The Effect of Probiotics Supplementation on Mental Health Outcomes Among Children and Adolescents: A Systematic Review and Meta-Analysis of randomized controlled trials

The Effect of Probiotics Supplementation on Mental Health Outcomes Among Children and Adolescents: A Systematic Review and Meta-Analysis of randomized controlled trials | 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 Systematic Review The Effect of Probiotics Supplementation on Mental Health Outcomes Among Children and Adolescents: A Systematic Review and Meta-Analysis of randomized controlled trials Mulat Mossie Menalu, Amare Deribew This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8788605/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 15 You are reading this latest preprint version Abstract Background Interest is growing in microbiota-targeted approaches to support mental health in children and adolescents. Probiotics may influence brain function through the microbiota–gut–brain axis, but evidence in pediatric populations remains limited, and prior reviews often include non-RCT data, weakening conclusions. So, this study aimed to evaluate the effects of probiotic supplementation on mental health outcomes in children and adolescents using randomized controlled trials only. Methods This systematic review and meta-analysis followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. Comprehensive searches of PubMed/MEDLINE, Embase, Cochrane CENTRAL, and ClinicalTrials.gov. Eligible studies included participants aged ≤ 18 years, compared probiotics with placebo or non-probiotic controls, and reported validated mental health outcomes. Risk of bias was assessed using the Cochrane Risk of bias 2 tool. Meta-analysis was conducted using standardized mean differences with 95% confidence intervals. Results Of 51 records identified, seven trials met inclusion criteria, focusing on attention deficit hyperactivity disorder (three studies), autism spectrum disorder (two studies), and depression or anxiety (two studies). Overall risk of bias was rated as having some concerns. Three trials (n = 215) were sufficiently comparable for meta-analysis. Probiotic supplementation was associated with a statistically significant improvement in mental health outcomes (pooled mean difference − 0.4; 95% CI − 0.69 to − 0.01), indicating a moderate reduction in symptom severity across anxiety, depressive symptoms, attention deficit hyperactivity disorder -related difficulties, stress, and behavioral problems. Conclusions Probiotic supplementation has beneficial effects on mental health outcomes in children and adolescents. However, the limited number of randomized controlled trials warrant cautious interpretation. Larger, well-designed trials with standardized outcomes are needed to clarify clinical relevance and long-term effects. probiotics mental health children and adolescents randomized controlled trials gut–brain axis Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 13 Apr, 2026 Reviews received at journal 12 Apr, 2026 Reviews received at journal 07 Apr, 2026 Reviewers agreed at journal 02 Apr, 2026 Reviewers agreed at journal 02 Apr, 2026 Reviewers agreed at journal 14 Mar, 2026 Reviews received at journal 14 Mar, 2026 Reviews received at journal 09 Mar, 2026 Reviewers agreed at journal 07 Mar, 2026 Reviewers agreed at journal 05 Mar, 2026 Reviewers invited by journal 05 Mar, 2026 Editor invited by journal 10 Feb, 2026 Editor assigned by journal 06 Feb, 2026 Submission checks completed at journal 06 Feb, 2026 First submitted to journal 04 Feb, 2026 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. 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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-8788605","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Systematic Review","associatedPublications":[],"authors":[{"id":603162928,"identity":"fe1758c4-b3c8-47ca-82b2-c8d18dc8c0c2","order_by":0,"name":"Mulat Mossie Menalu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA3ElEQVRIiWNgGAWjYFAC5gYozcD4AEjx8BHWwtjAcACihdkApIWNeC0MDGwSYJKQBt0ZiY2fP+bY2Mu3Mx+r/JpjJ8PGwPzw0Q08WsxuJDZLHNyWlrjhMFvabdltyUCHsRkb5+DX0gDUcjjBgJnH7LbkNmagFh42aQJamn8AtdjLN/N/K5bcVk+UljaQLYwNh3nYGD9uO0yEljMP2yzOQvxiLM247TgPGzMhvxxPPnyjchswxPoPP/z4c1u1PT9788PH+LSgAGYeMEmschBg/EGK6lEwCkbBKBgxAAA4KUkkpFKmPAAAAABJRU5ErkJggg==","orcid":"","institution":"Bahir Dar university","correspondingAuthor":true,"prefix":"","firstName":"Mulat","middleName":"Mossie","lastName":"Menalu","suffix":""},{"id":603162929,"identity":"e5cabf83-f22b-4190-a5e6-a44d2a1a3dcd","order_by":1,"name":"Amare Deribew","email":"","orcid":"","institution":"Bahir Dar university","correspondingAuthor":false,"prefix":"","firstName":"Amare","middleName":"","lastName":"Deribew","suffix":""}],"badges":[],"createdAt":"2026-02-04 16:09:01","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8788605/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8788605/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":104406388,"identity":"9c7457a0-e552-480e-90c5-f5ee32b31095","added_by":"auto","created_at":"2026-03-11 12:25:37","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":835161,"visible":true,"origin":"","legend":"","description":"","filename":"ProbioticsandmentaldisorderSystematicreviewandmetaanalysis5.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8788605/v1_covered_524b480c-74a4-4532-b0de-27c8edd3381e.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"The Effect of Probiotics Supplementation on Mental Health Outcomes Among Children and Adolescents: A Systematic Review and Meta-Analysis of randomized controlled trials","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"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":"bmc-psychiatry","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bpsy","sideBox":"Learn more about [BMC Psychiatry](http://bmcpsychiatry.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bpsy/default.aspx","title":"BMC Psychiatry","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"probiotics, mental health, children and adolescents, randomized controlled trials, gut–brain axis","lastPublishedDoi":"10.21203/rs.3.rs-8788605/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8788605/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eInterest is growing in microbiota-targeted approaches to support mental health in children and adolescents. Probiotics may influence brain function through the microbiota\u0026ndash;gut\u0026ndash;brain axis, but evidence in pediatric populations remains limited, and prior reviews often include non-RCT data, weakening conclusions. So, this study aimed to evaluate the effects of probiotic supplementation on mental health outcomes in children and adolescents using randomized controlled trials only.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis systematic review and meta-analysis followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. Comprehensive searches of PubMed/MEDLINE, Embase, Cochrane CENTRAL, and ClinicalTrials.gov. Eligible studies included participants aged\u0026thinsp;\u0026le;\u0026thinsp;18 years, compared probiotics with placebo or non-probiotic controls, and reported validated mental health outcomes. Risk of bias was assessed using the Cochrane Risk of bias 2 tool. Meta-analysis was conducted using standardized mean differences with 95% confidence intervals.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eOf 51 records identified, seven trials met inclusion criteria, focusing on attention deficit hyperactivity disorder (three studies), autism spectrum disorder (two studies), and depression or anxiety (two studies). Overall risk of bias was rated as having some concerns. Three trials (n\u0026thinsp;=\u0026thinsp;215) were sufficiently comparable for meta-analysis. Probiotic supplementation was associated with a statistically significant improvement in mental health outcomes (pooled mean difference\u0026thinsp;\u0026minus;\u0026thinsp;0.4; 95% CI\u0026thinsp;\u0026minus;\u0026thinsp;0.69 to \u0026minus;\u0026thinsp;0.01), indicating a moderate reduction in symptom severity across anxiety, depressive symptoms, attention deficit hyperactivity disorder -related difficulties, stress, and behavioral problems.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eProbiotic supplementation has beneficial effects on mental health outcomes in children and adolescents. However, the limited number of randomized controlled trials warrant cautious interpretation. Larger, well-designed trials with standardized outcomes are needed to clarify clinical relevance and long-term effects.\u003c/p\u003e","manuscriptTitle":"The Effect of Probiotics Supplementation on Mental Health Outcomes Among Children and Adolescents: A Systematic Review and Meta-Analysis of randomized controlled trials","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-10 22:18:31","doi":"10.21203/rs.3.rs-8788605/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-04-13T06:53:51+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-12T08:24:32+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-07T18:49:09+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"287760528224118533999512643176176957791","date":"2026-04-02T09:20:05+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"23647887876980874450794756262911280365","date":"2026-04-02T07:17:23+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"140748954955131059747141754286031370786","date":"2026-03-14T11:00:41+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-14T05:33:58+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-09T13:28:58+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"36175511655248693001066162407598084679","date":"2026-03-07T14:13:05+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"64437024728867421684226385807171200973","date":"2026-03-05T13:27:56+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-03-05T12:53:13+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-02-10T11:33:47+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-02-06T10:09:58+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-02-06T10:04:30+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Psychiatry","date":"2026-02-04T15:50:46+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-psychiatry","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bpsy","sideBox":"Learn more about [BMC Psychiatry](http://bmcpsychiatry.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bpsy/default.aspx","title":"BMC Psychiatry","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"7d16b372-6ed8-4f73-91ff-64ca9a8690ef","owner":[],"postedDate":"March 10th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-04-21T08:40:24+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-10 22:18:31","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8788605","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8788605","identity":"rs-8788605","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}