High Fat Diet Determines the Composition of the Murine Gut Microbiome Independently of Obesity

By Marie A. Hildebrandt, C. Hoffman, S. Sherrill-Mix, S. Keilbaugh, Micah Hamady, Ying-Yu Chen, Rob Knight, R. Ahima, Frederic D. Bushman, Gary D. Wu. Gastroenterology, 2009

1,521 citations recorded by the source corpus.

Background 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 and Results 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 while 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. 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 (i.e. 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 due to a high fat diet, including an increase in transporters and two-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.

Subfields: Food Science, Infectious Diseases, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/645e921d1ecba72d438754b82fd5f5373a4bbd0f

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Food Science

1. Patrice D Cani
2. W. D. de Vos
3. M. Derrien
4. H. Smidt
5. R. Gambino
6. G. Musso
7. Rob Knight
8. P. Navarrete

In Infectious Diseases

1. Rob Knight
2. M. Johansson
3. G. Hansson
4. N. Delzenne
5. J. Rawls
6. F. Bäckhed
7. Patrice D Cani
8. A. Neyrinck

In Molecular Biology

1. Patrice D Cani
2. Rob Knight
3. W. D. de Vos
4. F. Bäckhed
5. N. Delzenne
6. Dan Knights
7. Jesse Stombaugh
8. J. Rawls

Citations in the corpus

• Diet-Induced Dysbiosis of the Intestinal Microbiota and the Effects on Immunity and Disease (2012, background): “δ-Proteobacteria Increased [61] Animal milk fat δ-Proteobacteria Increased [62]”
• Impacts of Gut Bacteria on Human Health and Diseases (2015, background): “In that study, fermentation of polyphenols increased proliferation of Bifidobacteria and decreased the ratio of Firmicutes to Bacteroidetes, compared to controls.”
• Environmental and Gut Bacteroidetes: The Food Connection (2011, background): “An independent study on a murine model showed that a high-fat diet was associated with a decrease in more than 30 lineages within the Bacteroidetes phylum, including in the Bacteroidaceae, Prevotellaceae, and Rikenellaceae families (Hildebrandt et al., 2009).”
• Impact of Omega-3 Fatty Acids on the Gut Microbiota (2017, methodology): “(2009) [38] C57BL/6 and β resistin-like molecule β knockout mice High-fat diet (45% fat) for 21 weeks High fat diet caused changed in microbiota composition with a decrease in Bacteroidetes phylum and an increase in both Firmicutes and Proteobacteria phyla.”
• The Impact of Diet and Lifestyle on Gut Microbiota and Human Health (2014, background): “A study using a murine (RELMβ) knockout model showed that dietary fat-induced changes to gut microbiome composition were independent of obesity [127].”
• Bifidobacteria or fiber protect against diet-induced microbiota-mediated colonic mucus deterioration (2017, result): “Similar to previous studies (Hildebrandt et al., 2009; Turnbaugh et al., 2008, 2009), we observed increased abundance of taxa belonging to Firmicutes and reduced abundance of Bacteroidetes and Actinobacteria in the colonic lumen of mice fed a WSD (Figure 3A and Table S1).”
• Interactions between gut microbiota and host metabolism predisposing to obesity and diabetes. (2011, methodology): “When RELMβ KO and RELMβ wild-type mice were switched from a standard diet to a high-fat diet, both groups underwent similar changes in gut microbiota composition, indicating that effects of diet dominated over the obese phenotype (17).”
• Stress & the gut-brain axis: Regulation by the microbiome (2017, neutral): “…past few years, including evidence that high-fat diet feeding promotes a “ leaky gut ” (i.e., increased intestinal permeability (Cani et al., 2008; Hildebrandt et al., 2009; Kim et al., 2012)), similar to the effect of chronic stress alone (Gareau et al., 2008; Maes and Leunis, 2008;…”
• A polyphenol-rich cranberry extract protects from diet-induced obesity, insulin resistance and intestinal inflammation in association with increased Akkermansia spp. population in the gut microbiota of mice (2014, methodology): “All procedures were previously approved by the Laval University Animal Ethics Committee.”
• The Microbiome and Butyrate Regulate Energy Metabolism and Autophagy in the Mammalian Colon (2011, neutral): “These microbiota and their genomes, referred to collectively as the microbiome, are being characterized by metagenomic sequencing as part of the Human Microbiome Project (Gill et al., 2006; Hildebrandt et al., 2009; Kurokawa et al., 2007; Qin et al.; Turnbaugh et al., 2009; Turnbaugh et al., 2007).”