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 vast 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 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 microbial community (microbiota) and its microbiome? How much diversity is there in our gut microbiota and microbiomes: do all humans share an identifiable ‘core’ (gut) microbiome? How is the human gut microbiome evolving as a function of our changing diets, lifestyle, and biosphere and how does it contribute to our health 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 questions, we are sequencing the genomes of 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 methods and computational techniques, including metagenomics (e.g., shotgun sequencing of microbial community DNA to define its gene content), functional genomics (profiling mRNAs expressed by the microbiome), and mass-spec-based metabolomics, so that we can compare and contrast the composition and dynamic operations of the gut microbiota and its microbiome in these humanized gnotobiotic mice, that serve as models for common human physiologic processes and disease states. We are taking the methods and insights we glean from our mouse models and applying them to humans, focusing on mono- and dizygotic twin pairs and their mothers and siblings. Since nutritional status is such an important determinant of human health, a major issue we are addressing is the interrelationships between diet and gut microbial community structure/function, and whether differences in our gut microbial ecology affect our pre-disposition to obesity or malnutrition. These latter studies involve characterization of the gut microbiota/microbiome of twins, concordant or discordant for malnutrition, living in several developing countries, who are sampled just prior to, during and after treatment.
Selected Publications:
Turnbaugh, PJ, Ley RE, Mahowald M, Magrini V, Mardis ER and Gordon JI. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 2006 444: 1027–1031.
Turnbaugh PJ, Ley RE, Hamady M, Fraser-Liggett C, Knight R. and Gordon JI. The human microbiome project. Nature 2007 449:804-810 .
Ley RE, Hamady M, Lozupone C, Turnbaugh P, Ramey RR, Bircher S, Schlegel ML, Tucker TA, Schrenzel MD, Knight RD, and Gordon JI. Evolution of mammals and their gut microbes. Science 2008 320:1647-1651.
Mahowald, MA, Rey, FE, Seedorf, H, Turnbaugh, PJ, Fulton, RS, Wollam, A, Shah, N, Wang, C, Magrini, V, Wilson, RK, Cantarel, BL Coutinho, PM, Henrissat, B, Crock, LW, Russell, A, Verberkmoes, NC, Hettich, RL, and Gordon, JI. Characterizing a model human gut microbiota composed of members of its two dominant bacterial phyla. Proc. Natl. Acad. Sci. USA 2009 106:5859-5864.
Turnbaugh PJ, Hamady M, Yatsunenko T, Cantarel BL, Duncan A, Ley RE, Sogin ML, Jones WJ, Roe BA, Affourtit JP, Egholm M, Henrissat B, Heath AC, Knight R and Gordon JI. A core gut microbiome in obese and lean twins. Nature 2009 457:480-484.
Last Updated: 08/19/2009 |