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Gut microbiota regulates bile acid metabolism by reducing the levels of tauro-beta-muricholic acid, a naturally occurring FXR antagonist
Department of Molecular and Clinical Medicine, Sahlgrenska Center for Cardiovascular and Metabolic Research, University of Gothenburg, Gothenburg, Sweden.
Department of Molecular and Clinical Medicine, Sahlgrenska Center for Cardiovascular and Metabolic Research, University of Gothenburg, Gothenburg, Sweden.
Department of Molecular and Clinical Medicine, Sahlgrenska Center for Cardiovascular and Metabolic Research, University of Gothenburg, Gothenburg, Sweden.
VTT Technical Research Centre of Finland, Espoo, Finland.
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2013 (English)In: Cell Metabolism, ISSN 1550-4131, E-ISSN 1932-7420, Vol. 17, no 2, p. 225-235, article id S1550-4131(13)00011-9Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
National Academy of Sciences , 2013. Vol. 17, no 2, p. 225-235, article id S1550-4131(13)00011-9
National Category
Cell Biology Endocrinology and Diabetes
Identifiers
URN: urn:nbn:se:oru:diva-63675DOI: 10.1016/j.cmet.2013.01.003ISI: 000326265000009PubMedID: 23395169Scopus ID: 2-s2.0-84873342775OAI: oai:DiVA.org:oru-63675DiVA, id: diva2:1169240
Funder
Swedish Research CouncilSwedish Diabetes AssociationSwedish Foundation for Strategic Research Swedish Heart Lung FoundationEU, FP7, Seventh Framework Programme, FP7-KBBE-222639Torsten Söderbergs stiftelseRagnar Söderbergs stiftelseÅke Wiberg FoundationMagnus Bergvall FoundationAFA Insurance
Note

Human Frontier of Science Program RGY64/2008

Novo Nordisk

Lars Hierta's

Nanna Svartz

Fredrik foundation

Ingrid Thuring foundation

LUA-ALF grants from Vastra Gotalandsregionen

Stockholm County Council

Available from: 2017-12-22 Created: 2017-12-22 Last updated: 2018-01-30Bibliographically approved

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Hyötyläinen, TuuliaOresic, Matej

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