An Ifnar1 allele impairs the colonization of gut bacteria and promotes tuberculosis

An Ifnar1 allele impairs the colonization of gut bacteria and promotes tuberculosis | 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 Article An Ifnar1 allele impairs the colonization of gut bacteria and promotes tuberculosis Lingming Chen, Guoliang Zhang, Guobao Li, Wei Wang, Zhen-Huang Ge, and 18 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-847439/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 14 Mar, 2022 Read the published version in Nature Metabolism → Version 1 posted You are reading this latest preprint version Abstract Both host genetics and gut microbiome have important effects on human health, yet how host genetics regulates gut bacteria and further determines disease susceptibility remains unclear. Here, we find that gut microbiome pattern of active tuberculosis (TB) patients is characterized by a reduction of core species found across healthy controls, particularly Akkermansia muciniphila ( A. muciniphila ). Oral treatments of A. muciniphila or palmitoleic acid, an A. muciniphila -derived metabolite, strongly inhibit TB infection through epigenetically inhibiting TNF-α. We use three independent cohorts comprising 6512 individuals and identify that single-nucleotide polymorphism rs2257167 “G” allele of type I interferon (IFN-I) receptor 1 ( Ifnar1 ) contributes to stronger IFN-I signaling, impaired colonization and abundance of A. muciniphila , reduced production of palmitoleic acid, higher TNF-α, and much severer TB disease in humans and transgenic mice. Thus, host genetics are critical in modulating structure and functions of gut microbiome and gut microbial metabolites, which further determines disease susceptibility. General Microbiology Infectious Diseases tuberculosis host genetics gut bacteria disease susceptibility Full Text Additional Declarations There is NO Competing Interest. Supplementary Files STROBEchecklistcohort.pdf STROBE_checklist nreditorialpolicychecklist.pdf editorial-policy-checklist nrreportingsummary.pdf reporting-summary AblankversionoftheInformedConsentofGuangzhouShenzhenandFoshancohorts.pdf A blank version of the Informed Consent TheethicalboardapprovalsofGuangzhouShenzhenandFoshancohorts.pdf The ethical board approvals Cite Share Download PDF Status: Published Journal Publication published 14 Mar, 2022 Read the published version in Nature Metabolism → 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-847439","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":49354271,"identity":"66a7653e-787c-451a-9ce0-56b5a3db6a2a","order_by":0,"name":"Lingming Chen","email":"","orcid":"","institution":"Department of Microbiology, Zhongshan School of Medicine, Key Laboratory for Tropical Diseases Control of the Ministry of Education, Sun Yat-sen University, Guangzhou 510080, 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\u003ci\u003eIfnar1\u003c/i\u003e allele impairs the colonization of gut bacteria \r\nand promotes tuberculosis","fulltext":[{"header":"Full Text","content":"This preprint is available for \u003ca href='/article/rs-847439/latest.pdf' target='_blank'\u003edownload as a PDF\u003c/a\u003e."}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"nature-portfolio","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"","title":"Nature Portfolio","twitterHandle":"","acdcEnabled":false,"dfaEnabled":false,"editorialSystem":"ejp","reportingPortfolio":"","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"tuberculosis, host genetics, gut bacteria, disease susceptibility ","lastPublishedDoi":"10.21203/rs.3.rs-847439/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-847439/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Both host genetics and gut microbiome have important effects on human health, yet how host genetics regulates gut bacteria and further determines disease susceptibility remains unclear. Here, we find that gut microbiome pattern of active tuberculosis (TB) patients is characterized by a reduction of core species found across healthy controls, particularly \u003ci\u003eAkkermansia muciniphila\u003c/i\u003e (\u003ci\u003eA. muciniphila\u003c/i\u003e). Oral treatments of \u003ci\u003eA. muciniphila\u003c/i\u003e or palmitoleic acid, an \u003ci\u003eA. muciniphila\u003c/i\u003e-derived metabolite, strongly inhibit TB infection through epigenetically inhibiting TNF-α. We use three independent cohorts comprising 6512 individuals and identify that single-nucleotide polymorphism rs2257167 “G” allele of type I interferon (IFN-I) receptor 1 (\u003ci\u003eIfnar1\u003c/i\u003e) contributes to stronger IFN-I signaling, impaired colonization and abundance of \u003ci\u003eA. muciniphila\u003c/i\u003e, reduced production of palmitoleic acid, higher TNF-α, and much severer TB disease in humans and transgenic mice. Thus, host genetics are critical in modulating structure and functions of gut microbiome and gut microbial metabolites, which further determines disease susceptibility.","manuscriptTitle":"An Ifnar1 allele impairs the colonization of gut bacteria \nand promotes tuberculosis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2021-09-02 19:00:50","doi":"10.21203/rs.3.rs-847439/v1","editorialEvents":[],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"nature-metabolism","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"natmetab","sideBox":"Learn more about [Nature Metabolism](http://www.nature.com/natmetab/)","snPcode":"","submissionUrl":"","title":"Nature Metabolism","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature Research","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"618fc6af-2160-4347-884f-500c596ca5a0","owner":[],"postedDate":"September 2nd, 2021","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":6917873,"name":"General Microbiology"},{"id":6917874,"name":"Infectious Diseases"}],"tags":[],"updatedAt":"2022-03-28T20:04:57+00:00","versionOfRecord":{"articleIdentity":"rs-847439","link":"https://doi.org/10.1038/s42255-022-00547-3","journal":{"identity":"nature-metabolism","isVorOnly":false,"title":"Nature Metabolism"},"publishedOn":"2022-03-14 04:00:00","publishedOnDateReadable":"March 14th, 2022"},"versionCreatedAt":"2021-09-02 19:00:50","video":"","vorDoi":"10.1038/s42255-022-00547-3","vorDoiUrl":"https://doi.org/10.1038/s42255-022-00547-3","workflowStages":[]},"version":"v1","identity":"rs-847439","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-847439","identity":"rs-847439","version":["v1"]},"buildId":"cBFmMYwuxLRRLfASyISRj","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}