In collaboration with the Luca and Blekhman labs we are seeking to characterize at the molecular level the interaction between the host cells in the gut and the microbiome. The human gut microbiome is becoming increasingly important as a means of understanding inter-individual differences in health status and digestive processes. Specific microbiome profiles have been associated with variation in diet composition, but also with physiological and disease status in the host. Despite these promising examples, the cause-effect relationships between the host and the microbiome are still unclear. Recent studies have shown that host genetic variation is an important factor shaping the composition of the microbiome. In addition, functional genomic studies have investigated the transcriptional response and chromatin landscape changes induced by the microbiome in mice. However, we still know very little about the molecular mechanisms controlling host-microbiome interaction, and how variation in host genetic background and gene regulation affects this interaction, especially in humans. We have recently developed an approach that uses a human cellular model (primary human colonic epithelial cells) and a functional genomics approach to characterize the host regulatory changes determined by interaction with the microbiome in a manner that will elucidate the cause-effect relationships.
This approach is effective in identifying host genetic variants that modulate the response to the microbiome, through allele-specific expression (ASE). We have also shown that it can be used to dissect the expression changes induced by the microbiome in genes associated with human complex traits, including colorectal cancer and obesity.
Read more in our recent paper.