Gut Microbiota Mediates Prenatal METH Exposure-Induced Anxiety- and Depression-Like Behaviors by Modulating the Wnt Signaling Pathway

Gut Microbiota Mediates Prenatal METH Exposure-Induced Anxiety- and Depression-Like Behaviors by Modulating the Wnt Signaling Pathway | 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 Mediates Prenatal METH Exposure-Induced Anxiety- and Depression-Like Behaviors by Modulating the Wnt Signaling Pathway Jia-Hao Li, Jia-Li Liu, Xiu-Wen Li, Jian-Zheng Yang, Yi Liu, Clare Hsu, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5224306/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: Prenatal methamphetamine (METH) exposure poses a significant threat to offspring health, including anxiety and depression-like behaviors. This study investigated the neurotoxicity of prenatal METH exposure in offspring and explored the underlying mechanisms. Results: Our results showed that prenatal METH exposure induced anxiety- and depression-like behaviors in offspring, accompanied by increased hippocampal inflammation and decreased hippocampal neurogenesis. Importantly, offspring exposed to prenatal METH exhibited gut microbiota dysbiosis, characterized by a reduced abundance of beneficial bacteria and an increased abundance of pro-inflammatory bacteria. To assess the involvement of the gut microbiota, we conducted cross-fostering and inulin supplementation experiments. Cross-fostering with control dams partially reversed METH-induced behavioral deficits, suggesting a role for maternal microbiota transmission. Inulin supplementation, both during pregnancy and in offspring, effectively remodeled the gut microbiota composition and alleviated anxiety and depression-like behaviors. This effect was associated with reduced hippocampal inflammation and increased hippocampal neurogenesis, potentially mediated by activation of the canonical Wnt signaling pathway. Conclusions: Gut microbiota mediates prenatal METH exposure-induced anxiety- and depression-like behaviors by modulating the WNT signaling pathway. This study provides evidence for the critical role of the gut microbiota in mediating the neurodevelopmental consequences of prenatal METH exposure, and highlights the potential of inulin supplementation as a promising therapeutic strategy. Prenatal methamphetamine exposure Offspring Anxiety- and depression-like behaviors Gut microbiota Inulin Full Text Additional Declarations No competing interests reported. Supplementary Files Supplementalmaterials.docx 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. 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-5224306","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":364941270,"identity":"4d4645c7-63e2-47fd-9bda-2929bd05830f","order_by":0,"name":"Jia-Hao Li","email":"","orcid":"","institution":"Southern Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jia-Hao","middleName":"","lastName":"Li","suffix":""},{"id":364941271,"identity":"bb69526a-60a3-46b9-9ed7-3cf3e3a47718","order_by":1,"name":"Jia-Li Liu","email":"","orcid":"","institution":"Southern Medical 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10:08:37","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5224306/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5224306/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":68374479,"identity":"91840990-dc3f-40d8-ac00-fbe2dadfcc00","added_by":"auto","created_at":"2024-11-06 15:01:23","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3346351,"visible":true,"origin":"","legend":"","description":"","filename":"RevisedManuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5224306/v1_covered_df8502ff-d6f8-4f80-92b4-bca9ccf5ca19.pdf"},{"id":66645035,"identity":"25130af9-f859-4e21-9a2e-69c054a6f224","added_by":"auto","created_at":"2024-10-15 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Inulin","lastPublishedDoi":"10.21203/rs.3.rs-5224306/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5224306/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003ePrenatal methamphetamine (METH) exposure poses a significant threat to offspring health, including anxiety and depression-like behaviors. This study investigated the neurotoxicity of prenatal METH exposure in offspring and explored the underlying mechanisms.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eOur results showed that prenatal METH exposure induced anxiety- and depression-like behaviors in offspring, accompanied by increased hippocampal inflammation and decreased hippocampal neurogenesis. Importantly, offspring exposed to prenatal METH exhibited gut microbiota dysbiosis, characterized by a reduced abundance of beneficial bacteria and an increased abundance of pro-inflammatory bacteria. To assess the involvement of the gut microbiota, we conducted cross-fostering and inulin supplementation experiments. Cross-fostering with control dams partially reversed METH-induced behavioral deficits, suggesting a role for maternal microbiota transmission. 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This study provides evidence for the critical role of the gut microbiota in mediating the neurodevelopmental consequences of prenatal METH exposure, and highlights the potential of inulin supplementation as a promising therapeutic strategy.\u003c/p\u003e","manuscriptTitle":"Gut Microbiota Mediates Prenatal METH Exposure-Induced Anxiety- and Depression-Like Behaviors by Modulating the Wnt Signaling Pathway","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-10-15 06:47:09","doi":"10.21203/rs.3.rs-5224306/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":"0600332b-e007-49f7-b375-7f7bd4cd9511","owner":[],"postedDate":"October 15th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-11-06T14:53:11+00:00","versionOfRecord":[],"versionCreatedAt":"2024-10-15 06:47:09","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5224306","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5224306","identity":"rs-5224306","version":["v1"]},"buildId":"FbvkV6FR0MCFSLy54lSbu","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}