Research

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 publications, by topic:

 

The following publications address the link between human genotype and microbiome:

Goodrich J. K., Davenport E. R., Clark A. G., Ley R. E.: The relationship between the human genome and microbiome comes into view. Annu Rev Genet (2017). 

Goodrich J. K., Davenport E. R., Waters J. L., Clark A. G. and Ley R. E.: Cross-species comparisons of host genetic associations with the microbiome. Science 352: 532-535. (2016)

Goodrich J. K., Davenport E. R., Jackson M. A., Beaumont M., Knight R., Spector T. D., Bell J. T., Clark A. G. and Ley R. E.: Genetic determinants of the gut microbiome assessed in UK Twins. Cell Host Microbe 19: 731-43. (2016).

Davenport E. R., Goodrich J. K., Bell J. T., Spector T. D., Ley R. E. and Clark A. G.: ABO antigen and secretor statuses are not associated with gut microbiota composition in 1,500 twins. BMC Genomics 17: 941. (2016).

Beaumont M., Goodrich J. K., Jackson M. A., Yet I., Davenport E. R., Vieira-Silva S., Debelius J., Pallister T., Mangino M., Raes J., Knight R., Clark A. G., Ley R. E., Spector T. D. and Bell J. T.: Heritbale components of the human fecal microbiome are associated with visceral fat. Genome Biol. 17: 189. (2016).

Goodrich J. K., Waters J. L., Poole A. C., Sutter J. L., Koren O., Blekhman R., Beaumont M., Van Treuren W., Knight R., Bell J. T., Spector T. D., Clark A. G. and Ley R. E.: Human genetics shape the gut microbiome. Cell 159: 789-799. (2014).

Blekhman R., Goodrich J. K., Huang K., Sun Q., Bukowski R., Bell J. T., Spector T. D., Keinan A., Ley R. E., Gevers D. and Clark A. G.: Host genetic variation impacts microbiome composition across body sites. Genome Biol. 16: 191. (2015).

Peiffer J., Spor A., Jin Z., Koren O., Tringe S. G., Dangl J. L., Buckler E. S. and Ley R. E.: Diversity and heritability of the Maize rhizosphere microbiome under field conditions. Proc Natl Acad Sci USA 110: 6548-6553. (2013). 

Spor A., Koren O. and Ley R. E.:  Unraveling the effects of environment and host genotype on the gut microbiome.  Nature Reviews Microbiology 9:279-90. (2011).

 

Selected publications that relate to host selection of microbial traits:

Cullender T. C., Chassaing B., Janzon A., Kumar K., Muller C., Werner J. J., Angenent L. T., Bell M. E., Hay A. G., Peterson D. A., Walter J., Vijay-Kumar M., Gewirtz A. T. and Ley R. E.: Innate and adaptive immunity interact to quench microbiome flagellar motility in the gut. Cell Host Microbe 14: 571-581. (2013).

Di Rienzi S. C., Sharon I., Wrighton K. C., Koren O., Hug L. A., Thomas B. C., Goodrich J. K., Bell J. T., Spector T. D., Banfield J. F. and Ley R. E.:  The human gut and groundwater harbor non-photosynthetic bacteria belonging to a new candidate phylum sibling to Cyanobacteria. eLife 2:e01102. (2013).

Koren O., Goodrich J. K., Cullender T. C., Spor A., Laitinen K., Backhed H., Gonzalez A., Werner J. J., Angenent L. T., Knight R., Backhed F. , Isolauri E., Salminen S. and Ley R. E.: Remodeling of the gut microbiome and metabolic changes during pregnancy. Cell 150: 1-11. (2012). 

Vaishnava S., Yamamoto M., Severson K. M., Ruhn K. A., Yu X., Koren O., Ley R. E., Wakeland E. K. and Hooper L. V.:  The antibacterial lectin RegIIIγ promotes the spatial segregation of microbiota and host in the intestine. Science 334: 255-258. (2011).

Koenig J. E., Spor A., Scalfone N., Fricker A. D., Stombaugh J., Knight R., Angenent L. T. and Ley R. E.: 2011. Succession of microbial consortia in the developing infant gut microbiome. Proceedings of the National Academy of Sciences USA 108 Suppl1: 4578-4585. (2011).

Walter J and Ley R. E.: The human gut microbiome: ecology and recent evolutionary changes. Annual Reviews of Microbiology 65: 411-429. (2011).

 

Selected publications that contribute to methods in the field:

Goodrich J. K., Di Renzi S. C., Poole A. C., Koren O., Walters W. A., Caporaso G., Knight R. and Ley R. E.: Conducting a Microbiome Study. Cell 17: 250-262. (2014).

Koren O., Knights D., Gonzalez A., Waldron L., Segata N., Knight R., Huttenhower C., Ley R. E.: A guide to Enterotypes across the human body: A meta-analysis of microbial community structures in human microbiome datasets. PLoS Comput Biol 9: e1002863. (2013).

Werner J. J., Koren O., Hugenholtz P., DeSantis T. Z., Walters W. A., Caporaso J. G., Angenent L. T., Knight R. and Ley R. E.:  Impact of training sets on classification of high-throughput bacterial 16S rRNA Gene Surveys. The ISME Journal 6: 94-103. (2012). 

Yilmaz P., the MIMARKS consortium*.  The “Minimal Information about a MARKer gene Sequence” (MIMARKS) specification.  Nature Biotechnology 29: 415-420. (2011). 

Knights D., Kuczynski J. , Koren O., Ley R. E., Field D., Knight R., DeSantis T. Z. and Kelley S. T.: Supervised classification of microbiota mitigates mislabeling errors. The ISME Journal 5: 570-573. (2011). 

Caporaso J. G., Kaczynski J., Stombaugh J., Bittinger K., Bushman F. D., Costello E., Fierer N., Gonzales Pena A., Goodrich J. K., Gordon J. I., Huttley G. A., Kelley S. T., Knights D., Koenig J. E., Ley R. E., Lozupone C., McDonald D., Muegge B., Pirrung M., Reeder J., Sevinsky J. R., Turnbaugh P. J., van Treuren W., Walters W. A., Widmann J., Yatsunenko T., Zaneveld J. and Knight R.: QIIME allows integration and analysis of high-throughput community sequencing data. Nature Methods 7:335-336. (2010).