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BIOLOGICAL SCIENCES / MICROBIOLOGY
A humanized gnotobiotic mouse model of host–archaeal–bacterial mutualism
Center for Genome Sciences, Washington University School of Medicine, St. Louis, MO 63108
Edited by Kurt J. Isselbacher, Massachusetts General Hospital, Charlestown, MA, and approved May 17, 2006 (received for review March 16, 2006)
Our colons harbor trillions of microbes including a prominent archaeon, Methanobrevibacter smithii. To examine the contributions of Archaea to digestive health, we colonized germ-free mice with Bacteroides thetaiotaomicron, an adaptive bacterial forager of the polysaccharides that we consume, with or without M. smithii or the sulfate-reducing bacterium Desulfovibrio piger. Whole-genome transcriptional profiling of B. thetaiotaomicron, combined with mass spectrometry, revealed that, unlike D. piger, M. smithii directs B. thetaiotaomicron to focus on fermentation of dietary fructans to acetate, whereas B. thetaiotaomicron-derived formate is used by M. smithii for methanogenesis. B. thetaiotaomicron–M. smithii cocolonization produces a significant increase in host adiposity compared with monoassociated, or B. thetaiotaomicron–D. piger biassociated, animals. These findings demonstrate a link between this archaeon, prioritized bacterial utilization of polysaccharides commonly encountered in our modern diets, and host energy balance.
adiposity | energy homeostasis | gut microbial ecology | polysaccharide metabolism | Methanobrevibacter smithii
Author contributions: B.S.S. and J.I.G. designed research; B.S.S. performed research; B.S.S. contributed new reagents/analytic tools; B.S.S. and J.I.G. analyzed data; and B.S.S. and J.I.G. wrote the paper.
Conflict of interest statement: No conflicts declared.
This paper was submitted directly (Track II) to the PNAS office.
Data deposition: The M. smithii gene sequences reported in this paper have been deposited in the GenBank database (accession no. DQ419923).
*To whom correspondence should be addressed at: Washington University School of Medicine, 4444 Forest Park, Campus Box 8510, St. Louis, MO 63108. E-mail: jgordon{at}wustl.edu
© 2006 by The National Academy of Sciences of the USA
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