TY - JOUR
T1 - High-Fat Diet Determines the Composition of the Murine Gut Microbiome Independently of Obesity
AU - Hildebrandt, Marie A.
AU - Hoffmann, Christian
AU - Sherrill-Mix, Scott A.
AU - Keilbaugh, Sue A.
AU - Hamady, Micah
AU - Chen, Ying Yu
AU - Knight, Rob
AU - Ahima, Rexford S.
AU - Bushman, Frederic
AU - Wu, Gary D.
N1 - Funding Information:
The authors thank the University of Pennsylvania Penn Genomic Frontiers Institute for support and NIH instrument grant S10RR024525 as well as to Elizabeth Costello and Catherine Lozupone for their helpful comments on this manuscript.
Funding Information:
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.).
PY - 2009/11
Y1 - 2009/11
N2 - 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.
AB - 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.
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U2 - 10.1053/j.gastro.2009.08.042
DO - 10.1053/j.gastro.2009.08.042
M3 - Article
C2 - 19706296
AN - SCOPUS:70350110294
SN - 0016-5085
VL - 137
SP - 1716-1724.e2
JO - Gastroenterology
JF - Gastroenterology
IS - 5
ER -