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| Status |
Public on Jun 06, 2017 |
| Title |
Modulating the gut microbiota by dietary guar gum protects against diet-induced obesity but promotes non-alcoholic steatohepatitis in mice |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Non-alcoholic fatty liver disease (NAFLD) is rapidly becoming 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 and suppressing the gut bacteria via chronic oral administration of antibiotics. Guar gum 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, guar gum 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 guar gum, chronic oral administration of antibiotics effectively suppressed the gut bacteria, decreased portal secondary bile acid levels, and attenuated hepatic inflammation and fibrosis. Neither guar gum or 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.
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| Overall design |
Mice were fed a high-fat, high-cholesterol diet, together with a 20% fructose solution as drinking water, or the same diet in which 10% corn starch (w/w) was replaced by the dietary fiber guar gum. After 18 wks of intervention, livers were removed and used for gene expression profiling.
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| Contributor(s) |
Janssen AW, Houben T, Katiraei S, Boutens L, van der Bolt N, Wang Z, Brown JM, Hazen SL, Shiri-Sverdlov R, Willems van Dijk K, Vervoort J, Stienstra R, Hooiveld GJ, Kersten S |
| Citation(s) |
28533304 |
| Submission date |
Dec 16, 2015 |
| Last update date |
Jun 08, 2017 |
| Contact name |
Guido Hooiveld |
| E-mail(s) |
guido.hooiveld@wur.nl
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| Organization name |
Wageningen University
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| Department |
Div. Human Nutrition & Health
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| Lab |
Nutrition, Metabolism & Genomics Group
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| Street address |
HELIX, Stippeneng 4
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| City |
Wageningen |
| ZIP/Postal code |
NL-6708WE |
| Country |
Netherlands |
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| Platforms (1) |
| GPL11533 |
[MoGene-1_1-st] Affymetrix Mouse Gene 1.1 ST Array [transcript (gene) version] |
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| Samples (16)
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| Relations |
| BioProject |
PRJNA306172 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE76087_RAW.tar |
71.4 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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