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.
This is a preview of subscription content
Subscribe to Journal
Get full journal access for 1 year
only $3.90 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Tax calculation will be finalised during checkout.
Get time limited or full article access on ReadCube.
All prices are NET prices.
Xu, J. et al. A genomic view of the human–Bacteroides thetaiotaomicron symbiosis. Science 299, 2074–2076 (2003)
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)
Gill, S. R. et al. Metagenomic analysis of the human distal gut microbiome. Science 312, 1355–1359 (2006)
Sonnenburg, J. L. et al. Glycan foraging in vivo by an intestine-adapted bacterial symbiont. Science 307, 1955–1959 (2005)
Backhed, F. et al. The gut microbiota as an environmental factor that regulates fat storage. Proc. Natl Acad. Sci. USA 101, 15718–15723 (2004)
Ley, R. E. et al. Obesity alters gut microbial ecology. Proc. Natl Acad. Sci. USA 102, 11070–11075 (2005)
Ley, R. E. et al. Unexpected diversity and complexity of the Guerrero Negro hypersaline microbial mat. Appl. Environ. Microbiol. 72, 3685–3695 (2006)
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)
Ley, R. E., Turnbaugh, P. J., Klein, S. & Gordon, J. I. Human gut microbes associated with obesity. Nature doi:10.1038/nature4441023a (this issue).
Eckburg, P. B. et al. Diversity of the human intestinal microbial flora. Science 308, 1635–1638 (2005)
Margulies, M. et al. Genome sequencing in microfabricated high-density picolitre reactors. Nature 437, 376–380 (2005)
Kurtz, S. et al. Versatile and open software for comparing large genomes. Genome Biol. 5, R12 (2004)
von Mering, C. et al. STRING: known and predicted protein–protein associations, integrated and transferred across organisms. Nucleic Acids Res. 33, D433–D437 (2005)
Kanehisa, M., Goto, S., Kawashima, S., Okuno, Y. & Hattori, M. The KEGG resource for deciphering the genome. Nucleic Acids Res. 32, D277–D280 (2004)
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)
DeLong, E. F. et al. Community genomics among stratified microbial assemblages in the ocean's interior. Science 311, 496–503 (2006)
Rodriguez-Brito, B., Rohwer, F. & Edwards, R. An application of statistics to comparative metagenomics. BMC Bioinformatics 7, 162 (2006)
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)
Barcenilla, A. et al. Phylogenetic relationships of butyrate-producing bacteria from the human gut. Appl. Environ. Microbiol. 66, 1654–1661 (2000)
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)
Lozupone, C., Hamady, M. & Knight, R. UniFrac—an online tool for comparing microbial community diversity in a phylogenetic context. BMC Bioinformatics 7, 371 (2006)
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)
Webb, P. & Annis, J. F. Adaptation to overeating in lean and overweight men and women. Hum. Nutr. Clin. Nutr. 37, 117–131 (1983)
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)
de Hoon, M. J., Imoto, S., Nolan, J. & Miyano, S. Open source clustering software. Bioinformatics 20, 1453–1454 (2004)
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.
The authors declare no competing financial interests.
About this article
Cite this article
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
Pharmacologically induced weight loss is associated with distinct gut microbiome changes in obese rats
BMC Microbiology (2022)
Weight-loss in obese dogs promotes important shifts in fecal microbiota profile to the extent of resembling microbiota of lean dogs
Animal Microbiome (2022)
Effects of rumen-protected creatine pyruvate on blood biochemical parameters and rumen fluid characteristics in transported beef cattle
BMC Veterinary Research (2022)
Journal of Experimental & Clinical Cancer Research (2022)
Effects of personalized diets by prediction of glycemic responses on glycemic control and metabolic health in newly diagnosed T2DM: a randomized dietary intervention pilot trial
BMC Medicine (2022)