Document Detail

Gut microbiota regulates bile acid metabolism by reducing the levels of tauro-beta-muricholic acid, a naturally occurring FXR antagonist.
MedLine Citation:
PMID:  23395169     Owner:  NLM     Status:  MEDLINE    
Bile acids are synthesized from cholesterol in the liver and further metabolized by the gut microbiota into secondary bile acids. Bile acid synthesis is under negative feedback control through activation of the nuclear receptor farnesoid X receptor (FXR) in the ileum and liver. Here we profiled the bile acid composition throughout the enterohepatic system in germ-free (GF) and conventionally raised (CONV-R) mice. We confirmed a dramatic reduction in muricholic acid, but not cholic acid, levels in CONV-R mice. Rederivation of Fxr-deficient mice as GF demonstrated that the gut microbiota regulated expression of fibroblast growth factor 15 in the ileum and cholesterol 7α-hydroxylase (CYP7A1) in the liver by FXR-dependent mechanisms. Importantly, we identified tauro-conjugated beta- and alpha-muricholic acids as FXR antagonists. These studies suggest that the gut microbiota not only regulates secondary bile acid metabolism but also inhibits bile acid synthesis in the liver by alleviating FXR inhibition in the ileum.
Sama I Sayin; Annika Wahlström; Jenny Felin; Sirkku Jäntti; Hanns-Ulrich Marschall; Krister Bamberg; Bo Angelin; Tuulia Hyötyläinen; Matej Orešič; Fredrik Bäckhed
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cell metabolism     Volume:  17     ISSN:  1932-7420     ISO Abbreviation:  Cell Metab.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-02-11     Completed Date:  2013-09-20     Revised Date:  2014-06-02    
Medline Journal Info:
Nlm Unique ID:  101233170     Medline TA:  Cell Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  225-35     Citation Subset:  IM    
Copyright Information:
Copyright © 2013 Elsevier Inc. All rights reserved.
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MeSH Terms
Anti-Bacterial Agents / pharmacology
Bile Acids and Salts / metabolism*
Cholesterol 7-alpha-Hydroxylase / genetics,  metabolism
Feedback, Physiological / drug effects
Fibroblast Growth Factors / genetics,  metabolism
Gastrointestinal Tract / drug effects,  microbiology*
Gene Expression Profiling
Gene Expression Regulation / drug effects
Ileum / drug effects,  metabolism
Liver / drug effects,  metabolism
Metagenome* / drug effects,  genetics
Models, Biological
Organ Specificity / drug effects,  genetics
Receptors, Cytoplasmic and Nuclear / antagonists & inhibitors*,  metabolism
Taurocholic Acid / analogs & derivatives*,  metabolism,  pharmacology
Reg. No./Substance:
0/Anti-Bacterial Agents; 0/Bile Acids and Salts; 0/Receptors, Cytoplasmic and Nuclear; 0/farnesoid X-activated receptor; 0/fibroblast growth factor 15, mouse; 25696-60-0/tauromuricholic acid; 5E090O0G3Z/Taurocholic Acid; 62031-54-3/Fibroblast Growth Factors; EC 7-alpha-Hydroxylase
Comment In:
Hepatology. 2013 Nov;58(5):1850-3   [PMID:  23775943 ]
Clin Res Hepatol Gastroenterol. 2014 Apr;38(2):129-31   [PMID:  23916556 ]

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