Welcome to the Ley Lab Home Page. We are now the Department of Microbiome Science, Max Planck Institute for Developmental Biology, Tübingen, Germany. For opportunities to join the lab, please visit the Join Us page.
Research Focus: We are interested in the co-evolution of humans with their microbiomes.
The microbiome is environmentally acquired when people are born and rapidly builds up on the body’s surfaces to constitute a critically important layer of cells. The majority of microbial cells inhabit the gastrointestinal tract, where they provide fundamental services to the host, from digestion of dietary fiber to pathogen exclusion. The composition of microbiomes varies between individuals in composition and function. Functional differences can in turn impact health. The microbiome is increasingly viewed as a target for therapeutic interventions for diseases ranging from malnutrition to chronic inflammation.
What is the evolutionary history of the microbiome? How does that history impact our present-day interactions with our microbial cells? The last ten years has seen an enormous influx of information about the composition of the gut microbiome across populations, but most of the effort to describe microbiomes has centered on the Western world. Our goal is to acquire a comprehensive view of the biogeographical patterns of microbial diversity across human populations. This will allow us to understand better how commensal microbes have migrated with their human hosts across the globe and how modernization impacts diversity.
How do microbe-microbe interactions shape community composition and impact the host? Our genetic studies in twins led to the discovery that the family Christensenellaceae co-occurs with other microbes such as methanogens and is enriched in lean versus obese individuals. Furthermore, the lean host phenotype can be recapitulated in gnotobiotic mice inoculated with these taxa. We are investigating the basis for the co-occurrence patterns and the mechanisms underlying the phenotypic effects these bacteria induce in their hosts. Since little is known about these anaerobic microbiota, we employ in-vitro and in-vivo molecular studies, as well as the tools of genomics and metagenomics, to learn more about important commensals.
Host-microbial interactions at the molecular level: The gut microbiota are engaged in molecular exchanges with their hosts. We are particularly interested in how bacterial flagellins interact with the host receptor, TLR5, for instance, and in how bacterial sphingolipids produced in the gut impact host metabolism. These, and other lines of inquiry in the lab, query at the molecular level how host and microbe co-evolve to maximize fitness.
Goodrich, J. K. , E. R. Davenport, M. A. Jackson, M. Beaumont, R. Knight, T. D. Spector, J. T. Bell, A. G. Clark, R. E. Ley. Genetic determinants of the gut microbiome assessed in UK Twins. Cell Host & Microbe 19:731-43. (2016)
Goodrich*, J. K., E. R. Davenport*, J. L. Waters*, A. G. Clark and R. E. Ley. Cross-species comparisons of host genetic associations with the microbiome. Science 352: 532-535. (2016)
Goodrich, J. K., J. L. Waters, A. C. Poole, J. L. Sutter, O. Koren, R. Blekhman, M. Beaumont, W. Van Treuren, R. Knight, J. T. Bell, T. D. Spector, A. G. Clark and R. E. Ley. Human genetics shape the gut microbiome. Cell 159: 789-799. (2014)
Cullender, T. C., B. Chassaing, A. Janzon, K. Kumar, C. Muller, J. J. Werner, L. T. Angenent, M. E. Bell, A. G. Hay, D. A. Peterson, J. Walter, M. Vijay-Kumar, A. T. Gewirtz and R. E. Ley. Innate and adaptive immunity interact to quench microbiome flagellar motility in the gut. Cell Host Microbe 14: 571-581. (2013)
DiRienzi*, S. C., I. Sharon*, K. C. Wrighton, O. Koren, L. A. Hug, B. C. Thomas, J. K. Goodrich, J. T. Bell, T. D. Spector, J. F. Banfielda and R. E. Ley. The human gut and groundwater harbor non-photosynthetic bacteria belonging to a new candidate phylum sibling to Cyanobacteria. eLife 2:e01102 (2013)
Koren, O., J. K. Goodrich, T. C. Cullender, A. Spor, K. Laitinen, H. Backhed, A. Gonzalez, J. J. Werner, L. T. Angenent, R. Knight, F. Backhed, E. Isolauri, S. Salminen and R. E. Ley. Remodeling of the gut microbiome and metabolic changes during pregnancy. Cell 150: 1-11 (2012).