{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T01:38:59Z","timestamp":1793151539945,"version":"4.5.0"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T00:00:00Z","timestamp":1672876800000},"content-version":"vor","delay-in-days":4,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Halloran Family Foundation"},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["RC2 DK118619"],"award-info":[{"award-number":["RC2 DK118619"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,1,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Primary sclerosing cholangitis (PSC) is a complex bile duct disorder. Its etiology is incompletely understood, but environmental chemicals likely contribute to risk. Patients with PSC have an altered bile metabolome, which may be influenced by environmental chemicals. This novel study utilized state-of-the-art high-resolution mass spectrometry (HRMS) with bile samples to provide the first characterization of environmental chemicals and metabolomics (collectively, the exposome) in PSC patients located in the United States of America (USA) (n\u2009=\u200924) and Norway (n\u2009=\u200930). First, environmental chemical- and metabolome-wide association studies were conducted to assess geographic-based similarities and differences in the bile of PSC patients. Nine environmental chemicals (false discovery rate, FDR\u2009&amp;lt;\u20090.20) and 3143 metabolic features (FDR\u2009&amp;lt;\u20090.05) differed by site. Next, pathway analysis was performed to identify metabolomic pathways that were similarly and differentially enriched by the site. Fifteen pathways were differentially enriched (P\u2009&amp;lt;\u2009.05) in the categories of amino acid, glycan, carbohydrate, energy, and vitamin\/cofactor metabolism. Finally, chemicals and pathways were integrated to derive exposure\u2013effect correlation networks by site. These networks demonstrate the shared and differential chemical\u2013metabolome associations by site and highlight important pathways that are likely relevant to PSC. The USA patients demonstrated higher environmental chemical bile content and increased associations between chemicals and metabolic pathways than those in Norway. Polychlorinated biphenyl (PCB)-118 and PCB-101 were identified as chemicals of interest for additional investigation in PSC given broad associations with metabolomic pathways in both the USA and Norway patients. Associated pathways include glycan degradation pathways, which play a key role in microbiome regulation and thus may be implicated in PSC pathophysiology.<\/jats:p>","DOI":"10.1093\/exposome\/osac011","type":"journal-article","created":{"date-parts":[[2023,1,8]],"date-time":"2023-01-08T03:22:38Z","timestamp":1673148158000},"source":"Crossref","is-referenced-by-count":6,"title":["Environmental chemicals and endogenous metabolites in bile of USA and Norway patients with primary sclerosing cholangitis"],"prefix":"10.1093","volume":"3","author":[{"given":"Caroline W","family":"Grant","sequence":"first","affiliation":[{"name":"Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic , Rochester, MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian D","family":"Juran","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, College of Medicine, Mayo Clinic , Rochester, MN, 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of Pulmonary, Allergy, Critical Care and Sleep Medicine, Emory University , GA, USA , Atlanta"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3353-0844","authenticated-orcid":false,"given":"Young-Mi","family":"Go","sequence":"additional","affiliation":[{"name":"Clinical Biomarkers Laboratory, Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Emory University , GA, USA , Atlanta"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dean P","family":"Jones","sequence":"additional","affiliation":[{"name":"Clinical Biomarkers Laboratory, Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Emory University , GA, USA , Atlanta"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas I","family":"Walker","sequence":"additional","affiliation":[{"name":"Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai , New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8984-1284","authenticated-orcid":false,"given":"Gary W","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Environmental Health Sciences, Columbia University Mailman School of Public Health , New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trine","family":"Folseraas","sequence":"additional","affiliation":[{"name":"Research Institute for Internal Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital Rikshospitalet and University of Oslo , Oslo, Norway"},{"name":"Norwegian PSC Research Center, Department of Transplantation Medicine, Division of Surgery, Inflammatory Medicine and Transplantation, Oslo University Hospital Rikshospitalet , Oslo, Norway"},{"name":"Institute of Clinical Medicine, Faculty of Medicine, University of Oslo , Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom H","family":"Karlsen","sequence":"additional","affiliation":[{"name":"Research Institute for Internal Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital Rikshospitalet and University of Oslo , Oslo, Norway"},{"name":"Norwegian PSC Research Center, Department of Transplantation Medicine, Division of Surgery, Inflammatory Medicine and Transplantation, Oslo University Hospital Rikshospitalet , Oslo, Norway"},{"name":"Institute of Clinical Medicine, Faculty of Medicine, University of Oslo , Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas F","family":"LaRusso","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, College of Medicine, Mayo Clinic , Rochester, MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory 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