High-Fat Diet Determines the Composition of the Murine Gut Microbiome Independently of Obesity
Received 27 March 2009; accepted 6 August 2009. published online 25 August 2009.
Background & Aims
The composition of the gut microbiome is affected by host phenotype, genotype, immune function, and diet. Here, we used the phenotype of RELMβ knockout (KO) mice to assess the influence of these factors.
Methods
Both wild-type and RELMβ KO mice were lean on a standard chow diet, but, upon switching to a high-fat diet, wild-type mice became obese, whereas RELMβ 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 RELMβ 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.
⁎Division of Gastroenterology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
‡Division of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
§Department of Computer Science, University of Colorado, Boulder, Colorado
∥Department of Chemistry and Biochemistry, University of Colorado, Boulder, Colorado
¶Division of Endocrinology, Diabetes, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
Reprint requests Address requests for reprints to: Gary D. Wu, MD, Division of Gastroenterology, University of Pennsylvania School of Medicine, Suite 600, Clinical Research Building, 415 Curie Blvd, Philadelphia, Pennsylvania 19104. fax: (215) 573-2024; or Frederic D. Bushman, PhD, Department of Microbiology, University of Pennsylvania School of Medicine, 425 Johnson Pavilion, 3610 Hamilton Walk, Philadelphia, Pennsylvania 19104-6076. fax: (215) 573-4856
F.B. and G.D.W. contributed equally to this study.
Conflicts of interest The authors disclose no conflicts.
Funding Supported by NIH grants AI39368 (to G.D.W.), DK062348 (to R.S.A.), and DK078669 and HG004872 (to R.K.); the Molecular Biology and Mouse Physiology Cores of NIH/NIDDK center grants DK50306 and DK019525, respectively; and in part by the Penn Genome Frontiers Institute, NIH instrument grant S10RR024525, and a grant with the Pennsylvania Department of Health (to F.D.B. and G.D.W.).
ABSTRACT
High-Fat Diet Determines the Composition of the Murine Gut Microbiome Independently of Obesity