{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T06:05:57Z","timestamp":1784700357118,"version":"3.55.0"},"reference-count":34,"publisher":"SAGE Publications","issue":"9","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"Clara E. and John H. Ware Jr. Foundation"},{"name":"Nancy Davis Race to Erase MS Young Investigator Award"},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01NS087226-01A1"],"award-info":[{"award-number":["R01NS087226-01A1"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01NS121928"],"award-info":[{"award-number":["R01NS121928"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R21NS126866"],"award-info":[{"award-number":["R21NS126866"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Water Cove Charitable Foundation"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Mult Scler"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Smokers with multiple sclerosis (MS) experience worse disease, yet underlying mechanisms remain unknown. Smoking disrupts bile acid and tryptophan metabolism in non-MS populations; both pathways involve host\u2013microbiome co-metabolism and have been linked to MS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>Determine whether smoking perturbs these metabolic pathways in MS and whether such alterations statistically mediate smoking\u2019s effect on MS severity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      We analyzed serum bile acid, tryptophan, and tobacco-related metabolites across four independent MS cohorts (\n                      <jats:italic toggle=\"yes\">N<\/jats:italic>\n                      \u2009=\u2009266) using discovery-replication analyses. Mixed-effects regression assessed replicating associations with current smoking and nicotine exposure. Mediation analyses tested if replicating metabolites were potential mediators between smoking and MS severity. Hypothesis-generating metagenomic analyses explored smoking-associated gut\u2013microbial shifts and metabolite correlations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Current smokers and nicotine-exposed MS subjects had reductions in bile acids and tryptophan metabolites, notably indolepropionate, a neuroprotective, anti-inflammatory gut\u2013microbial metabolite. Lower indolepropionate statistically mediated ~20% of smoking\u2019s adverse effect on MS severity. Metagenomic analyses identified potential smoking-enriched MS-linked taxa, and that indolepropionate broadly co-occurs with microbial networks (e.g.\n                      <jats:italic toggle=\"yes\">Lachnoclostridium<\/jats:italic>\n                      appeared inversely associated with indolepropionate in smokers with MS).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>Tobacco exposure disrupts host\u2013microbiome tryptophan and bile acid metabolism in persons with multiple sclerosis, with indolepropionate depletion partially mediating disease severity, highlighting a potential mechanistic pathway warranting further investigation in MS smokers.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13524585261454207","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T13:05:12Z","timestamp":1782911112000},"page":"972-984","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Tobacco smoking disrupts bile acid and tryptophan metabolism in multiple sclerosis"],"prefix":"10.1177","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0903-1359","authenticated-orcid":false,"given":"Farren BS","family":"Briggs","sequence":"first","affiliation":[{"name":"Department of Public Health Sciences, Miller School of Medicine, University of Miami, Miami, FL, USA; Department of Population and Quantitative Health Sciences, School of Medicine, Case Western Reserve University, Cleveland, OH, US"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jevin","family":"Litwiler","sequence":"additional","affiliation":[{"name":"School of Medicine, Case Western Reserve University, Cleveland, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Montini","sequence":"additional","affiliation":[{"name":"Center for Multiple Sclerosis and Autoimmune Neurology, Mayo Clinic, Rochester, MN, USA; Ann Romney Center for Neurologic Diseases, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahboubeh","family":"Fereidan Esfahani","sequence":"additional","affiliation":[{"name":"Department of Neurology, Dell Medical School, The University of Texas at Austin, Austin, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Sagen","sequence":"additional","affiliation":[{"name":"Center for Multiple Sclerosis and Autoimmune Neurology, Mayo Clinic, Rochester, MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1805-1733","authenticated-orcid":false,"given":"Jacob L","family":"McCauley","sequence":"additional","affiliation":[{"name":"John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavia","family":"Nelson","sequence":"additional","affiliation":[{"name":"Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Gregory","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurosurgery, Duke Molecular Physiology Institute, Duke University, Durham, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Brambilla","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, Miller School of Medicine, University of Miami, Miami, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika S","family":"Trapl","sequence":"additional","affiliation":[{"name":"Department of Population and Quantitative Health Sciences, School of Medicine, Case Western Reserve University, Cleveland, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica N","family":"Cooke Bailey","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, East Carolina University, Greenville, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luke A","family":"Schwerdtfeger","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Colorado State University, Fort Collins, CO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Cox","sequence":"additional","affiliation":[{"name":"Ann Romney Center for Neurologic Diseases, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Howard","family":"Weiner","sequence":"additional","affiliation":[{"name":"Ann Romney Center for Neurologic 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