Environmental chemicals and endogenous metabolites in bile of USA and Norway patients with primary sclerosing cholangitis.

Autor:	Grant CW; Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, USA., Juran BD; Division of Gastroenterology and Hepatology, College of Medicine, Mayo Clinic, Rochester, MN, USA., Ali AH; Division of Gastroenterology and Hepatology, College of Medicine, Mayo Clinic, Rochester, MN, USA.; Division of Gastroenterology and Hepatology, University of Missouri School of Medicine, One Hospital Drive, Columbia, MO, USA., Schlicht EM; Division of Gastroenterology and Hepatology, College of Medicine, Mayo Clinic, Rochester, MN, USA., Bianchi JK; Division of Gastroenterology and Hepatology, College of Medicine, Mayo Clinic, Rochester, MN, USA., Hu X; Clinical Biomarkers Laboratory, Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Emory University, GA, USA, Atlanta., Liang Y; Clinical Biomarkers Laboratory, Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Emory University, GA, USA, Atlanta., Jarrell Z; Clinical Biomarkers Laboratory, Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Emory University, GA, USA, Atlanta., Liu KH; Clinical Biomarkers Laboratory, Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Emory University, GA, USA, Atlanta., Go YM; Clinical Biomarkers Laboratory, Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Emory University, GA, USA, Atlanta., Jones DP; Clinical Biomarkers Laboratory, Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Emory University, GA, USA, Atlanta., Walker DI; Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Miller GW; Department of Environmental Health Sciences, Columbia University Mailman School of Public Health, New York, NY, USA., Folseraas T; Research Institute for Internal Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital Rikshospitalet and University of Oslo, Oslo, Norway.; Norwegian PSC Research Center, Department of Transplantation Medicine, Division of Surgery, Inflammatory Medicine and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway.; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway., Karlsen TH; Research Institute for Internal Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital Rikshospitalet and University of Oslo, Oslo, Norway.; Norwegian PSC Research Center, Department of Transplantation Medicine, Division of Surgery, Inflammatory Medicine and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway.; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway., LaRusso NF; Division of Gastroenterology and Hepatology, College of Medicine, Mayo Clinic, Rochester, MN, USA., Gores GJ; Division of Gastroenterology and Hepatology, College of Medicine, Mayo Clinic, Rochester, MN, USA., Athreya AP; Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, USA.; Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA., Lazaridis KN; Division of Gastroenterology and Hepatology, College of Medicine, Mayo Clinic, Rochester, MN, USA.
Jazyk:	angličtina
Zdroj:	Exposome [Exposome] 2023 Jan 05; Vol. 3 (1), pp. osac011. Date of Electronic Publication: 2023 Jan 05 (Print Publication: 2023).
DOI:	10.1093/exposome/osac011
Abstrakt:	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  = 24) and Norway ( n  = 30). 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 < 0.20) and 3143 metabolic features (FDR < 0.05) 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  < .05) in the categories of amino acid, glycan, carbohydrate, energy, and vitamin/cofactor metabolism. Finally, chemicals and pathways were integrated to derive exposure-effect correlation networks by site. These networks demonstrate the shared and differential chemical-metabolome 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. (© The Author(s) 2023. Published by Oxford University Press.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu