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.