Gut microbiome-epithelium crosstalk: Fine-tuning local and systemic immunity

The community of resident microbes in the human gut, known as the gut microbiota, is now appreciated to contribute to numerous aspects of human health. Although recent efforts have focused on identifying members of this microbial community and their associations with different diseases, few have explored the mechanisms by which their metabolites interact with host cells to mediate their beneficial or harmful effects. To move beyond taxonomic correlations and enable mechanistic investigation, my research group recently developed numerous biological and bioinformatic tools to map and experimentally test the functional capabilities of gut bacteria. My proposed research will now utilise these new resources alongside my expertise in gut epithelial and immune cell biology and cutting-edge multi-omic analyses to elucidate microbiome-epithelium functions and: 1) Define how gut microbiota metabolites affect host epithelial barrier integrity to resist enteric infection and modulate local and systemic immune cell activation. 2) Dissect how microbiota metabolites control epithelial antigen presentation to contribute to T cell function in local gut inflammation and systemic anti- tumour immunosurveillance. By paving the way to understanding the fundamental molecular mechanisms underpinning the key host-microbiome interactions that drive immunity, our multi-disciplinary functional approach to microbiome research will facilitate the rational design of microbiome-based therapies.