title: Host Genotype and Gut Microbiome Modulate Insulin Secretion and Diet-Induced Metabolic Phenotypes.
abstract: Genetic variation drives phenotypic diversity and influences the predisposition to metabolic disease. Here, we characterize the metabolic phenotypes of eight genetically distinct inbred mouse strains in response to a high-fat/high-sucrose diet. We found significant variation in diabetes-related phenotypes and gut microbiota composition among the different mouse strains in response to the dietary challenge and identified taxa associated with these traits. Follow-up microbiota transplant experiments showed that altering the composition of the gut microbiota modifies strain-specific susceptibility to diet-induced metabolic disease. Animals harboring microbial communities with enhanced capacity for processing dietary sugars and for generating hydrophobic bile acids showed increased susceptibility to metabolic disease. Notably, differences in glucose-stimulated insulin secretion between different mouse strains were partially recapitulated via gut microbiota transfer. Our results suggest that the gut microbiome contributes to the genetic and phenotypic diversity observed among mouse strains and provide a link between the gut microbiome and insulin secretion.
authors.affiliation: Department of Bacteriology, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Julia H
authors.initials: JH
authors.lastname: Kreznar
authors.affiliation: Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Mark P
authors.initials: MP
authors.lastname: Keller
authors.affiliation: Department of Bacteriology, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Lindsay L
authors.initials: LL
authors.lastname: Traeger
authors.affiliation: Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Mary E
authors.initials: ME
authors.lastname: Rabaglia
authors.affiliation: Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Kathryn L
authors.initials: KL
authors.lastname: Schueler
authors.affiliation: Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Donald S
authors.initials: DS
authors.lastname: Stapleton
authors.affiliation: Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Wen
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Department of Bacteriology, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Eugenio I
authors.initials: EI
authors.lastname: Vivas
authors.affiliation: Department of Statistics, University of Wisconsin-Madison, Madison, WI 53706, USA; Department of Horticulture, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Brian S
authors.initials: BS
authors.lastname: Yandell
authors.affiliation: Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Aimee Teo
authors.initials: AT
authors.lastname: Broman
authors.affiliation: Department of Pharmacology, Toxicology and Therapeutics, University of Kansas, Kansas City, KS 66160, USA.
authors.forename: Bruno
authors.initials: B
authors.lastname: Hagenbuch
authors.affiliation: Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA. Electronic address: adattie@wisc.edu.
authors.forename: Alan D
authors.initials: AD
authors.lastname: Attie
authors.affiliation: Department of Bacteriology, University of Wisconsin-Madison, Madison, WI 53706, USA. Electronic address: ferey@wisc.edu.
authors.forename: Federico E
authors.initials: FE
authors.lastname: Rey
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism; D003920:Diabetes Mellitus / Q000235:genetics* / Q000382:microbiology*; D059305:Diet, High-Fat / Q000009:adverse effects; D000069196:Gastrointestinal Microbiome / Q000502:physiology*; D041981:Gastrointestinal Tract / Q000382:microbiology*; D014644:Genetic Variation / Q000235:genetics; D005838:Genotype; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology; D008297:Male; D051379:Mice; D064307:Microbiota / Q000502:physiology*; D010641:Phenotype
chemical_list: D001647:Bile Acids and Salts; D007328:Insulin
keywords: gut microbiome; insulin secretion; metabolic disease; pancreatic islets