{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:38:01Z","timestamp":1785418681345,"version":"3.56.0"},"posted":{"date-parts":[[2026,6,2]]},"group-title":"Addiction Medicine","reference-count":95,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T00:00:00Z","timestamp":1780358400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.medrxiv.org\/about\/FAQ#license"}],"funder":[{"award":["5T32AA007290-42"],"award-info":[{"award-number":["5T32AA007290-42"]}],"id":[{"id":"https:\/\/ror.org\/02jzrsm59","id-type":"ROR","asserted-by":"publisher"}]},{"award":["5P50AA027055-05 5380"],"award-info":[{"award-number":["5P50AA027055-05 5380"]}],"id":[{"id":"https:\/\/ror.org\/02jzrsm59","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,6,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  The gut microbiome has been implicated in alcohol use disorder (AUD), but its relationship to drinking intensity and treatment response remains poorly understood. We conducted a longitudinal multi-omics analysis of stool samples collected at baseline and endpoint (after 12 weeks) from 122 participants enrolled in a double-blind, placebo-controlled trial of dutasteride for AUD. Gut microbiome composition was characterized using 16S rRNA gene sequencing, and fecal metabolites were measured by LC-MS\u2013based metabolomics. At baseline, drinking intensity was associated with increasingly lower microbial richness. Genera in the class\n                  <jats:italic>Clostridia<\/jats:italic>\n                  emerged as key microbial hubs associated with drinking intensity in an age- and sex-dependent manner. Drinking intensity promoted co-enrichment of [\n                  <jats:italic>Ruminococcus<\/jats:italic>\n                  ]\n                  <jats:italic>gnavus<\/jats:italic>\n                  group and [\n                  <jats:italic>Clostridium<\/jats:italic>\n                  ]\n                  <jats:italic>inocuum<\/jats:italic>\n                  group with amino acid catabolites, as well as the co-depletion of diverse\n                  <jats:italic>Clostridia<\/jats:italic>\n                  taxa and lipid metabolites. Dutasteride treatment and drinking reduction had minimal impact on gut microbiome composition. Random forest models integrating baseline clinical, microbiome, and metabolome data improved the classification of clinically meaningful drinking reduction compared to models using clinical data alone. These findings show that a coupled baseline gut microbiome-metabolome signature is associated with drinking intensity and future treatment response in AUD, highlighting the potential for multi-omics integration to inform precision treatment approaches.\n                <\/jats:p>","DOI":"10.64898\/2026.05.26.26354041","type":"posted-content","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T05:05:13Z","timestamp":1780463113000},"source":"Crossref","is-referenced-by-count":0,"title":["Baseline Gut Microbiome-Metabolome Signatures Are Associated with Drinking Severity and Reduction Following Dutasteride Treatment in Alcohol Use Disorder"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4877-9450","authenticated-orcid":false,"given":"L.R.","family":"Dedon","sequence":"first","affiliation":[{"name":"Alcohol Research Center, Department of Psychiatry, UConn School of Medicine, Farmington, CT 06030"},{"name":"Department of Medicine, UConn School of Medicine, Farmington, CT 06030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-6232-5562","authenticated-orcid":false,"given":"D.J.","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Medicine, UConn School of Medicine, Farmington, CT 06030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Q.","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Computer Science and Engineering, University of Connecticut, Storrs, CT 06269"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4513-4817","authenticated-orcid":false,"given":"H.","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Medicine, UConn School of Medicine, Farmington, CT 06030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Chi","sequence":"additional","affiliation":[{"name":"Arizona Metabolomics Laboratory, College of Health Solutions, Arizona State University, Phoenix, AZ 85004"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Li","sequence":"additional","affiliation":[{"name":"Arizona Metabolomics Laboratory, College of Health Solutions, Arizona State University, Phoenix, AZ 85004"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7598-5022","authenticated-orcid":false,"given":"H.","family":"Gu","sequence":"additional","affiliation":[{"name":"Arizona Metabolomics Laboratory, College of Health Solutions, Arizona State University, Phoenix, AZ 85004"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Tennen","sequence":"additional","affiliation":[{"name":"Alcohol Research Center, Department of Psychiatry, UConn School of Medicine, Farmington, CT 06030"},{"name":"Department of Public Health Sciences, UConn School of Medicine, Farmington, CT 06030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3616-0431","authenticated-orcid":false,"given":"J.M.","family":"Covault","sequence":"additional","affiliation":[{"name":"Alcohol Research Center, Department of Psychiatry, UConn School of Medicine, Farmington, CT 06030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6528-7039","authenticated-orcid":false,"given":"Y.","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Medicine, UConn School of Medicine, Farmington, CT 06030"},{"name":"Center for Addiction Science and Innovation, University of Connecticut, Storrs, CT 06269"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026060511053567000_2026.05.26.26354041v1.1","doi-asserted-by":"publisher","DOI":"10.1097\/ADM.0000000000001609"},{"key":"2026060511053567000_2026.05.26.26354041v1.2","unstructured":"Substance Abuse and Mental Health Services Administration. 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