INTERNATIONAL GRANT 2020
Gut Microbiota Post Antibiotics or Post Infectious functional Bowel Disorders
Pr Premysl Bercik, Professor of Medicine, Division of Gastroenterology, McMaster University & Gastroenterologist at Hamilton Health Science. Hamilton Ontario, Canada
“Clostridium difficile-induced post-infectious Irritable Bowel Syndrome: Study of the mechanisms and treatments”
We hypothesize that the sustained low-grade inflammation that is triggered by the infection, in combination with antibiotic-induced dysbiosis, lead to the disruption of gut physiology and function, and, later in time, to changes of intestinal morphology.
In order to understand the mechanisms underlying development of gut dysfunction following C. diff infection, we will employ our previously established humanized mouse model of IBS, using fecal microbiota from patients with PI-IBS to colonize germ-free mice. We will analyze human donor and mouse microbiota using molecular techniques to identify and isolate bacteria that are involved in gut dysfunction and inflammation. Using different immunodeficient mice, we will identify specific immune mechanisms underlying gut changes. Finally, we will investigate several possible therapeutic approaches to either prevent development or treat already established gut dysfunction.
Overall, we hope to identify the specific mechanisms underlying development of PI-IBS as well as novel treatments, which will inform future clinical trials in patients.