115630939,"identity":"57dc9436-a9ac-4cec-9d6e-1bb270b3fb6c","order_by":2,"name":"Mayra Fernanda Ricci","email":"","orcid":"","institution":"Laboratory of Microbiota and Immunomodulation - Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais-UFMG, Belo Horizonte, MG, Brazil","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Mayra","middleName":"Fernanda","lastName":"Ricci","suffix":""},{"id":115630940,"identity":"2436e2c5-c7dd-45e5-bacf-f1df26f86b30","order_by":3,"name":"Clênio Silva Cruz","email":"","orcid":"","institution":"Laboratory of Microbiota and Immunomodulation - Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais-UFMG, Belo Horizonte, MG, Brazil","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Clênio","middleName":"Silva","lastName":"Cruz","suffix":""},{"id":115630941,"identity":"3c59a339-87e2-4498-9ac3-accb8dc61aac","order_by":4,"name":"Icaro Santos Lopes","email":"","orcid":"","institution":"Laboratory of Virus Bioinformatics - Department of Biological Science, Center of Biotechnology and Genetics, Universidade Estadual de Santa Cruz-UESC, Ilhéus, BA, Brazil.","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Icaro","middleName":"Santos","lastName":"Lopes","suffix":""},{"id":115630942,"identity":"99c5e174-81ea-4325-a240-4dc89a99b6ca","order_by":5,"name":"Daniele Almeida Alves","email":"","orcid":"","institution":"Laboratory of RNA interference and antiviral immunity - Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais-UFMG, Belo Horizonte, MG, Braz","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Daniele","middleName":"Almeida","lastName":"Alves","suffix":""},{"id":115630943,"identity":"633dd8f1-63b3-4c03-8a3a-23eb8ed9ee37","order_by":6,"name":"Mirna d’ Auriol","email":"","orcid":"","institution":"Laboratory of Toxicology - Departament of Clinical and Toxicological Analysis, Faculty of Pharmacy, Universidade Federal de Minas Gerais-UFMG, Belo Horizonte, MG, Brazil","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Mirna","middleName":"d’","lastName":"Auriol","suffix":""},{"id":115630944,"identity":"a1ccf8af-98e8-4691-9eaa-e7c729cf8518","order_by":7,"name":"João Magalhães","email":"","orcid":"","institution":"Laboratory of Microbiota and Immunomodulation - Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais-UFMG, Belo Horizonte, MG, Brazil","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"João","middleName":"","lastName":"Magalhães","suffix":""},{"id":115630945,"identity":"32ffd217-8680-4748-a6ea-91597571c302","order_by":8,"name":"Giuliana S. 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(\u003cstrong\u003eA\u003c/strong\u003e) Analysis of feeding habits sociodemographic, antibiotics use (at least 4 months before the application of sample collection), and clinical parameters of 59 control and 72 post-COVID subjects. Fresh feces were collected and subjected to SARS-CoV-2 quantification by RT-qPCR, 16S rRNA sequencing, SCFA’s measurements, cultivating fecal microbiota, and antimicrobial susceptibility tests. (\u003cstrong\u003eB\u003c/strong\u003e) Flowchart of the human samples. (\u003cstrong\u003eC\u003c/strong\u003e) Descriptive analysis of percentage of resistant \u003cem\u003eEnterobacteriaceae\u003c/em\u003e species (N=131).\u003c/p\u003e","description":"","filename":"Figure1figuresupplement1.tif","url":"https://assets-eu.researchsquare.com/files/rs-1756189/v2/a577aaf8ae511f66ab87c119.tif"},{"id":35670718,"identity":"f434caa3-1838-45be-a833-cb142c5e7e4a","added_by":"auto","created_at":"2023-04-12 20:33:07","extension":"tif","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":66922664,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFigure supplement 1. \u003c/strong\u003eWorkflow and flowchart for the collection and analysis of post-COVID and control human samples, and analysis of resistant \u003cem\u003eEnterobacteriaceae\u003c/em\u003e species in human fecal samples. (\u003cstrong\u003eA\u003c/strong\u003e) Analysis of feeding habits sociodemographic, antibiotics use (at least 4 months before the application of sample collection), and clinical parameters of 59 control and 72 post-COVID subjects. Fresh feces were collected and subjected to SARS-CoV-2 quantification by RT-qPCR, 16S rRNA sequencing, SCFA’s measurements, cultivating fecal microbiota, and antimicrobial susceptibility tests. (\u003cstrong\u003eB\u003c/strong\u003e) Flowchart of the human samples. (\u003cstrong\u003eC\u003c/strong\u003e) Descriptive analysis of percentage of resistant \u003cem\u003eEnterobacteriaceae\u003c/em\u003e species (N=131).\u003c/p\u003e","description":"","filename":"Figure1figuresupplement1.tif","url":"https://assets-eu.researchsquare.com/files/rs-1756189/v2/a12e5504fd74bbee541d4352.tif"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eGut microbiota from patients with COVID-19 cause alterations in mice that resemble post-COVID symptoms\u003c/p\u003e","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"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":"COVID-19, SARS-CoV-2, Post-COVID, Microbiota, Inflammation, Antimicrobial-resistance","lastPublishedDoi":"10.21203/rs.3.rs-1756189/v2","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-1756189/v2","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eLong-term sequelae after Coronavirus disease (COVID)-19 are frequent and of major concern. SARS-CoV-2 infection affects the host's gut microbiota, which is linked with disease severity in patients with COVID-19. We report here that the gut microbiota of post-COVID subjects had a remarkable predominance of \u003cem\u003eEnterobacteriaceae \u003c/em\u003estrains with antibiotic-resistance phenotype compared to healthy controls. Additionally, short-chain fatty acids (SCFA) levels were reduced in their feces. Fecal transplant from post-COVID subjects to germ-free mice led to lung inflammation and worst outcomes during pulmonary infection by multidrug-resistant \u003cem\u003eKlebsiella pneumoniae. \u003c/em\u003eTransplanted mice also had poorer cognitive performance. Overall,\u003cstrong\u003e \u003c/strong\u003ewe show prolonged impacts of SARS-CoV-2 infection in the gut microbiota that persist after subjects have cleared the virus. Together, these data demonstrate that the gut microbiota can directly contribute to post-COVID sequelae, suggesting that it may be a potential therapeutic target.\u003c/p\u003e","manuscriptTitle":"Gut microbiota from patients with COVID-19 cause alterations in mice that resemble post-COVID symptoms","msid":"","msnumber":"","nonDraftVersions":[{"code":2,"date":"2023-04-12 20:25:01","doi":"10.21203/rs.3.rs-1756189/v2","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}},{"code":1,"date":"2022-06-22 16:44:19","doi":"10.21203/rs.3.rs-1756189/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":"94e8c4e9-3186-4ccd-bd08-6af04ef98564","owner":[],"postedDate":"April 12th, 2023","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[{"value":"featured","date":"2022-07-01 20:31:06"}],"updatedAt":"2024-05-28T18:35:23+00:00","versionOfRecord":{"articleIdentity":"rs-1756189","link":"https://doi.org/10.1080/19490976.2023.2249146","journal":{"identity":"gut-microbes","isVorOnly":true,"title":"Gut Microbes"},"publishedOn":"2023-09-05 18:35:23","publishedOnDateReadable":"September 5th, 2023"},"versionCreatedAt":"2023-04-12 20:25:01","video":"","vorDoi":"10.1080/19490976.2023.2249146","vorDoiUrl":"https://doi.org/10.1080/19490976.2023.2249146","workflowStages":[]},"version":"v2","identity":"rs-1756189","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-1756189","identity":"rs-1756189","version":["v2"]},"buildId":"WrCJVZZCHTDjtuVLN7oU0","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}