Genomic and metabolic adaptations of Methanobrevibacter smithii to the human gut

Buck S. Samuel, Elizabeth E. Hansen, Jill K. Manchester, Pedro M. Coutinho, Bernard Henrissat, Robert Fulton, Philippe Latreille, Kung Kim, Richard K. Wilson, Jeffrey I. Gordon

Research output: Contribution to journalArticlepeer-review

334 Scopus citations

Abstract

The human gut is home to trillions of microbes, thousands of bacterial phylotypes, as well as hydrogen-consuming methanogenic archaea. Studies in gnotobiotic mice indicate that Methanobrevibacter smithii, the dominant archaeon in the human gut ecosystem, affects the specificity and efficiency of bacterial digestion of dietary polysaccharides, thereby influencing host calorie harvest and adiposity. Metagenomic studies of the gut microbial communities of genetically obese mice and their lean littermates have shown that the former contain an enhanced representation of genes involved in polysaccharide degradation, possess more archaea, and exhibit a greater capacity to promote adiposity when transplanted into germ-free recipients. These findings have led to the hypothesis that M. smithii may be a therapeutic target for reducing energy harvest in obese humans. To explore this possibility, we have sequenced its 1,853,160-bp genome and compared it to other human gut-associated M. smithii strains and other Archaea. We have also examined M. smithii's transcriptome and metabolome in gnotobiotic mice that do or do not harbor Bacteroides thetaiotaomicron, a prominent saccharolytic bacterial member of our gut microbiota. Our results indicate that M. smithii is well equipped to persist in the distal intestine through (i) production of surface glycans resembling those found in the gut mucosa, (ii) regulated expression of adhesin-like proteins, (iii) consumption of a variety of fermentation products produced by saccharolytic bacteria, and (iv) effective competition for nitrogenous nutrient pools. These findings provide a framework for designing strategies to change the representation and/or properties of M. smithii in the human gut microbiota.

Original languageEnglish
Pages (from-to)10643-10648
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number25
DOIs
StatePublished - Jun 19 2007

Keywords

  • Archaeal-bacterial mutualism
  • Comparative microbial genomics
  • Functional genomics and metabolomics
  • Gnotobiotic mice
  • Human gut microbiota

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