The gut microbiota modulates the rate of ALS progression

The gut microbiota modulates the rate of ALS progression | 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 The gut microbiota modulates the rate of ALS progression Raphael Valdivia, Maria Emilia Panzetta, Katherine Mueller, Jason Arnold, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6370840/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease that can progress at varying rates; however, the factors influencing progression rates in ALS patients remain unknown. In this study, we report distinct microbiome and metabolomic signatures associated with ALS progression rates. Rapid progression rates were transferable to a genetic mouse model of ALS following a fecal microbiota transplant (FMT) from patients exhibiting rapid disease progression. By focusing on microbial and metabolic markers shared between the FMT donors and mouse recipients, we identified Phocaeicola vulgatus as a microbial biomarker for slow progression. Additionally, we found strain-level differences in P. vulgatus among ALS patients and isolated a strain that partially alleviated disease in mice that received microbiota linked with rapid progression. Identifying microbiota that accelerates ALS progression, along with strains of P. vulgatus and correlated metabolites that mitigate such accelerated diseases, reveals new avenues for potential therapeutic interventions. Biological sciences/Physiology/Metabolism/Metabolomics Biological sciences/Microbiology/Microbial communities/Microbiome Full Text Additional Declarations Yes there is potential Competing Interest. R.H.V. is a founder of Bloom Science (San Diego, CA). M.E.P. received funding support from Bloom Science. Supplementary Files ST01Extendeddatatable1.xlsx Extended data Table 1 ST02Extendeddatatable2.xlsx Extended data Table 2 ST03Extendeddatatable3.xlsx Extended data Table 3 ST04Extendeddatatable4.xlsx Extended data Table 4 ST05Extendeddatatable5.xlsx Extended data Table 5 ST06Extendeddatatable6.xlsx Extended data Table 6 Cite Share Download PDF Status: Under Review 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-6370840","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":443214329,"identity":"c7977a36-b69d-43c3-a79f-f2e84eac3e9b","order_by":0,"name":"Raphael Valdivia","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABDUlEQVRIiWNgGAWjYHACNiC2AGLmBokEBgkGfoYEZpAwYwN+LRJgNWAtkg0kaQFxDQ4Q0GLefvbYgx8VEgwGxw823njYZiFvfDzH2OADg43shgPYtcicyUs37DkD1HImsdkisU3CcNuZN8aJMxjSjHFpkWDIMZPgbQN5Aag+4YwE47YbOcaHeRgOJ+LUwv/GTPLvP6CW/odgLfabZwC1/GH4j1uLRI6ZNC/Q4/wSIFsqJBI3SOQYJzMwHMCj5V2atMwxCR5+iYfNFkAtyTPOPCs27DFINp6J02G5xyTf1NjIsfEnH7z5w6DOtr89ebPEjwo72T4cWhgYeJBIBDDApRyb4lEwCkbBKBgF6AAA3ohZ5FjSJPgAAAAASUVORK5CYII=","orcid":"https://orcid.org/0000-0003-0961-073X","institution":"Duke University Medical Center","correspondingAuthor":true,"prefix":"","firstName":"Raphael","middleName":"","lastName":"Valdivia","suffix":""},{"id":443214330,"identity":"8f2f6f5f-aa13-429e-98f0-e04735d480fd","order_by":1,"name":"Maria Emilia Panzetta","email":"","orcid":"https://orcid.org/0000-0003-3616-8713","institution":"Duke","correspondingAuthor":false,"prefix":"","firstName":"Maria","middleName":"Emilia","lastName":"Panzetta","suffix":""},{"id":443214331,"identity":"186f1e3a-f12f-4ba5-92e6-3f0adac988f7","order_by":2,"name":"Katherine Mueller","email":"","orcid":"https://orcid.org/0000-0001-5179-7484","institution":"Duke University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Katherine","middleName":"","lastName":"Mueller","suffix":""},{"id":443214332,"identity":"c8550f89-580e-4849-8457-2f6162a6d14d","order_by":3,"name":"Jason Arnold","email":"","orcid":"","institution":"Duke University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Jason","middleName":"","lastName":"Arnold","suffix":""},{"id":443214333,"identity":"0d9967dc-c662-45e1-850a-a159eaca50e3","order_by":4,"name":"Raquel Perry","email":"","orcid":"https://orcid.org/0000-0001-6150-020X","institution":"Duke University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Raquel","middleName":"","lastName":"Perry","suffix":""},{"id":443214334,"identity":"8844e5b0-7a0f-456b-a081-f834c4e5192f","order_by":5,"name":"Richard Bedlack","email":"","orcid":"","institution":"Duke University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Richard","middleName":"","lastName":"Bedlack","suffix":""}],"badges":[],"createdAt":"2025-04-03 16:01:19","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6370840/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6370840/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":97895210,"identity":"5460fe40-64b1-4349-a459-32beaba44ee0","added_by":"auto","created_at":"2025-12-10 15:33:49","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":4309762,"visible":true,"origin":"","legend":"Article File","description":"","filename":"PanzettaetalThegutmicrobiotamodulatestherateofALSprogression.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6370840/v1_covered_122746ba-12dd-4d03-afd5-cb064b52f360.pdf"},{"id":80784296,"identity":"684fe5e5-0e7e-4035-8844-27da46a9e321","added_by":"auto","created_at":"2025-04-17 05:34:53","extension":"xlsx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":57077,"visible":true,"origin":"","legend":"Extended data Table 1","description":"","filename":"ST01Extendeddatatable1.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-6370840/v1/5db5a41c8c7f057bf0bf16da.xlsx"},{"id":80784300,"identity":"b3b5567d-6e24-4f71-90ac-2b6228c3525d","added_by":"auto","created_at":"2025-04-17 05:34:54","extension":"xlsx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":673513,"visible":true,"origin":"","legend":"\u003cp\u003eExtended data Table 2\u003c/p\u003e","description":"","filename":"ST02Extendeddatatable2.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-6370840/v1/79308f6b939e58a624a35a27.xlsx"},{"id":80784297,"identity":"eba5babb-6e2b-4cce-9a14-99cd9e9a8a57","added_by":"auto","created_at":"2025-04-17 05:34:53","extension":"xlsx","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":600883,"visible":true,"origin":"","legend":"\u003cp\u003eExtended data Table 3\u003c/p\u003e","description":"","filename":"ST03Extendeddatatable3.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-6370840/v1/e8094c87607fa0d11595d848.xlsx"},{"id":80784299,"identity":"a4807566-077e-4453-9c04-43928eb7b177","added_by":"auto","created_at":"2025-04-17 05:34:54","extension":"xlsx","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":347369,"visible":true,"origin":"","legend":"\u003cp\u003eExtended data Table 4\u003c/p\u003e","description":"","filename":"ST04Extendeddatatable4.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-6370840/v1/a15d1439de7b1907cc9607c9.xlsx"},{"id":80784303,"identity":"eddf041d-4225-495b-8a93-3acba564185a","added_by":"auto","created_at":"2025-04-17 05:34:54","extension":"xlsx","order_by":5,"title":"","display":"","copyAsset":false,"role":"supplement","size":2761551,"visible":true,"origin":"","legend":"Extended data Table 5","description":"","filename":"ST05Extendeddatatable5.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-6370840/v1/3ea86dd67717b91916a96b9a.xlsx"},{"id":80784301,"identity":"a204a0b6-c0c0-476a-a7c1-b192680f2b07","added_by":"auto","created_at":"2025-04-17 05:34:54","extension":"xlsx","order_by":6,"title":"","display":"","copyAsset":false,"role":"supplement","size":362773,"visible":true,"origin":"","legend":"Extended data Table 6","description":"","filename":"ST06Extendeddatatable6.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-6370840/v1/28d96f392dcfb7eb7876e689.xlsx"}],"financialInterests":"\u003cb\u003eYes\u003c/b\u003e there is potential Competing Interest.\nR.H.V. is a founder of Bloom Science (San Diego, CA). M.E.P. received funding support from Bloom Science.","formattedTitle":"The gut microbiota modulates the rate of ALS progression","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"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":"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":"","lastPublishedDoi":"10.21203/rs.3.rs-6370840/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6370840/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease that can progress at varying rates; however, the factors influencing progression rates in ALS patients remain unknown. In this study, we report distinct microbiome and metabolomic signatures associated with ALS progression rates. Rapid progression rates were transferable to a genetic mouse model of ALS following a fecal microbiota transplant (FMT) from patients exhibiting rapid disease progression. By focusing on microbial and metabolic markers shared between the FMT donors and mouse recipients, we identified Phocaeicola vulgatus as a microbial biomarker for slow progression. Additionally, we found strain-level differences in P. vulgatus among ALS patients and isolated a strain that partially alleviated disease in mice that received microbiota linked with rapid progression. Identifying microbiota that accelerates ALS progression, along with strains of P. vulgatus and correlated metabolites that mitigate such accelerated diseases, reveals new avenues for potential therapeutic interventions.","manuscriptTitle":"The gut microbiota modulates the rate of ALS progression","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-04-17 05:34:49","doi":"10.21203/rs.3.rs-6370840/v1","editorialEvents":[],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"nature-microbiology","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"nmicrobiol","sideBox":"Learn more about [Nature Microbiology](http://www.nature.com/nmicrobiol/)","snPcode":"","submissionUrl":"","title":"Nature Microbiology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature Research","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"701c528e-0887-4a73-b9fd-7a7029378774","owner":[],"postedDate":"April 17th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":47186834,"name":"Biological sciences/Physiology/Metabolism/Metabolomics"},{"id":47186835,"name":"Biological sciences/Microbiology/Microbial communities/Microbiome"}],"tags":[],"updatedAt":"2026-02-18T16:01:30+00:00","versionOfRecord":[],"versionCreatedAt":"2025-04-17 05:34:49","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6370840","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6370840","identity":"rs-6370840","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}