title: Interactions between Gut Microbiota, Host Genetics and Diet Modulate the Predisposition to Obesity and Metabolic Syndrome.
abstract: Obesity, diabetes, and metabolic syndrome result from complex interactions between genetic and environmental factors, including the gut microbiota. To dissect these interactions, we utilized three commonly used inbred strains of mice-obesity/diabetes-prone C57Bl/6J mice, obesity/diabetes-resistant 129S1/SvImJ from Jackson Laboratory, and obesity-prone but diabetes-resistant 129S6/SvEvTac from Taconic-plus three derivative lines generated by breeding these strains in a new, common environment. Analysis of metabolic parameters and gut microbiota in all strains and their environmentally normalized derivatives revealed strong interactions between microbiota, diet, breeding site, and metabolic phenotype. Strain-dependent and strain-independent correlations were found between specific microbiota and phenotypes, some of which could be transferred to germ-free recipient animals by fecal transplantation. Environmental reprogramming of microbiota resulted in 129S6/SvEvTac becoming obesity resistant. Thus, development of obesity/metabolic syndrome is the result of interactions between gut microbiota, host genetics, and diet. In permissive genetic backgrounds, environmental reprograming of microbiota can ameliorate development of metabolic syndrome.
authors: Joslin Diabetes Center and Harvard Medical School, Boston, MA 02215.|Institute for Diabetes and Obesity, Helmholtz Diabetes Center at Helmholtz Center Munich, Munich, 85764, Germany.
authors: Siegfried
authors: S
authors: Ussar
authors: Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63108.|Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St. Louis, MO 63108.
authors: Nicholas W
authors: NW
authors: Griffin
authors: Joslin Diabetes Center and Harvard Medical School, Boston, MA 02215.
authors: Olivier
authors: O
authors: Bezy
authors: Joslin Diabetes Center and Harvard Medical School, Boston, MA 02215.
authors: Shiho
authors: S
authors: Fujisaka
authors: Joslin Diabetes Center and Harvard Medical School, Boston, MA 02215.
authors: Sara
authors: S
authors: Vienberg
authors: Joslin Diabetes Center and Harvard Medical School, Boston, MA 02215.
authors: Samir
authors: S
authors: Softic
authors: Center for Clinical and Translational Metagenomics, Department of Pathology, Brigham & Women's Hospital Harvard Medical School, Boston, MA, 021115.
authors: Luxue
authors: L
authors: Deng
authors: Center for Clinical and Translational Metagenomics, Department of Pathology, Brigham & Women's Hospital Harvard Medical School, Boston, MA, 021115.
authors: Lynn
authors: L
authors: Bry
authors: Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63108.|Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St. Louis, MO 63108.
authors: Jeffrey I
authors: JI
authors: Gordon
authors: Joslin Diabetes Center and Harvard Medical School, Boston, MA 02215.
authors: C Ronald
authors: CR
authors: Kahn
mesh_terms: D000818:Animals; D003920:Diabetes Mellitus / Q000235:genetics* / Q000382:microbiology* / Q000473:pathology; D004032:Diet; D000069196:Gastrointestinal Microbiome; D059647:Gene-Environment Interaction; D005838:Genotype; D007333:Insulin Resistance; D008297:Male; D024821:Metabolic Syndrome / Q000235:genetics* / Q000382:microbiology* / Q000473:pathology; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D009765:Obesity / Q000235:genetics* / Q000382:microbiology* / Q000473:pathology; D010641:Phenotype; D015430:Weight Gain