{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:10:51Z","timestamp":1785413451862,"version":"3.56.0"},"posted":{"date-parts":[[2026,3,30]]},"group-title":"Microbiology","reference-count":82,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T00:00:00Z","timestamp":1774828800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,3,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  The human gut microbiome influences treatment outcomes, but whether microbiome signatures of drug response generalize across cohorts remains unclear. Here, we perform a multi-cohort analysis (3 cohorts, N=100 patients) to determine whether cross-cohort microbial signatures are associated with methotrexate (MTX) response in new-onset rheumatoid arthritis (RA) patients. Pre-treatment gut microbiome community structure and function differed by future MTX response status, with MTX-nonresponders (MTX-NR) showing\n                  <jats:italic>Bacteroides caccae<\/jats:italic>\n                  depletion and\n                  <jats:italic>Ruminococcus bromii<\/jats:italic>\n                  enrichment. Multiple microbial functions were depleted in MTX-NR, including nucleotide metabolism, one-carbon pool by folate, and histidine metabolism. Notably, candidate MTX-degrading genes were enriched in MTX-NR. Microbiome functional profiles outperformed clinical metrics in predicting future MTX response. These results show that consistent microbiome signatures are associated with MTX response across different RA cohorts and pave the way for microbiome-based precision medicine in newly diagnosed RA patients.\n                <\/jats:p>","DOI":"10.64898\/2026.03.30.715090","type":"posted-content","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T04:10:24Z","timestamp":1774930224000},"source":"Crossref","is-referenced-by-count":0,"title":["Multi-cohort Analysis Reveals Microbiome Signatures Associated with Drug Response in New-Onset Rheumatoid Arthritis"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7902-3357","authenticated-orcid":false,"given":"Rahul L.","family":"Bodkhe","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Rheumatology, University of California, San Francisco, San Francisco, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6292-6947","authenticated-orcid":false,"given":"Rebecca B.","family":"Blank","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, NYU Grossman School of Medicine, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8672-6317","authenticated-orcid":false,"given":"Kai R.","family":"Trepka","sequence":"additional","affiliation":[{"name":"Department of Microbiology & Immunology, University of California, San Francisco, San Francisco, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego A.","family":"Orellana","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Rheumatology, University of California, San Francisco, San Francisco, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1072-6994","authenticated-orcid":false,"given":"Jose U.","family":"Scher","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, NYU Grossman School of Medicine, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0888-2875","authenticated-orcid":false,"given":"Peter J.","family":"Turnbaugh","sequence":"additional","affiliation":[{"name":"Department of Microbiology & Immunology, University of California, San Francisco, San Francisco, CA, USA"},{"name":"Biohub-San Francisco, San Francisco, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1123-4668","authenticated-orcid":false,"given":"Renuka R.","family":"Nayak","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Rheumatology, University of California, San Francisco, San Francisco, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026040209350598000_2026.03.30.715090v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-024-01068-4"},{"key":"2026040209350598000_2026.03.30.715090v1.2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro.2016.17"},{"key":"2026040209350598000_2026.03.30.715090v1.3","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20180448"},{"key":"2026040209350598000_2026.03.30.715090v1.4","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1002\/art.41622","article-title":"The pretreatment gut microbiome is associated with lack of response to methotrexate in new-onset rheumatoid arthritis","volume":"73","year":"2021","journal-title":"Arthritis Rheumatol"},{"key":"2026040209350598000_2026.03.30.715090v1.5","doi-asserted-by":"crossref","unstructured":"Villa Soto, V.S. , et al. 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