Mailing and shipping address: Center for Genome Sciences Campus Box 8510 4444 Forest Park Blvd., Room 5401 St. Louis, MO  63108

Phones & Faxes: Office Phone:  314-362-0269 Lab Phone:  314-362-3963 Lab Fax:  314-362-2156 J. Gordon Office Phone: 314-362-7243 J. Gordon Fax: 314-362-7047

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Research Abstract:

Mutually beneficial relationships between microbes and animals are a pervasive feature of life on our microbe-dominated planet. We are no exception: the total number of microbes that colonize our body surfaces exceeds our total number of somatic and germ cells by 10-fold. The majority of our symbionts reside in our intestines (10-100 trillion!), where they provide us with traits we have not had to evolve on our own. In this sense, we should view ourselves as a composite of bacterial, archaeal and human cells, our genetic landscape as a summation of the genes embedded in our own human genome and the genes embedded in the genomes (‘microbiome’) of our microbial partners, and our metabolic features as an amalgamation of human and microbial attributes.

We are interested in the following questions: What are the genomic and metabolic foundations of our mutually beneficial relationships with gut microbes? How do we acquire our microbiota and microbiome? How much diversity is there in our microbiomes: do all humans share an identifiable ‘core’ microbiome? How is the human microbiome evolving as a function of our changing diets, lifestyle, and biosphere? How does it contribute to health and our predispositions to various diseases?  How can we intentionally manipulate our microbial communities to optimize their performance in the context of an individual, or a population?

To address these questions, we are sequencing the genomes of 100 representative members of the human gut microbiota so that we can make predictions about what attributes they possess and what contributions they make to their microbial communities and hosts. We use germ-free normal and genetically engineered mice, colonized with defined collections of sequenced wild-type (or mutant) bacteria and archaea that normally reside in the human gut, to simultaneously monitor host and microbial responses to colonization. We employ a variety of experimental and computational techniques, including metagenomics (sequencing whole microbial community DNA to define its gene content), functional genomics, and mass-spec-based metabolomics, so that we can compare and contrast the composition of the gut microbial community and its microbiome in normal mice and mice that serve as models for common human diseases. We are taking the insights we glean from mouse models and validating them in humans, including mono- and dizygotic twin pairs and their mothers and siblings. One key issue we are addressing is whether differences in our gut microbial ecology affect our pre-disposition to obesity or malnutrition. These latter studies involve humans living in developing countries located in various parts of the world.

Selected Publications:

Samuel, B.S., Hansen, E.E., Manchester, J.K., Coutinho, P.M., Henrissat, B., Fulton, R., Latreille, P.L., Kim, K., Wilson, R.K., and Gordon, J.I. Genomic and metabolic adaptations of Methanobrevibacter smithii to the human gut. Proc. Natl. Acad. Sci. USA 104: 10643-10648 (2007).

Xu, J., Mahowald, M.A., Ley, R.E., Lozupone, C.A., Hamady, M., Martens, E.C., Henrissat, B., Coutinho, P.M., Minx, P., Latreille, P., Cordum, H., Van Brunt, A., Kim, K., Fulton, R.S., Fulton, L.A., Clifton, S.W., Wilson, R.K., Knight, R.D., and Gordon, J.I. Evolution of symbiotic bacteria in the distal human intestine. PLoS Biol. 5: e156 (2007).

Ley, R.E., Turnbaugh, P.J., Klein, S., and Gordon, J.I. Human gut microbes linked to obesity. Nature 444:1022–1023 (2006).

Turnbaugh, P.J., Ley, R.E., Mahowald, M., Magrini, V., Mardis, E.R. and Gordon, J.I. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 444:1027–1031 (2006).

Rawls, J.F., Mahowald, M.A., Ley, R.E., and Gordon, J.I. Reciprocal transplantation of gut microbial communities from zebrafish and mice into germ-free recipients reveals host habitat selection of a microbiota. Cell  127: 423-433 (2006).

Keywords: functional and comparative genomics, genome analysis (microbial), ecology (symbiosis, ecogenomics), computational biology, systems biology, gut development, gut stem cells