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

Nature volume 444, pages 1027–1031 (2006)Cite this article

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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References

  1. Xu, J. et al. A genomic view of the human–Bacteroides thetaiotaomicron symbiosis. Science 299, 2074–2076 (2003)

    Article  ADS  CAS  Google Scholar 

  2. Backhed, F., Ley, R. E., Sonnenburg, J. L., Peterson, D. A. & Gordon, J. I. Host–bacterial mutualism in the human intestine. Science 307, 1915–1920 (2005)

    Article  ADS  Google Scholar 

  3. Gill, S. R. et al. Metagenomic analysis of the human distal gut microbiome. Science 312, 1355–1359 (2006)

    Article  ADS  CAS  Google Scholar 

  4. Sonnenburg, J. L. et al. Glycan foraging in vivo by an intestine-adapted bacterial symbiont. Science 307, 1955–1959 (2005)

    Article  ADS  CAS  Google Scholar 

  5. Backhed, F. et al. The gut microbiota as an environmental factor that regulates fat storage. Proc. Natl Acad. Sci. USA 101, 15718–15723 (2004)

    Article  ADS  Google Scholar 

  6. Ley, R. E. et al. Obesity alters gut microbial ecology. Proc. Natl Acad. Sci. USA 102, 11070–11075 (2005)

    Article  ADS  CAS  Google Scholar 

  7. Ley, R. E. et al. Unexpected diversity and complexity of the Guerrero Negro hypersaline microbial mat. Appl. Environ. Microbiol. 72, 3685–3695 (2006)

    Article  CAS  Google Scholar 

  8. Ley, R. E., Peterson, D. A. & Gordon, J. I. Ecological and evolutionary forces shaping microbial diversity in the human intestine. Cell 124, 837–848 (2006)

    Article  CAS  Google Scholar 

  9. Ley, R. E., Turnbaugh, P. J., Klein, S. & Gordon, J. I. Human gut microbes associated with obesity. Nature doi:10.1038/nature4441023a (this issue).

  10. Eckburg, P. B. et al. Diversity of the human intestinal microbial flora. Science 308, 1635–1638 (2005)

    Article  ADS  Google Scholar 

  11. Margulies, M. et al. Genome sequencing in microfabricated high-density picolitre reactors. Nature 437, 376–380 (2005)

    Article  ADS  CAS  Google Scholar 

  12. Kurtz, S. et al. Versatile and open software for comparing large genomes. Genome Biol. 5, R12 (2004)

    Article  Google Scholar 

  13. von Mering, C. et al. STRING: known and predicted protein–protein associations, integrated and transferred across organisms. Nucleic Acids Res. 33, D433–D437 (2005)

    Article  CAS  Google Scholar 

  14. Kanehisa, M., Goto, S., Kawashima, S., Okuno, Y. & Hattori, M. The KEGG resource for deciphering the genome. Nucleic Acids Res. 32, D277–D280 (2004)

    Article  CAS  Google Scholar 

  15. Samuel, B. S. & Gordon, J. I. A humanized gnotobiotic mouse model of host–archaeal–bacterial mutualism. Proc. Natl Acad. Sci. USA 103, 10011–10016 (2006)

    Article  ADS  CAS  Google Scholar 

  16. DeLong, E. F. et al. Community genomics among stratified microbial assemblages in the ocean's interior. Science 311, 496–503 (2006)

    Article  ADS  CAS  Google Scholar 

  17. Rodriguez-Brito, B., Rohwer, F. & Edwards, R. An application of statistics to comparative metagenomics. BMC Bioinformatics 7, 162 (2006)

    Article  Google Scholar 

  18. Duncan, S. H., Hold, G. L., Barcenilla, A., Stewart, C. S. & Flint, H. J. Roseburia intestinalis sp. nov., a novel saccharolytic, butyrate-producing bacterium from human faeces. Int. J. Syst. Evol. Microbiol. 52, 1615–1620 (2002)

    CAS  PubMed  Google Scholar 

  19. Barcenilla, A. et al. Phylogenetic relationships of butyrate-producing bacteria from the human gut. Appl. Environ. Microbiol. 66, 1654–1661 (2000)

    Article  CAS  Google Scholar 

  20. Pryde, S. E., Duncan, S. H., Hold, G. L., Stewart, C. S. & Flint, H. J. The microbiology of butyrate formation in the human colon. FEMS Microbiol. Lett. 217, 133–139 (2002)

    Article  CAS  Google Scholar 

  21. Lozupone, C., Hamady, M. & Knight, R. UniFrac—an online tool for comparing microbial community diversity in a phylogenetic context. BMC Bioinformatics 7, 371 (2006)

    Article  Google Scholar 

  22. Flegal, K. M. & Troiano, R. P. Changes in the distribution of body mass index of adults and children in the US population. Int. J. Obes. Relat. Metab. Disord. 24, 807–818 (2000)

    Article  CAS  Google Scholar 

  23. Webb, P. & Annis, J. F. Adaptation to overeating in lean and overweight men and women. Hum. Nutr. Clin. Nutr. 37, 117–131 (1983)

    CAS  PubMed  Google Scholar 

  24. Rawls, J. F., Mahowald, M. A., Ley, R. E. & Gordon, J. I. Reciprocal gut microbiota transplants from zebrafish and mice to germ-free recipients reveal host habitat selection. Cell 127, 423–433 (2006)

    Article  CAS  Google Scholar 

  25. de Hoon, M. J., Imoto, S., Nolan, J. & Miyano, S. Open source clustering software. Bioinformatics 20, 1453–1454 (2004)

    Article  CAS  Google Scholar 

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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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Authors and Affiliations

  1. Center for Genome Sciences,

    Peter J. Turnbaugh, Ruth E. Ley, Michael A. Mahowald, Elaine R. Mardis & Jeffrey I. Gordon

  2. Genome Sequencing Center, Washington University, Missouri, 63108, St. Louis, USA

    Vincent Magrini & Elaine R. Mardis

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  1. Peter J. Turnbaugh
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  2. Ruth E. Ley
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  4. Vincent Magrini
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  6. Jeffrey I. Gordon
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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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