Interrogating Immune-bacteriophage Dynamics to Mitigate Intestinal Inflammation.

The human gut is home to trillions of bacteria affecting our health. Even more abundant are viruses that specifically infect these bacteria. These viruses are called bacteriophages and have the ability to control the number and function of the bacteria that live within us. Individuals with inflammatory bowel disease (IBD), such as Crohn’s disease or ulcerative colitis, have an imbalance in their gut bacteria that causes the activation of the underlying immune system, chronic inflammation, and tissue injury. We predict that changing the bacteriophages in the gut of patients with IBD could provide a new therapeutic approach to limit inflammation and disease progression. However, the specific type of bacteriophages that live in the gut and their influence on this important ecosystem are not known. Using mice in which the normal gut microbes have been replaced with bacteria and bacteriophages from healthy individuals or from patients with IBD, we will determine how each of these microbial components contribute to immune dysfunction and susceptibility to animals models of human colitis. Results generated from our work will identify how viruses can be harnessed to ameliorate intestinal inflammation and disease.