Microbiome Science

Ruth Ley

5DM31772
  • 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

Our group addresses fundamental questions about the symbiosis between microbiome and human host. We take an evolutionary and genetic approach to identify microbiota with key roles in the host-microbiome relationship, which we then interrogate for their molecular underpinnings in animal and in-vitro models.
We have identified a specific suite of microbes that are responsive to differences in human host genotype. Using a large population of genotyped and phenotyped human twin pairs (>3,000 samples, >1,000 twin pairs with ~60:40 dizygotic/monozygotic), we identified bacteria and archaea whose variation in abundance across the population was partially attributable to host genotype. We then used these heritable microbes as quantitative traits in genome-wide associations to identify human genes linked to the variation in the abundances of heritable microbiota. This approach revealed heritable microbiota, whose relationship with the host we now study in mechanistic detail by building intentional communities in vitro and in vivo. The microbiota-host interactions that we currently focus on include (i) the Christensenellaceae-Methanogen consortium and its relationship to host adiposity; (ii) the Bifidobacteria relationship to host lactase-persistence genotype and lactose intolerance phenotype; and (iii) the impact of Bacteroidetes-derived sphingolipids on host sphingolipid metabolism. In addition to these three main projects outlined below, we continue to explore other exciting areas of host-microbiome interactions.

Future projects are:

Mechanisms of methanogen-bacteria co-aggregation – Work from our group and others has shown that Methanobrevibacter smithii, the most prevalent methanogen in the human gut, co-aggregates with certain bacterial fermenters, allowing for more efficient hydrogen transfer and thus increased growth of both members. The genetic mechanisms that mediate such methanogen-bacteria co-aggregations are not well characterized. Project Leader Nick Youngblut is leading efforts to identify the genetic mechanisms of methanogen-bacteria co-aggregation in the human gut via multiple approaches including comparative genomics, proteomics, and genetics. 

Methanogen mediation of gut microbiome metabolism – The presence or absence of methanogenic archaea in the gut can alter how the microbiome breaks down cellulose, resistant starch, and other recalcitrant substrates to molecules utilized by the host. Understanding how methanogens mediate gut microbiome metabolism has been hindered by the immense complexity of metabolic interactions occurring among all members of the microbiome. Utilizing very simplistic synthetic communities can reduce this complexity, but it can also lose any emergent properties that only arise from highly complex interactions. Project Leader Nick Youngblut is leading efforts to develop methods such as stable isotope probing, untargeted metabolomics, and targeted removal of methanogens from the microbiome in order to investigate how methanogens mediate metabolic interactions in complex communities. 

Bacterial adaptation to mammalian herbivory - In this new and exploratory project, in collaboration with the Weigel group, we will explore how rhizosphere bacteria adapt to the complex lifestyle that bacteria experience when they associate with plants that are eaten and pass through the herbivorous mammalian gut. Using plant and mouse gnotobiotic systems, we will investigate how bacterial species respond to the selection pressures of the mammalian and plant immune systems.

Selected Reading

1) Poole A. C., Goodrich J. K., Youngblut N. D., Luque G. G., Ruaud A., Sutter J. L., Waters J. L., Shi Q., El-Hadidi M., Johnson L. M., Bar H. Y., Huson D. H., Booth J. G. and Ley R. E.: Human salivary amylase gene copy number impacts oral and gut microbiomes. Cell Host & Microbe 25: 553-564. (2019)

2) Moreno-Gallego J. L., Chou S. P., Di Rienzi S. C., Goodrich J. K., Spector T., Bell J. T., Youngblut N., Hewson I., Reyes A. and Ley R. E.: Virome diversity correlates with intestinal microbiome diversity in adult monozygotic twins. Cell Host & Microbe 25: 261-272. (2019)

3) Youngblut N. D., Reischer G. H., Walters W., Schuster N., Walzer C., Stalder G., Ley R. E. and Farnleitner A. H.: Host diet and evolutionary history explain different aspects of gut microbiome diversity among vertebrate clades. Nat Commun 10: 2200. (2019).

4) Goodrich JK, Waters JL, Poole AC, Sutter JL, Koren O, et al. Human genetics shape the gut microbiome. Cell 159: 789-799. (2014)