Grant: Early Career Investigator Awards

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 develop extreme dysbiosis of their gut microbiota, which is linked to the development of hospital-acquired infections. This represents a major clinical problem in the care of critically-ill patients, because hospital-acquired infections are unacceptably common (affecting up to 40% of patients), and exceedingly deadly in the ICU (20-25% mortality rate). The ability to therapeutically modify the gut microbiota holds great promise to reduce the burden of infections in the ICU, but we are currently limited by a lack of understanding about how the microbiota regulates immune function during critical illness. Therefore, we will directly address this problem by performing a comprehensive study to discover how dysbiosis of the gut microbiota induces immune dysfunction in critical illness. Our research will investigate this important clinical question in both critically-ill patients, as well as cutting-edge animal models with "designer microbiota." Furthermore, we will translate our findings into innovative treatment strategies that use precision-editing of the gut microbiota to correct dysbiosis-induced immune dysfunction to restore host defense against infections. Together, this research will advance our understanding of microbiota-immune interactions in critical illness, and deliver novel therapeutic innovations to combat the scourge of infection-related morbidity and mortality in the intensive care unit.