Preventing bacterial disease using the human gut microbiome (360G-Wellcome-312797_Z_24_Z)

The crisis in antimicrobial resistance (AMR) is upon us with millions of deaths each year associated with resistant bacterial infections. Alternatives to antibiotics are urgently needed. The human gut microbiome naturally protects against bacterial infections, through both bacterial competition and its interactions with host immunity. Our overarching goal is to understand and leverage this natural protection to find new ways to prevent bacterial infections and reduce the need for conventional antibiotics. We will focus on infections caused by members of the Enterobacteriaceae, including E. coli, that colonise the human gut and cause over 30% of all AMR related deaths worldwide. A key challenge is that the gut microbiome contains many interacting bacterial species, which makes it a complex system that is difficult to understand and predict. To tackle this, we will take a highly interdisciplinary approach that combines theoretical ecology, bioinformatics, metabolomics, imaging, evolutionary assays, large-scale experiments with human gut bacteria, and the development of novel vaccines to target key species and influence ecological competition in the microbiome. Our goal is to understand what determines ecological success in the human microbiome and how to rationally shape the microbiome to prevent dangerous infections.