title: Induction of farnesoid X receptor signaling in germ-free mice colonized with a human microbiota.
abstract: The gut microbiota influences the development and progression of metabolic diseases partly by metabolism of bile acids (BAs) and modified signaling through the farnesoid X receptor (FXR). In this study, we aimed to determine how the human gut microbiota metabolizes murine BAs and affects FXR signaling in colonized mice. We colonized germ-free mice with cecal content from a mouse donor or feces from a human donor and euthanized the mice after short-term (2 weeks) or long-term (15 weeks) colonization. We analyzed the gut microbiota and BA composition and expression of FXR target genes in ileum and liver. We found that cecal microbiota composition differed between mice colonized with mouse and human microbiota and was stable over time. Human and mouse microbiota reduced total BA levels similarly, but the humanized mice produced less secondary BAs. The human microbiota was able to reduce the levels of tauro-β-muricholic acid and induce expression of FXR target genes Fgf15 and Shp in ileum after long-term colonization. We show that a human microbiota can change BA composition and induce FXR signaling in colonized mice, but the levels of secondary BAs produced are lower than in mice colonized with a mouse microbiota.
authors.affiliation: Department of Molecular and Clinical Medicine and Wallenberg Laboratory, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Annika
authors.initials: A
authors.lastname: Wahlström
authors.affiliation: Department of Molecular and Clinical Medicine and Wallenberg Laboratory, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Petia
authors.initials: P
authors.lastname: Kovatcheva-Datchary
authors.affiliation: Department of Molecular and Clinical Medicine and Wallenberg Laboratory, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Marcus
authors.initials: M
authors.lastname: Ståhlman
authors.affiliation: Department of Molecular and Clinical Medicine and Wallenberg Laboratory, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Muhammad-Tanweer
authors.initials: MT
authors.lastname: Khan
authors.affiliation: Department of Molecular and Clinical Medicine and Wallenberg Laboratory, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden Fredrik.Backhed@wlab.gu.se Hanns-Ulrich.Marschall@gu.se.|Novo Nordisk Foundation Center for Basic Metabolic Research, Section for Metabolic Receptology and Enteroendocrinology, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Fredrik
authors.identifier: 0000-0002-4871-8818
authors.initials: F
authors.lastname: Bäckhed
authors.affiliation: Department of Molecular and Clinical Medicine and Wallenberg Laboratory, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden Fredrik.Backhed@wlab.gu.se Hanns-Ulrich.Marschall@gu.se.
authors.forename: Hanns-Ulrich
authors.identifier: 0000-0001-7347-3085
authors.initials: HU
authors.lastname: Marschall
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism; D005243:Feces / Q000382:microbiology; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism*; D000069196:Gastrointestinal Microbiome / Q000235:genetics*; D006801:Humans; D007082:Ileum / Q000378:metabolism / Q000382:microbiology; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000382:microbiology; D008099:Liver / Q000378:metabolism / Q000382:microbiology; D008659:Metabolic Diseases / Q000235:genetics* / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D013656:Taurocholic Acid / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D001647:Bile Acids and Salts; C496283:Fxr1h protein, mouse; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; C108526:fibroblast growth factor 15, mouse; C485506:synapto-pHluorin protein, mouse; C037351:tauromuricholic acid; D013656:Taurocholic Acid; D005346:Fibroblast Growth Factors
keywords: bile acids and salts; biosynthesis and metabolism; enzyme mechanisms and regulation; farnesoid X receptor agonist; farnesoid X receptor antagonist; gut microbiota; humanized mouse models; intestine