{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T11:42:24Z","timestamp":1790768544308,"version":"4.1.0"},"reference-count":50,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","license":[{"start":{"date-parts":[[2021,11,26]],"date-time":"2021-11-26T00:00:00Z","timestamp":1637884800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatol Commun"],"published-print":{"date-parts":[[2022,5]]},"abstract":"<jats:p>\n                    Progress in development of prognostic and therapeutic options for the rare cholestatic liver diseases, primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC), is hampered by limited knowledge of their pathogeneses. In particular, the potential role of hepatotoxic and\/or metabolism\u2010altering environmental chemicals in the pathogenesis of these diseases remains relatively unstudied. Moreover, the extent to which metabolic pathways are altered due to ongoing cholestasis and subsequent liver damage or possibly influenced by hepatotoxic chemicals is poorly understood. In this study, we applied a comprehensive exposomics\u2010metabolomics approach to uncover potential pathogenic contributors to PSC and PBC. We used untargeted high\u2010resolution mass spectrometry to characterize a wide range of exogenous chemicals and endogenous metabolites in plasma and tested them for association with disease. Exposome\u2010wide association studies (EWAS) identified environmental chemicals, including pesticides, additives and persistent pollutants, that were associated with PSC and\/or PBC, suggesting potential roles for these compounds in disease pathogenesis. Metabolome\u2010wide association studies (MWAS) found disease\u2010associated alterations to amino acid, eicosanoid, lipid, co\u2010factor, nucleotide, mitochondrial and microbial metabolic pathways, many of which were shared between PSC and PBC. Notably, this analysis implicates a potential role of the 5\u2010lipoxygenase pathway in the pathogenesis of these diseases. Finally, EWAS \u00d7 MWAS network analysis uncovered linkages between environmental agents and disrupted metabolic pathways that provide insight into potential mechanisms for PSC and PBC.\n                    <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic>\n                    This study establishes combined exposomics\u2010metabolomics as a generalizable approach to identify potentially pathogenic environmental agents and enumerate metabolic alterations that may impact PSC and PBC, providing a foundation for diagnostic and therapeutic strategies.\n                  <\/jats:p>","DOI":"10.1002\/hep4.1871","type":"journal-article","created":{"date-parts":[[2021,11,26]],"date-time":"2021-11-26T06:54:38Z","timestamp":1637909678000},"page":"965-979","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":32,"title":["High\u2010Resolution Exposomics and Metabolomics Reveals Specific Associations in Cholestatic Liver Diseases"],"prefix":"10.1097","volume":"6","author":[{"given":"Douglas I.","family":"Walker","sequence":"first","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"}]},{"given":"Brian D.","family":"Juran","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology,Mayo Clinic,Rochester,MN,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela C.","family":"Cheung","sequence":"additional","affiliation":[{"name":"Gastroenterology and Hepatology,Department of Medicine,The Ottawa Hospital,Ottawa,ON,Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik M.","family":"Schlicht","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology,Mayo Clinic,Rochester,MN,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongliang","family":"Liang","sequence":"additional","affiliation":[{"name":"Clinical Biomarkers Laboratory,Division of Pulmonary,Allergy,Critical Care and Sleep Medicine,Emory University,Atlanta,GA,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan","family":"Niedzwiecki","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"}]},{"given":"Nicholas F.","family":"LaRusso","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology,Mayo Clinic,Rochester,MN,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory J.","family":"Gores","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology,Mayo Clinic,Rochester,MN,USA"}],"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,Atlanta,GA,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0437-681X","authenticated-orcid":false,"given":"Konstantinos N.","family":"Lazaridis","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology,Mayo 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