| Gut Microbiota Regulates Bile Acid Metabolism by Reducing the Levels of Tauro-beta-muricholic Acid, a Naturally Occurring FXR Antagonist. | |
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MedLine Citation:
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PMID: 23395169 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article |
Journal Detail:
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Title: Cell metabolism Volume: 17 ISSN: 1932-7420 ISO Abbreviation: Cell Metab. Publication Date: 2013 Feb |
Date Detail:
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Created Date: 2013-02-11 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101233170 Medline TA: Cell Metab Country: United States |
Other Details:
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Languages: eng Pagination: 225-35 Citation Subset: IM |
Copyright Information:
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Copyright © 2013 Elsevier Inc. All rights reserved. |
Affiliation:
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Wallenberg Laboratory, Department of Molecular and Clinical Medicine and Sahlgrenska Center for Cardiovascular and Metabolic Research, University of Gothenburg, 413 45 Gothenburg, Sweden. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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