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

Phones & Faxes: Office Phone:  314-362-7243 Lab Phone:  314-362-3963 Lab 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 and the total number of microbial genes in our aggregate microbial communities is >100-fold greater than the number of genes in our human genome. The vast majority of our symbionts reside in our intestine (as many as 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 microbial and human cells, our genetic landscape as a summation of the genes embedded in our own human genome and in the collective genomes of our body habitat-associated microbial communities (‘microbiome’), 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 gut microbiomes? How much diversity is there within and between human gut microbiomes? How is the human microbiome evolving as a function of our changing diets/lifestyles/cultural traditions, and how does it contribute to our intra- and interpersonal physiologic variations, and predispositions to various diseases? How can we intentionally manipulate the functional properties of our gut microbial communities to optimize their benefit in the context of an individual host, or a population??

To address these important questions, we are culturing and sequencing the genomes of members of the gut microbiota from individuals with various physiologic states so that we can make predictions about what contributions these organisms make to their microbial communities and hosts. We test these predictions in germ-free normal and genetically engineered mice who have been colonized with (i) defined collections of the sequenced wild-type (or mutant) bacteria and archaea (and their viruses), or (ii) unfractionated human gut microbiomes harvested from donors with different physiologic or disease phenotypes (to ascertain how much of the donor’s phenotype can be attributed to their gut microbial communities and what are the molecular mechanisms by which these communities impact host biology).

We employ a variety of experimental and computational methods, including metagenomics (e.g., shotgun sequencing of microbial community DNA to define gene content), functional genomics (RNA-Seq), and mass-spec-based proteomics and metabolomics so that we can compare and contrast the composition and dynamic operations of the gut microbiome in these humanized gnotobiotic mice, which serve as models for common human physiologic processes and disease states. We take the insights we glean from these models and apply them to humans, focusing on mono- and dizygotic twin pairs, their parents and siblings. Since nutritional status is such an important determinant of human health, the major issue we are addressing is the interrelationships between diet and microbial community structure/function, and whether differences in our gut microbial ecology affect our pre-disposition to obesity or malnutrition. These latter studies include characterization of the microbiomes of twins, concordant or discordant for malnutrition, living in several developing countries, who are sampled just prior to, during and after therapeutic food interventions.

Selected Publications:

Muegge, B., Kuczynski, J., Pena, A.G., Fontana, L., Henrissat, B., Knight, R. and Gordon, J.I. Diet drives convergence in gut microbiome functions across mammalian phylogeny and within humans, Science (2011)

Faith, J.J., McNulty, N.P., Rey, F.E., and Gordon, J.I. Predicting a human gut microbiota’s response to diet in gnotobiotic mice Science (2011)

Hansen EE, Lozupone CA, Rey FE, Wu M, Guruge JL, Narra A, Goodfellow J, Zaneveld JR, McDonald DT, Goodrich JA, Heath AC, Knight R, Gordon JI. Pan-genome of the dominant human gut-associated archaeon, Methanobrevibacter smithii, studied in twins.Proc Natl Acad Sci USA. 2011 Mar 15;108 Suppl 1:4599-606. Epub 2011 Feb 2011.

Goodman, A.L., Kallstrom, G., Faith, J.J., Reyes, A., Moore, A., Dantas, G., and Gordon, J.I. Extensive personal human gut microbiota culture collections characterized and manipulated in gnotobiotic mice Proc. Natl. Acad. Sci USA 2011 108: 6252-6257 (2011)

Reyes, A., Haynes, M., Hanson, N., Angly, F., Heath, A., Rohwer, F., and Gordon, J.I. Viruses in the fecal microbiota of monozygotic twins and their mothers.  Nature 466: 334-338 (2010)

Keywords: genomic and metabolic foundations of symbiotic host-microbial relationships in the mammalian gut; human microbiome; metagenomics; microbial ecology and biodiversity; comparative microbial genomics; functional genomics; metabolomics; obesity and malnutrition; studies of monozygotic and dizygotic twins