title: Obese Mice Fed a Diet Supplemented with Enzyme-Treated Wheat Bran Display Marked Shifts in the Liver Metabolome Concurrent with Altered Gut Bacteria.
abstract: BACKGROUND
  Enzyme-treated wheat bran (ETWB) contains a fermentable dietary fiber previously shown to decrease liver triglycerides (TGs) and modify the gut microbiome in mice. It is not clear which mechanisms explain how ETWB feeding affects hepatic metabolism, but factors (i.e., xenometabolites) associated with specific microbes may be involved.
  
  
  OBJECTIVE
  The objective of this study was to characterize ETWB-driven shifts in the cecal microbiome and to identify correlates between microbial changes and diet-related differences in liver metabolism in diet-induced obese mice that typically display steatosis.
  
  
  METHODS
  Five-week-old male C57BL/6J mice fed a 45%-lard-based fat diet supplemented with ETWB (20% wt:wt) or rapidly digestible starch (control) (n = 15/group) for 10 wk were characterized by using a multi-omics approach. Multivariate statistical analysis was used to identify variables that were strong discriminators between the ETWB and control groups.
  
  
  RESULTS
  Body weight and liver TGs were decreased by ETWB feeding (by 10% and 25%, respectively; P < 0.001), and an index of liver reactive oxygen species was increased (by 29%; P < 0.01). The cecal microbiome showed an increase in Bacteroidetes (by 42%; P < 0.05) and a decrease in Firmicutes (by 16%; P < 0.05). Metabolites that were strong discriminators between the ETWB and control groups included decreased liver antioxidants (glutathione and α-tocopherol); decreased liver carbohydrate metabolites, including glucose; lower hepatic arachidonic acid; and increased liver and plasma β-hydroxybutyrate. Liver transcriptomics revealed key metabolic pathways affected by ETWB, especially those related to lipid metabolism and some fed- or fasting-regulated genes.
  
  
  CONCLUSIONS
  Together, these changes indicate that dietary fibers such as ETWB regulate hepatic metabolism concurrently with specific gut bacteria community shifts in C57BL/6J mice. It is proposed that these changes may elicit gut-derived signals that reach the liver via enterohepatic circulation, ultimately affecting host liver metabolism in a manner that mimics, in part, the fasting state.
authors: Graduate Group in Nutritional Biology and.|Department of Nutrition.|Obesity and Metabolism Research Unit, USDA-Agricultural Research Service Western Human Nutrition Research Center, Davis, CA.
authors: Dorothy A
authors: DA
authors: Kieffer
authors: Arkansas Children's Nutrition Center and.|Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR.
authors: Brian D
authors: BD
authors: Piccolo
authors: Food Science and Technology Department, and.
authors: Maria L
authors: ML
authors: Marco
authors: Food Science and Technology Department, and.|Department of Animal Life Science, College of Animal Life Sciences, Kangwon National University, Chuncheon, Gangwon-do, Republic of Korea.
authors: Eun Bae
authors: EB
authors: Kim
authors: Department of Microbiology, University of California, Davis, CA.
authors: Michael L
authors: ML
authors: Goodson
authors: Louisiana State University AgCenter, Baton Rouge, LA; and.
authors: Michael J
authors: MJ
authors: Keenan
authors: Graduate Group in Nutritional Biology and.|Department of Nutrition.|Obesity and Metabolism Research Unit, USDA-Agricultural Research Service Western Human Nutrition Research Center, Davis, CA.
authors: Tamara N
authors: TN
authors: Dunn
authors: Department of Animal Science, Aarhus University, Aarhus, Denmark.
authors: Knud Erik Bach
authors: KE
authors: Knudsen
authors: Graduate Group in Nutritional Biology and rmartin@agcenter.lsu.edu shadams@uams.edu.|Department of Nutrition.|Arkansas Children's Nutrition Center and.|Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR.
authors: Sean H
authors: SH
authors: Adams
authors: Graduate Group in Nutritional Biology and rmartin@agcenter.lsu.edu shadams@uams.edu.|Department of Nutrition.|Obesity and Metabolism Research Unit, USDA-Agricultural Research Service Western Human Nutrition Research Center, Davis, CA.
authors: Roy J
authors: RJ
authors: Martin
mesh_terms: D050154:Adiposity; D000821:Animal Feed / Q000032:analysis*; D000818:Animals; D001419:Bacteria / Q000145:classification; D004032:Diet; D004043:Dietary Fiber / Q000032:analysis*; D019587:Dietary Supplements; D041981:Gastrointestinal Tract / Q000382:microbiology*; D005786:Gene Expression Regulation; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000378:metabolism*
keywords: dietary fiber; gut microbiota; metabolomics; transcriptomics; xenobiotic