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Gut microbiome science

Ruth Ley

Ruth Ley

  • PhD, University of Colorado, Boulder, 2001
  • Postdoctoral training, University of Colorado, 2001-2004; Post-Doc, Instructor, and Research Assistant Professor, Washington University School of Medicine, 2004-2008
  • Assistant and Associate Professor at Cornell University, 2008-2016
  • Director at the MPI for Developmental Biology since 2016

Research Interest

What is human about the human microbiome? How do the members of the microbial communities that make up the human microbiome differ from those of our close relatives, those of other animals, those that are not host associated? What does it take for a methanogenic archaeon or an anaerobic fermentative bacterium to adapt to life in the human gut? How has human adaptation to new lifestyles and diets, including those that have impacted host genetic variation, shaped the microbiome and its interactions with the host? How do these adaptations relate to health in our modern environments? These are some of the questions that we address in the Department of Microbiome Science.

We work at several scales. We perform large-scale characterization of gut microbiomes with a focus on identifying components that associate with host genetic variation. For example, we characterized the gut microbiomes of over 1,000 pairs of twins from England, and were able to identify heritable microbes. Many have since been validated as heritable in other populations. Heritable microbes are those whose variation in abundance across the population is partially explained by host genotype. In short, this is the list of microbiome species for which people are more or less genetically predisposed.

What is special about heritable microbes? How have heritable microbes adapted to life in the human gut? We use comparative genomics and metagenomics to ascertain the key genetic adaptations to life in the human gut. We use model systems to understand how heritable microbes, such as the Christensenellaceae, methanogens and Bifidobacteria, interact with others to influence host health. We are interested in patterns of adaptation of these microbiota to populations around the world, to better understand the impact on microbiomes of human migration and adaptation to new diets.

Microbiota have co-evolved with their hosts, and host selection for microbiota is based in part on what they can provide the host. In the gut, this includes for instance the products of fermentation, which can enhance host calorie intake from the diet. We are researching the contribution of gut bacteria to lipid metabolism within the host, with an emphasis on sphingolipids.

Finally, we contrast patterns of adaptation and interaction observed in the microbiomes of humans to those of other hosts, such as those of plants. We use these comparisons to shed light on how symbionts of animals are influenced by the time in their life cycle when they are in the environment, between hosts, and to identify aspects of symbionts shared by host-associated microbiota generally.

Selected Reading

1) Di Rienzi S. C., Jacobson J., Kennedy E. A., Bell M. E., Shi Q., Waters J. L., Lawrence P., Brenna J. T., Britton R. A., Walter J., and Ley R. E. (2018) Resilience of small intestinal beneficial bacteria to the toxicity of soybean oil fatty acids. eLife 7:e32581

2) Heaver S. L., Johnson E. L. and Ley R. E. (2018) Sphingolipids in host-microbial interactions. Current Opinion in Microbiology 43: 92-99

3) Goodrich J. K., Davenport E. R., Waters J. L., Clark A. G. and Ley R. E. (2016) Cross-species comparisons of host genetic associations with the microbiome. Science 352, 532-535
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Host genetics and the gut microbiome can both influence metabolic phenotypes. However, whether host genetic variation shapes the gut microbiome and interacts with it to affect host phenotype is unclear. Here, we compared microbiotas across >1,000 fecal samples obtained from the TwinsUK population, including 416 twin pairs. We identified many microbial taxa whose abundances were influenced by host genetics. The most heritable taxon, the family Christensenellaceae, formed a co-occurrence network with other heritable Bacteria and with methanogenic Archaea. Furthermore, Christensenellaceae and its partners were enriched in individuals with low body mass index (BMI). An obese-associated microbiome was amended with Christensenella minuta, a cultured member of the Christensenellaceae, and transplanted to germ-free mice. C. minuta amendment reduced weight gain and altered the microbiome of recipient mice. Our findings indicate that host genetics influence the composition of the human gut microbiome and can do so in ways that impact host metabolism.