Mendelian Randomization Study on Lactobacillus salivarius, CD62L⁻ pDCs, and Luminal cerebral infarction Risk

Mendelian Randomization Study on Lactobacillus salivarius, CD62L⁻ pDCs, and Luminal cerebral infarction Risk | 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 Mendelian Randomization Study on Lactobacillus salivarius, CD62L⁻ pDCs, and Luminal cerebral infarction Risk Ying zi Gao, Yang Zhang, Chunliu Li, Lintao Dong, Zhen Zhang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6724483/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: Lacunar cerebral infarction (LCI) is a common subtype of ischemic stroke. Emerging evidence links the gut microbiota to cerebrovascular diseases through immune-mediated pathways, but causal relationships remain unclear. Methods: Genetic instruments for gut microbiota (n = 473 traits), immune cells (n = 731 traits), and LCI were obtained from large-scale GWAS datasets of European ancestry. Bidirectional MR and mediation MR analyses were conducted to evaluate directionality and immune mediation. Results: Genetically predicted Lactobacillus salivarius abundance was positively associated with LCI risk (OR = 2.123, 95% CI: 1.3045-3.4567, P =0.002/OR = 1.6427, 95% CI: 1.1379-2.3714, P =0.008). Among immune cell traits, CD62L⁻ plasmacytoid dendritic cells (pDCs) were identified as a significant mediator, showing a causal link with both L. salivarius and LCI. Mediation analysis revealed that 7.6% of the effect of L. salivarius on LCI risk was mediated through CD62L⁻ pDCs. Conclusions: This study provides genetic evidence that Lactobacillus salivarius may increase the risk of lacunar stroke via proinflammatory immune activation. These findings highlight the importance of gut–immune–brain interactions in stroke pathogenesis and suggest potential microbiota-targeted strategies for prevention. Neurology Luminal cerebral infarction Lactobacillus salivarius CD62L⁻ pDCs Intermediate Mendelian randomization Full Text Additional Declarations The authors declare no competing interests. Supplementary Files STROBEMRchecklistfillable.docx SupplementaryFigure.docx SupplementaryTable.xlsx 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. 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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-6724483","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":460409543,"identity":"8dab378a-4f42-40db-b94f-497188aeddb1","order_by":0,"name":"Ying zi Gao","email":"","orcid":"","institution":"Department of Neurology, Yantai Affiliated Hospital of Binzhou Medical University","correspondingAuthor":false,"prefix":"","firstName":"Ying","middleName":"zi","lastName":"Gao","suffix":""},{"id":460409544,"identity":"8d60cb6f-c08b-4d4a-aa4f-124473b58caa","order_by":1,"name":"Yang Zhang","email":"","orcid":"","institution":"The First Clinical 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Risk\u003c/strong\u003e\u003c/p\u003e","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"This research did not receive any specific grants from funding agencies in the public, commercial, or non-profit sectors.","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":"Luminal cerebral infarction, Lactobacillus salivarius, CD62L⁻ pDCs, Intermediate Mendelian randomization","lastPublishedDoi":"10.21203/rs.3.rs-6724483/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6724483/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBackground:\u003c/p\u003e\n\u003cp\u003eLacunar cerebral infarction (LCI) is a common subtype of ischemic stroke. Emerging evidence links the gut microbiota to cerebrovascular diseases through immune-mediated pathways, but causal relationships remain unclear.\u003c/p\u003e\n\u003cp\u003eMethods:\u003c/p\u003e\n\u003cp\u003eGenetic instruments for gut microbiota (n = 473 traits), immune cells (n = 731 traits), and LCI were obtained from large-scale GWAS datasets of European ancestry. Bidirectional MR and mediation MR analyses were conducted to evaluate directionality and immune mediation.\u003c/p\u003e\n\u003cp\u003eResults:\u003c/p\u003e\n\u003cp\u003eGenetically predicted Lactobacillus salivarius abundance was positively associated with LCI risk (OR = 2.123, 95% CI: 1.3045-3.4567, P =0.002/OR = 1.6427, 95% CI: 1.1379-2.3714, P =0.008). Among immune cell traits, CD62L⁻ plasmacytoid dendritic cells (pDCs) were identified as a significant mediator, showing a causal link with both L. salivarius and LCI. Mediation analysis revealed that 7.6% of the effect of L. salivarius on LCI risk was mediated through CD62L⁻ pDCs.\u003c/p\u003e\n\u003cp\u003eConclusions:\u003c/p\u003e\n\u003cp\u003eThis study provides genetic evidence that Lactobacillus salivarius may increase the risk of lacunar stroke via proinflammatory immune activation. These findings highlight the importance of gut–immune–brain interactions in stroke pathogenesis and suggest potential microbiota-targeted strategies for prevention.\u003c/p\u003e","manuscriptTitle":"Mendelian Randomization Study on Lactobacillus salivarius, CD62L⁻ pDCs, and Luminal cerebral infarction Risk","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-23 14:20:51","doi":"10.21203/rs.3.rs-6724483/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":"38272d6f-ce54-46e7-a222-30f243cbe59e","owner":[],"postedDate":"May 23rd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":48905820,"name":"Neurology"}],"tags":[],"updatedAt":"2025-05-23T14:20:51+00:00","versionOfRecord":[],"versionCreatedAt":"2025-05-23 14:20:51","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6724483","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6724483","identity":"rs-6724483","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}