title: Microbiota-induced obesity requires farnesoid X receptor.
abstract: The gut microbiota has been implicated as an environmental factor that modulates obesity, and recent evidence suggests that microbiota-mediated changes in bile acid profiles and signalling through the bile acid nuclear receptor farnesoid X receptor (FXR) contribute to impaired host metabolism. Here we investigated if the gut microbiota modulates obesity and associated phenotypes through FXR.
  
  
  
  We fed germ-free (GF) and conventionally raised (CONV-R) wild-type andFxr-/-mice a high-fat diet (HFD) for 10 weeks. We monitored weight gain and glucose metabolism and analysed the gut microbiota and bile acid composition, beta-cell mass, accumulation of macrophages in adipose tissue, liver steatosis, and expression of target genes in adipose tissue and liver. We also transferred the microbiota of wild-type andFxr-deficient mice to GF wild-type mice.
  
  
  
  The gut microbiota promoted weight gain and hepatic steatosis in an FXR-dependent manner, and the bile acid profiles and composition of faecal microbiota differed betweenFxr-/-and wild-type mice. The obese phenotype in colonised wild-type mice was associated with increased beta-cell mass, increased adipose inflammation, increased steatosis and expression of genes involved in lipid uptake. By transferring the caecal microbiota from HFD-fedFxr-/-and wild-type mice into GF mice, we showed that the obesity phenotype was transferable.
  
  
  
  Our results indicate that the gut microbiota promotes diet-induced obesity and associated phenotypes through FXR, and that FXR may contribute to increased adiposity by altering the microbiota composition.
authors.affiliation: Wallenberg Laboratory, Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Ava
authors.initials: A
authors.lastname: Parséus
authors.affiliation: Wallenberg Laboratory, Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Nina
authors.initials: N
authors.lastname: Sommer
authors.affiliation: Wallenberg Laboratory, Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Felix
authors.initials: F
authors.lastname: Sommer
authors.affiliation: Wallenberg Laboratory, Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Robert
authors.initials: R
authors.lastname: Caesar
authors.affiliation: Wallenberg Laboratory, Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Antonio
authors.initials: A
authors.lastname: Molinaro
authors.affiliation: Wallenberg Laboratory, Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Marcus
authors.initials: M
authors.lastname: Ståhlman
authors.affiliation: Wallenberg Laboratory, Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Thomas U
authors.initials: TU
authors.lastname: Greiner
authors.affiliation: Wallenberg Laboratory, Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Rosie
authors.initials: R
authors.lastname: Perkins
authors.affiliation: Wallenberg Laboratory, Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden.|Section for Metabolic Receptology and Enteroendocrinology, Faculty of Health Sciences, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Bäckhed
mesh_terms: D000273:Adipose Tissue / Q000473:pathology; D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism; D002432:Cecum / Q000382:microbiology; D004041:Dietary Fats / Q000008:administration & dosage; D005234:Fatty Liver / Q000209:etiology* / Q000378:metabolism; D000069467:Fecal Microbiota Transplantation; D005243:Feces / Q000382:microbiology; D000069196:Gastrointestinal Microbiome / Q000235:genetics; D015870:Gene Expression; D005856:Germ-Free Life; D005947:Glucose / Q000378:metabolism; D007249:Inflammation / Q000209:etiology; D050417:Insulin-Secreting Cells / Q000473:pathology; D008264:Macrophages; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000150:complications / Q000378:metabolism* / Q000382:microbiology*; D010641:Phenotype; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics* / Q000378:metabolism*; D015430:Weight Gain; D000099150:Receptor, Farnesoid X-Activated
chemical_list: D001647:Bile Acids and Salts; D004041:Dietary Fats; D005947:Glucose; D018160:Receptors, Cytoplasmic and Nuclear; D000099150:Receptor, Farnesoid X-Activated
keywords: BILE ACID; OBESITY