Brief Articles
Copyright ©2009 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. Jul 7, 2009; 15(25): 3134-3141
Published online Jul 7, 2009. doi: 10.3748/wjg.15.3134
Serum bile acid profiling reflects enterohepatic detoxification state and intestinal barrier function in inflammatory bowel disease
Carsten Gnewuch, Gerhard Liebisch, Thomas Langmann, Benjamin Dieplinger, Thomas Mueller, Meinhard Haltmayer, Hans Dieplinger, Alexandra Zahn, Wolfgang Stremmel, Gerhard Rogler, Gerd Schmitz
Carsten Gnewuch, Gerhard Liebisch, Thomas Langmann, Gerd Schmitz, Institute of Clinical Chemistry and Laboratory Medicine, Regensburg University Medical Center, Regensburg 93053, Germany
Thomas Langmann, Institute of Human Genetics, University of Regensburg, Regensburg 93053, Germany
Benjamin Dieplinger, Thomas Mueller, Meinhard Haltmayer, Department of Laboratory Medicine, Konventhospital Barmherzige Brueder Linz, Linz 4010, Austria
Hans Dieplinger, Division of Genetic Epidemiology, Department of Medical Genetics, Clinical and Molecular Pharmacology, Innsbruck Medical University, Innsbruck 6020, Austria
Alexandra Zahn, Wolfgang Stremmel, Department of Gastroenterology, University Hospital Heidelberg, Heidelberg 69120, Germany
Gerhard Rogler, Department of Internal Medicine I, Regensburg University Medical Center, Regensburg 93053, Germany
Author contributions: Gnewuch C, Langmann T and Rogler G contributed equally to this work by interpreting the results and writing the manuscript; Gnewuch C and Liebisch G contributed development of analytical methods and bile acid quantification; Gnewuch C performed bile acid and statistical analysis; Dieplinger B, Mueller T, Haltmayer M, Dieplinger H, Zahn A, Stremmel W and Rogler G contributed study material and patient data; Schmitz G initiated, conceived the study and organized funding.
Correspondence to: Gerd Schmitz, MD, Institute of Clinical Chemistry and Laboratory Medicine, Regensburg University Medical Center, Franz-Josef-Strauss-Allee 11, Regensburg 93053, Germany. gerd.schmitz@klinik.uni-regensburg.de
Telephone: +49-941-9446201
Fax: +49-941-9446202
Received: January 29, 2009
Revised: May 20, 2009
Accepted: May 27, 2009
Published online: July 7, 2009
Abstract

AIM: To determine free and conjugated serum bile acid (BA) levels in inflammatory bowel disease (IBD) subgroups with defined clinical manifestations.

METHODS: Comprehensive serum BA profiling was performed in 358 IBD patients and 310 healthy controls by liquid chromatography coupled to electrospray ionization tandem mass spectrometry.

RESULTS: Serum levels of hyodeoxycholic acid, the CYP3A4-mediated detoxification product of the secondary BA lithocholic acid (LCA), was increased significantly in Crohn’s disease (CD) and ulcerative colitis (UC), while most other serum BA species were decreased significantly. Total BA, total BA conjugate, and total BA glycoconjugate levels were decreased only in CD, whereas total unconjugated BA levels were decreased only in UC. In UC patients with hepatobiliary manifestations, the conjugated primary BAs glycocholic acid, taurocholic acid, and glycochenodeoxycholic acid were as significantly increased as the secondary BAs LCA, ursodeoxycholic acid, and tauroursodeoxycholic acid compared to UC patients without hepatobiliary manifestations. Finally, we found that in ileocecal resected CD patients, the unconjugated primary BAs, cholic acid and chenodeoxycholic acid, were increased significantly compared to controls and patients without surgical interventions.

CONCLUSION: Serum BA profiling in IBD patients that indicates impaired intestinal barrier function and increased detoxification is suitable for advanced diagnostic characterization and differentiation of IBD subgroups with defined clinical manifestations.

Keywords: Bile acids, Liquid chromatography, Tandem mass spectrometry, Inflammatory bowel disease, Crohn’s disease, Ulcerative colitis