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J Lipid Res. 2017 Jul;58(7):1399-1416. doi: 10.1194/jlr.M075713. Epub 2017 May 22.

Modulation of the gut microbiota impacts nonalcoholic fatty liver disease: a potential role for bile acids.

Author information

1
Nutrition, Metabolism, and Genomics Group, Division of Human Nutrition Wageningen University, 6708 WE Wageningen, The Netherlands.
2
Department of Molecular Genetics, Maastricht University, 6200 MD Maastricht, The Netherlands.
3
Departments of Human Genetics Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
4
Department of Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
5
Department of Cellular and Molecular Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, OH 44195.
6
Lipness Team-INSERM Research Center UMR1231 and LabEx LipSTIC, Faculté de Médecine, Université de Bourgogne-Franche Comté, 21079 Dijon CEDEX, France.
7
Departments of Medicine, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
8
Laboratory of Biochemistry, Wageningen University, 6708 WE Wageningen, The Netherlands.
9
Nutrition, Metabolism, and Genomics Group, Division of Human Nutrition Wageningen University, 6708 WE Wageningen, The Netherlands sander.kersten@wur.nl.

Abstract

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide, yet the pathogenesis of NAFLD is only partially understood. Here, we investigated the role of the gut bacteria in NAFLD by stimulating the gut bacteria via feeding mice the fermentable dietary fiber, guar gum (GG), and suppressing the gut bacteria via chronic oral administration of antibiotics. GG feeding profoundly altered the gut microbiota composition, in parallel with reduced diet-induced obesity and improved glucose tolerance. Strikingly, despite reducing adipose tissue mass and inflammation, GG enhanced hepatic inflammation and fibrosis, concurrent with markedly elevated plasma and hepatic bile acid levels. Consistent with a role of elevated bile acids in the liver phenotype, treatment of mice with taurocholic acid stimulated hepatic inflammation and fibrosis. In contrast to GG, chronic oral administration of antibiotics effectively suppressed the gut bacteria, decreased portal secondary bile acid levels, and attenuated hepatic inflammation and fibrosis. Neither GG nor antibiotics influenced plasma lipopolysaccharide levels. In conclusion, our data indicate a causal link between changes in gut microbiota and hepatic inflammation and fibrosis in a mouse model of NAFLD, possibly via alterations in bile acids.

KEYWORDS:

antibiotics; hepatic fibrosis; hepatic inflammation; inflammation; intestine; obesity

PMID:
28533304
PMCID:
PMC5496037
DOI:
10.1194/jlr.M075713
[Indexed for MEDLINE]
Free PMC Article

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