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Am J Physiol Gastrointest Liver Physiol 293: G256-G263, 2007. First published April 5, 2007; doi:10.1152/ajpgi.00027.2007
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LIVER AND BILIARY TRACT

Human cecal bile acids: concentration and spectrum

James P. Hamilton,1 Guofeng Xie,1 Jean-Pierre Raufman,1 Susan Hogan,2 Terrance L. Griffin,3 Christine A. Packard,3 Dale A. Chatfield,3 Lee R. Hagey,4 Joseph H. Steinbach,4 and Alan F. Hofmann4

1Division of Gastroenterology and Hepatology, Department of Medicine, Veterans Affairs Maryland Health Care System and University of Maryland School of Medicine, Baltimore; 2Office of the Chief Medical Examiner, State of Maryland, Baltimore, Maryland; 3Department of Chemistry, San Diego State University, San Diego; and 4Division of Gastroenterology, Department of Medicine, University of California, San Diego, California

Submitted 12 January 2007 ; accepted in final form 26 March 2007

To obtain information on the concentration and spectrum of bile acids in human cecal content, samples were obtained from 19 persons who had died an unnatural death from causes such as trauma, homicide, suicide, or drug overdose. Bile acid concentration was measured via an enzymatic assay for 3{alpha}-hydroxy bile acids; bile acid classes were determined by electrospray ionization mass spectrometry and individual bile acids by gas chromatography mass spectrometry and liquid chromatography mass spectrometry. The 3{alpha}-hydroxy bile acid concentration (µmol bile acid/ml cecal content) was 0.4 ± 0.2 mM (mean ± SD); the total 3-hydroxy bile acid concentration was 0.6 ± 0.3 mM. The aqueous concentration of bile acids (supernatant after centrifugation) was identical, indicating that most bile acids were in solution. By liquid chromatography mass spectrometry, bile acids were mostly in unconjugated form (90 ± 9%, mean ± SD); sulfated, nonamidated bile acids were 7 ± 5%, and nonsulfated amidated bile acids (glycine or taurine conjugates) were 3 ± 7%. By gas chromatography mass spectrometry, 10 bile acids were identified: deoxycholic (34 ± 16%), lithocholic (26 ± 10%), and ursodeoxycholic (6 ± 9), as well as their primary bile acid precursors cholic (6 ± 9%) and chenodeoxycholic acid (7 ± 8%). In addition, 3beta-hydroxy derivatives of some or all of these bile acids were present and averaged 27 ± 18% of total bile acids, indicating that 3beta-hydroxy bile acids are normal constituents of cecal content. In the human cecum, deconjugation and dehydroxylation of bile acids are nearly complete, resulting in most bile acids being in unconjugated form at submicellar and subsecretory concentrations.

bile acid deconjugation; bile acid dehydroxylation; intestinal bile acids; mass spectrometry of bile acids



Address for reprint requests and correspondence regarding general aspects of the study: J.-P. Raufman, Univ. of Maryland School of Medicine, 22 S. Greene St., N3W62 Baltimore, MD 21201 (e-mail: jraufman{at}medicine.umaryland.edu). Address for correspondence regarding bile acid metabolism: A. F. Hofmann, Univ. of California, San Diego, San Diego, La Jolla, CA 92093-0813 (e-mail: ahofmann{at}ucsd.edu)




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