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Cell Rep. 2017 Feb 14;18(7):1739-1750. doi: 10.1016/j.celrep.2017.01.062.

Host Genotype and Gut Microbiome Modulate Insulin Secretion and Diet-Induced Metabolic Phenotypes.

Author information

1
Department of Bacteriology, University of Wisconsin-Madison, Madison, WI 53706, USA.
2
Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
3
Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, WI 53706, USA.
4
Department of Statistics, University of Wisconsin-Madison, Madison, WI 53706, USA; Department of Horticulture, University of Wisconsin-Madison, Madison, WI 53706, USA.
5
Department of Pharmacology, Toxicology and Therapeutics, University of Kansas, Kansas City, KS 66160, USA.
6
Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA. Electronic address: adattie@wisc.edu.
7
Department of Bacteriology, University of Wisconsin-Madison, Madison, WI 53706, USA. Electronic address: ferey@wisc.edu.

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.

KEYWORDS:

gut microbiome; insulin secretion; metabolic disease; pancreatic islets

PMID:
28199845
PMCID:
PMC5325228
DOI:
10.1016/j.celrep.2017.01.062
[Indexed for MEDLINE]
Free PMC Article

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