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.