Grant: CIHR Fellowship

Our gut is home to trillions of microbes, called the microbiota, that engage in a symbiotic relationship with our body's immune system to maintain health. Disruption of the gut microbiota, or "dysbiosis," is linked to the development of immune system dysfunction and diseases, including susceptibility to infections. Nowhere is this more relevant than in the intensive care unit (ICU), where critically ill patients battle life-threatening infections as a result of impaired immune defenses. Recent research has discovered that critically ill patients in the ICU develop severe dysbiosis of their gut microbiota, but how this impacts immune defenses and the development of hospital-acquired infections is poorly understood. Therefore, we propose a comprehensive study of how gut microbiota dysbiosis impacts immune defenses against infections during critical illness. Our study will investigate this important clinical question in both critically-ill patients, as well as cutting-edge animal models with "designer microbiota." We will systematically identify microbiota species that control the balance between immune defense and infection, characterize the mechanisms of microbiota-immune interactions, and test the therapeutic potential of rationally-designed microbiota reconstitution to augment protection against infection in models of critical illness. Overall, this research will advance our understanding of how changes to the microbiota impact host defense, and will create new knowledge to drive therapeutic innovations that harness the microbiota for the treatment of critically ill patients in the ICU.