title: Inflammatory bowel disease alters intestinal bile acid transporter expression.
abstract: The enterohepatic circulation of bile acids (BAs) critically depends on absorption of BA in the terminal ileum and colon, which can be affected by inflammatory bowel disease (IBD). Diarrhea in IBD is believed to result in part from BA malabsorption (BAM). We explored whether IBD alters mRNA expression of key intestinal BA transporters, BA detoxifying systems, and nuclear receptors that regulate BA transport and detoxification. Using real-time polymerase chain reaction, mucosal biopsy specimens from the terminal ileum in Crohn's disease (CD) patients and from the descending colon in ulcerative colitis (UC) patients were assessed for mRNA expression. Levels were compared with healthy controls. The main ileal BA uptake transporter, the apical sodium dependent bile acid transporter, was downregulated in active CD and UC and in CD in remission. Other significant changes such as repression of breast cancer-related protein and sulphotransferase 2A1 were seen only during active disease. In UC, pancolitis (but not exclusively left-sided colitis) was associated with altered expression of major BA transporters [multidrug resistance-associated protein 3 (MRP3), MRP4, multidrug resistance gene 1, organic solute transporter α/β] and nuclear receptors (pregnane X receptor, vitamin D receptor) in the descending colon. UC pancolitis leads to broad changes and CD ileitis to selective changes in intestinal BA transporter expression. Early medical manipulation of intestinal BA transporters may help prevent BAM.
authors: Laboratory of Experimental and Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Medicine (J.J., P.F., C.H., M.T.), Department of Paediatrics and Adolescent Medicine (J.J., A.C.H.), and Institute for Medical Informatics, Statistics and Documentation (A.A.), Medical University Graz, Graz, Austria; and Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria (M.T.) joerg.jahnel@medunigraz.at michael.trauner@meduniwien.ac.at.
authors: Jörg
authors: J
authors: Jahnel
authors: Laboratory of Experimental and Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Medicine (J.J., P.F., C.H., M.T.), Department of Paediatrics and Adolescent Medicine (J.J., A.C.H.), and Institute for Medical Informatics, Statistics and Documentation (A.A.), Medical University Graz, Graz, Austria; and Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria (M.T.).
authors: Peter
authors: P
authors: Fickert
authors: Laboratory of Experimental and Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Medicine (J.J., P.F., C.H., M.T.), Department of Paediatrics and Adolescent Medicine (J.J., A.C.H.), and Institute for Medical Informatics, Statistics and Documentation (A.A.), Medical University Graz, Graz, Austria; and Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria (M.T.).
authors: Almuthe C
authors: AC
authors: Hauer
authors: Laboratory of Experimental and Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Medicine (J.J., P.F., C.H., M.T.), Department of Paediatrics and Adolescent Medicine (J.J., A.C.H.), and Institute for Medical Informatics, Statistics and Documentation (A.A.), Medical University Graz, Graz, Austria; and Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria (M.T.).
authors: Christoph
authors: C
authors: Högenauer
authors: Laboratory of Experimental and Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Medicine (J.J., P.F., C.H., M.T.), Department of Paediatrics and Adolescent Medicine (J.J., A.C.H.), and Institute for Medical Informatics, Statistics and Documentation (A.A.), Medical University Graz, Graz, Austria; and Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria (M.T.).
authors: Alexander
authors: A
authors: Avian
authors: Laboratory of Experimental and Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Medicine (J.J., P.F., C.H., M.T.), Department of Paediatrics and Adolescent Medicine (J.J., A.C.H.), and Institute for Medical Informatics, Statistics and Documentation (A.A.), Medical University Graz, Graz, Austria; and Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria (M.T.).
authors: Michael
authors: M
authors: Trauner
mesh_terms: D000328:Adult; D001647:Bile Acids and Salts / Q000235:genetics / Q000378:metabolism*; D001706:Biopsy / Q000379:methods; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000235:genetics / Q000378:metabolism; D003106:Colon / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D006801:Humans; D007082:Ileum / Q000378:metabolism*; D015212:Inflammatory Bowel Diseases / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D029363:Organic Anion Transporters, Sodium-Dependent / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism; D027981:Symporters / Q000235:genetics / Q000378:metabolism*
chemical_list: D001647:Bile Acids and Salts; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D029363:Organic Anion Transporters, Sodium-Dependent; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D027981:Symporters; C037643:bile acid binding proteins; C071908:sodium-bile acid cotransporter