Characterization of the human gut microbiome is becoming increasingly prominent to understand inter-individual differences in health status and digestive processes. Tthe human microbiome can be thought of as a variable local environment for the host cell in the specific body site. Thus host-microbiome interactions can be studied in the general framework of GxE. Our goal is to elucidate the cause-effect of the host-microbiome relationships and how they affect complex trait variation in humans. We are using a human cellular model and functional genomics methods to characterize the host regulatory changes in response to presence of the gut microbiome (Richards et al, 2016, mSystems; Richards et al, 2018, Biorxiv). We are also assembling a panel of microbiome sub-types across host physiological and pathological states (e.g. BMI, colorectal cancer), primate species, and human populations (through the Global Microbiome Conservancy project, http://microbiomeconservancy.org/), that we use to treat the human cells. We aim to identify human regulatory variants contributing to inter-individual variation in the response to the microbiome. These results will help to understand the role of host-microbiome interactions on human complex traits.