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RESEARCH PRODUCT
Modulation of the gut microbiota impacts nonalcoholic fatty liver disease: A potential role for bile acids
Wieneke DijkTom HoubenJ. Mark BrownStanley L. HazenRinke StienstraRinke StienstraJacques VervoortAafke W. F. JanssenGuido J. E. J. HooiveldKo Willems Van DijkLily BoutensLily BoutensSander KerstenFolkert KuipersStéphane MandardZeneng WangNieke Van Der BoltSaeed KatiraeiRonit Shiri-sverdlovsubject
Male0301 basic medicineobesityGut floraGalactansGastroenterologyBiochemistryantibioticsMannansSTEATOHEPATITISVoeding Metabolisme en Genomicachemistry.chemical_compoundLiver diseaseEndocrinologyNon-alcoholic Fatty Liver DiseaseFibrosisAntibioticsPlant GumsNonalcoholic fatty liver diseaseHeptaic inflammationFIBROSIShepatic fibrosisResearch ArticlesHuman Nutrition & HealthbiologyBile acidHumane Voeding & GezondheidMetabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6]Metabolism and GenomicsAnti-Bacterial Agents3. Good healthIntestineL-CARNITINELiverGUAR GUM[ SDV.BBM.GTP ] Life Sciences [q-bio]/Biochemistry Molecular Biology/Genomics [q-bio.GN]Metabolisme en Genomica[SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry Molecular Biology/Genomics [q-bio.GN]Nutrition Metabolism and Genomics[ SDV.MHEP.HEG ] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterologymedicine.medical_specialtymedicine.drug_classBiochemieCelbiologie en ImmunologieQD415-436Gut microbiotaMETABOLISMDiet High-Fatdigestive systemDIET03 medical and health sciencesVoedingINFLAMMATIONINTESTINAL MICROBIOTAInternal medicine[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry Molecular Biology/Genomics [q-bio.GN]medicineAnimalsHepatic inflammationObesityintestineVLAGNutritionInflammationBile acids and saltshepatic inflammationBiological Transport[SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and GastroenterologyCell BiologyGlucose Tolerance Testmedicine.diseaseTaurocholic acidbiology.organism_classification[SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and GastroenterologyGastrointestinal MicrobiomeMice Inbred C57BLMICE030104 developmental biologyEndocrinologychemistryCell Biology and ImmunologySteatohepatitisHepatic fibrosisTRIMETHYLAMINE-N-OXIDEHepatic fibrosisdescription
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.-Janssen, A. W. F., T. Houben, S. Katiraei, W. Dijk, L. Boutens, N. van der Bolt, Z. Wang, J. M. Brown, S. L. Hazen, S. Mandard, R. Shiri-Sverdlov, F. Kuipers, K. Willems van Dijk, J. Vervoort, R. Stienstra, G. J. E. J. Hooiveld, and S. Kersten. Modulation of the gut microbiota impacts nonalcoholic fatty liver disease: a potential role for bile acids.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2017-07-01 |