Grant: CIHR Fellowship

Over the past decade, a major focus for research has been on the types of bacteria which, under normal circumstances, reside in the intestinal tract of all mammals. These bacteria are collectively referred to as the microbiota. Disrupting the composition of the microbiota by antibiotic use has been linked to the development of allergic diseases. Mice treated with antibiotics early in life acquire an altered microbiota composition, and exhibit exaggerated inflammation in their airways when they are tested in an experimental model of allergy. I propose to extend these findings, by identifying the key types of bacteria within the microbiota that alter the severity of allergy development in a mouse model. Additionally, I plan to gain insight into the immune mechanisms by which these key bacterial species alter the immune response to allergens, by focusing on how antibody responses are altered in the presence of different intestinal microbiota compositions. High levels of the antibody subtype IgE measured in the blood are associated with allergic asthma development in humans, and antibiotic-treated mice also have elevated IgE levels. Using clinically relevant drugs, I will alter IgE levels in mice, measure how this affects immune cell populations in the intestines and lungs, and test whether this alters sensitization to allergens. I aim to test the hypothesis that a normal, undisrupted microbiota limits IgE production through repressing specific intestinal immune cells. I believe that this project will result in both the identification of specific groups of bacteria which enhance or protect from allergic disease development, and the description of immune mechanisms by which these bacteria act. In the future, antibiotics will continue to be a vital asset to medicine, but if their use is linked to allergy development, it is necessary to understand how this occurs, so that measures can be taken to mitigate these negative effects.