Modulation of the gut microbiota impacts nonalcoholic fatty liver disease: a potential role for bile acidsNonalcoholic 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. 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. The worldwide epidemic of obesity is the primary driver for the global increase in the prevalence of type 2 diabetes and nonalcoholic fatty liver disease (NAFLD) (1Finucane M.M. Stevens G.A. Cowan M.J. 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G. to in the of chronic liver in PubMed Scopus Google Scholar). the the gut microbiota the development of NAFLD, we the of of the gut microbiota on in a mouse model of NAFLD, we stimulated the gut bacteria by feeding mice the fermentable dietary fiber, guar gum (GG), the fermentable dietary fiber, as as GG digestion in the intestine and is to via and alterations in gut microbiota, feeding GG is an to the role of the gut microbes in in the mouse model of NAFLD, we the on NAFLD of suppressing the gut bacteria a of antibiotics. our data indicate the gut microbiota have a impact on of the gut microbiota by feeding GG of NAFLD, of the gut bacteria oral antibiotics against NAFLD, possibly via changes in the portal of bile acids. studies in and to and In mice a a for energy as from by The The fat of by and with The the with to development of NAFLD The role of in of nonalcoholic fatty liver 2012; PubMed Scopus Google Scholar). 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