title: High-fat diet determines the composition of the murine gut microbiome independently of obesity.
abstract: OBJECTIVE
  The composition of the gut microbiome is affected by host phenotype, genotype, immune function, and diet. Here, we used the phenotype of RELMbeta knockout (KO) mice to assess the influence of these factors.
  
  
  METHODS
  Both wild-type and RELMbeta KO mice were lean on a standard chow diet, but, upon switching to a high-fat diet, wild-type mice became obese, whereas RELMbeta KO mice remained comparatively lean. To investigate the influence of diet, genotype, and obesity on microbiome composition, we used deep sequencing to characterize 25,790 16S rDNA sequences from uncultured bacterial communities from both genotypes on both diets.
  
  
  RESULTS
  We found large alterations associated with switching to the high-fat diet, including a decrease in Bacteroidetes and an increase in both Firmicutes and Proteobacteria. This was seen for both genotypes (ie, in the presence and absence of obesity), indicating that the high-fat diet itself, and not the obese state, mainly accounted for the observed changes in the gut microbiota. The RELMbeta genotype also modestly influenced microbiome composition independently of diet. Metagenomic analysis of 537,604 sequence reads documented extensive changes in gene content because of a high-fat diet, including an increase in transporters and 2-component sensor responders as well as a general decrease in metabolic genes. Unexpectedly, we found a substantial amount of murine DNA in our samples that increased in proportion on a high-fat diet.
  
  
  CONCLUSIONS
  These results demonstrate the importance of diet as a determinant of gut microbiome composition and suggest the need to control for dietary variation when evaluating the composition of the human gut microbiome.
authors.affiliation: Division of Gastroenterology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Marie A
authors.initials: MA
authors.lastname: Hildebrandt
authors.forename: Christian
authors.initials: C
authors.lastname: Hoffmann
authors.forename: Scott A
authors.initials: SA
authors.lastname: Sherrill-Mix
authors.forename: Sue A
authors.initials: SA
authors.lastname: Keilbaugh
authors.forename: Micah
authors.initials: M
authors.lastname: Hamady
authors.forename: Ying-Yu
authors.initials: YY
authors.lastname: Chen
authors.forename: Rob
authors.initials: R
authors.lastname: Knight
authors.forename: Rexford S
authors.initials: RS
authors.lastname: Ahima
authors.forename: Frederic
authors.initials: F
authors.lastname: Bushman
authors.forename: Gary D
authors.initials: GD
authors.lastname: Wu
mesh_terms: D000818:Animals; D004032:Diet; D004041:Dietary Fats / Q000008:administration & dosage*; D005260:Female; D006729:Hormones, Ectopic / Q000502:physiology; D036341:Intercellular Signaling Peptides and Proteins; D007422:Intestines / Q000382:microbiology*; D054892:Metagenome; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology*; D012336:RNA, Ribosomal, 16S / Q000235:genetics*
chemical_list: D004041:Dietary Fats; D006729:Hormones, Ectopic; D036341:Intercellular Signaling Peptides and Proteins; D012336:RNA, Ribosomal, 16S; C486522:Retnlb protein, mouse
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