title: Interaction between dietary lipids and gut microbiota regulates hepatic cholesterol metabolism.
abstract: The gut microbiota influences many aspects of host metabolism. We have previously shown that the presence of a gut microbiota remodels lipid composition. Here we investigated how interaction between gut microbiota and dietary lipids regulates lipid composition in the liver and plasma, and gene expression in the liver. Germ-free and conventionally raised mice were fed a lard or fish oil diet for 11 weeks. We performed lipidomics analysis of the liver and serum and microarray analysis of the liver. As expected, most of the variation in the lipidomics dataset was induced by the diet, and abundance of most lipid classes differed between mice fed lard and fish oil. However, the gut microbiota also affected lipid composition. The gut microbiota increased hepatic levels of cholesterol and cholesteryl esters in mice fed lard, but not in mice fed fish oil. Serum levels of cholesterol and cholesteryl esters were not affected by the gut microbiota. Genes encoding enzymes involved in cholesterol biosynthesis were downregulated by the gut microbiota in mice fed lard and were expressed at a low level in mice fed fish oil independent of microbial status. In summary, we show that gut microbiota-induced regulation of hepatic cholesterol metabolism is dependent on dietary lipid composition.
authors.affiliation: The Wallenberg Laboratory, Department of Molecular and Clinical Medicine, University of Gothenburg, 41345 Gothenburg, Sweden Robert.Caesar@wlab.gu.se.
authors.forename: Robert
authors.initials: R
authors.lastname: Caesar
authors.affiliation: VTT Technical Research Centre of Finland, FI-02044 VTT, Espoo, Finland.
authors.forename: Heli
authors.initials: H
authors.lastname: Nygren
authors.affiliation: VTT Technical Research Centre of Finland, FI-02044 VTT, Espoo, Finland Steno Diabetes Center A/S, DK-2820 Gentofte, Denmark.
authors.forename: Matej
authors.initials: M
authors.lastname: Orešič
authors.affiliation: The Wallenberg Laboratory, Department of Molecular and Clinical Medicine, University of Gothenburg, 41345 Gothenburg, Sweden Novo Nordisk Foundation Center for Basic Metabolic Research, Section for Metabolic Receptology and Enteroendocrinology, Faculty of Health Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Bäckhed
mesh_terms: D000818:Animals; D002784:Cholesterol / Q000378:metabolism*; D002788:Cholesterol Esters / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects; D004041:Dietary Fats / Q000009:adverse effects / Q000494:pharmacology*; D000069196:Gastrointestinal Microbiome; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D002788:Cholesterol Esters; D004041:Dietary Fats; D002784:Cholesterol
keywords: cholesterol/biosynthesis; fish oil; gene expression; germ-free; lipidomics; liver; microarrays