Gut microbiota metabolic reprogramming in metastatic prostatic cancer: prognostic value in patients under androgen receptor pathway inhibitors therapy.

Gut microbiota metabolic reprogramming in metastatic prostatic cancer: prognostic value in patients under androgen receptor pathway inhibitors therapy. | 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 Gut microbiota metabolic reprogramming in metastatic prostatic cancer: prognostic value in patients under androgen receptor pathway inhibitors therapy. Sonia María Pérez Castro, Manuel Carballo Quinta, Adrián Freire Rodríguez, and 9 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5837549/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 Metastatic prostate cancer (MPCa) is considered an aggressive condition. The objective was to elucidate the link between gut microbiota (GM) derived metabolites and disease progression in MPCa. Fecal microbiome shallow shotgun metagenomics of 15 patients with MPCa receiving ARPIs therapy were studied. A control group of 39 patients with untreated PCa was included. ARPIs-driven changes in the GM leading to functional redundancy in testosterone synthesis were observed. The GM could be contributing to epithelial–mesenchymal transition and MPCa progression by the increased synthesis of microbial-derived acetate. The feature-level analysis revealed that Bifidobacterium longum was enriched in the patients in aprogression stage (LinDA coefficient 5.7) whereas Sutterella wadsworthensis, Butyricimonas, Bilophila wadsworthia, Alistipesindistinctus, Bacteroides thetaiotaomicron and Intestinimonas were depleted (LinDA coefficient -7.2, -5.1, -4.4, -3.9, -3.9and -2.9, respectively). Bifidobacterium longum, Butyricimonas, Butyricimonas faecihominis, Bilophila sp. and Bacteroides thetaiotaomicron abundances were predictive of progression (AUC 0.88, 0.92, 0.88, 0.93 and 0.86, respectively, DESeq2; p <0.00001). A deeper understanding of the multifaceted roles of intestinal microorganisms at various stages of the disease would be of crucial importance to achieve an overall perspective of the individual prognosis of MPCa. Biological sciences/Cancer Biological sciences/Microbiology Health sciences/Urology Microbiome metastatic prostate cancer ARPIs progression prediction Bifidobacterium longum Full Text Additional Declarations No competing interests reported. Supplementary Files supplementarymaterial.zip 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-5837549","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":402716257,"identity":"a8b6eb17-046b-488c-affd-d15c72fb05fa","order_by":0,"name":"Sonia María Pérez 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cancer: prognostic value in patients under androgen receptor pathway inhibitors therapy.","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"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":"Microbiome, metastatic prostate cancer, ARPIs, progression, prediction, Bifidobacterium longum","lastPublishedDoi":"10.21203/rs.3.rs-5837549/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5837549/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Metastatic prostate cancer (MPCa) is considered an aggressive condition. The objective was to elucidate the link between gut microbiota (GM) derived metabolites and disease progression in MPCa. Fecal microbiome shallow shotgun metagenomics of 15 patients with MPCa receiving ARPIs therapy were studied. A control group of 39 patients with untreated PCa was included. ARPIs-driven changes in the GM leading to functional redundancy in testosterone synthesis were observed. The GM could be contributing to epithelial–mesenchymal transition and MPCa progression by the increased synthesis of microbial-derived acetate. The feature-level analysis revealed that Bifidobacterium longum was enriched in the patients in aprogression stage (LinDA coefficient 5.7) whereas Sutterella wadsworthensis, Butyricimonas, Bilophila wadsworthia, Alistipesindistinctus, Bacteroides thetaiotaomicron and Intestinimonas were depleted (LinDA coefficient -7.2, -5.1, -4.4, -3.9, -3.9and -2.9, respectively). Bifidobacterium longum, Butyricimonas, Butyricimonas faecihominis, Bilophila sp. and Bacteroides thetaiotaomicron abundances were predictive of progression (AUC 0.88, 0.92, 0.88, 0.93 and 0.86, respectively, DESeq2; p \u003c0.00001). A deeper understanding of the multifaceted roles of intestinal microorganisms at various stages of the disease would be of crucial importance to achieve an overall perspective of the individual prognosis of MPCa.","manuscriptTitle":"Gut microbiota metabolic reprogramming in metastatic prostatic cancer: prognostic value in patients under androgen receptor pathway inhibitors therapy.","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-01-17 03:02:06","doi":"10.21203/rs.3.rs-5837549/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":"5f3665e0-b047-43ac-91da-dc785a157212","owner":[],"postedDate":"January 17th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":42930639,"name":"Biological sciences/Cancer"},{"id":42930640,"name":"Biological sciences/Microbiology"},{"id":42930641,"name":"Health sciences/Urology"}],"tags":[],"updatedAt":"2025-12-29T14:24:22+00:00","versionOfRecord":[],"versionCreatedAt":"2025-01-17 03:02:06","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5837549","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5837549","identity":"rs-5837549","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}