An obesity-associated gut microbiome with increased capacity for energy harvest

Abstract

The worldwide obesity epidemic is stimulating efforts to identify host and environmental factors that affect energy balance. Comparisons of the distal gut microbiota of genetically obese mice and their lean littermates, as well as those of obese and lean human volunteers have revealed that obesity is associated with changes in the relative abundance of the two dominant bacterial divisions, the Bacteroidetes and the Firmicutes. Here we demonstrate through metagenomic and biochemical analyses that these changes affect the metabolic potential of the mouse gut microbiota. Our results indicate that the obese microbiome has an increased capacity to harvest energy from the diet. Furthermore, this trait is transmissible: colonization of germ-free mice with an ‘obese microbiota’ results in a significantly greater increase in total body fat than colonization with a ‘lean microbiota’. These results identify the gut microbiota as an additional contributing factor to the pathophysiology of obesity.

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Figure 1: Comparison of data sets obtained from the caecal microbiomes of obese and lean littermates.
Figure 2: Microbiomes cluster according to host genotype.
Figure 3: Biochemical analysis and microbiota transplantation experiments confirm that the ob/ob microbiome has an increased capacity for dietary energy harvest.

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Acknowledgements

We thank our colleagues B. Samuel, F. Backhed, D. O’Donnell, M. Karlsson, M. Hickenbotham, K. Haub, L. Fulton, J. Crowley, T. Coleman, C. Semenkovich, V. Markowitz and E. Szeto for their assistance. This work was supported by grants from the NIH and the W.M. Keck Foundation.

This Whole Genome Shotgun project has been deposited at DDBJ/EMBL/GenBank under the project accession AATA00000000–AATF00000000. The version described in this paper is the first version, AATA01000000–AATF01000000. All 454 GS20 reads have been deposited in the NCBI Trace Archive. PCR-derived 16S rRNA gene sequences are deposited in GenBank under the accession numbers EF95962-100118. Annotated sequences are also available for further analysis in IMG/M (http://img.jgi.doe.gov/m). Reprints and permissions information is available at www.nature.com/reprints. The authors declare no competing financial interests.

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Correspondence to Jeffrey I. Gordon.

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This file contains Supplementary Discussion, Supplementary Methods, Supplementary Notes, Supplementary Figures S1-S6 and Supplementary Tables S1-S9.

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Turnbaugh, P., Ley, R., Mahowald, M. et al. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 444, 1027–1031 (2006). https://doi.org/10.1038/nature05414

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