Leveraging phage infection to decrease pathobiont virulence in inflammatory bowel disease

The makeup of bacterial communities in the gut is strongly linked with inflammatory bowel disease (IBD) including Crohn’s disease and ulcerative colitis. Pathobionts like E. coli are opportunistic pathogens that exacerbate gut inflammation in IBD but respond poorly to antibiotics. Bacteriophages (phages) – highly specific bacterial viruses – can alter gut microbiome composition, and so could be used in IBD treatments. Phages, however, undergo evolution – they change over time in response to their environment. Their safe and effective use in treatments therefore requires an understanding of how they co-evolve with the pathobionts in the gut. Here, I will study E. coli pathobiont and phage co-evolution in the gut in response to malabsorption – a key symptom of IBD that causes high gut osmolality (concentration of molecules). Bacteria can adapt to these changes by regulating osmotic channels, but at a cost: phages use those channels to infect. By combining a computational model of bacteria-phage growth with evolution experiments performed in the gut, I will determine the role played by malabsorption in driving bacteria-phage co-evolution and reducing pathobiont load, in turn informing the development of phage therapies for IBD.