Grant: Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships

The microorganisms inhabiting your gut, your microbiota, have a profound impact on your health, influencing the immunity and metabolism of the host, while providing a barrier to infection. Harbouring a healthy gut microbiota is key to maintaining a functional immune system and metabolism. However dysfunction of this gut microbial environment can result in detrimental effects to the host, including chronic inflammation, malnutrition and diarrhea. Malnutrition specifically is responsible for one-fifth of all deaths in children under 5 years of age. A long recognized but poorly understood condition called environmental enteropathy has now been recognized as a major contributor to the worldwide problem of malnutrition. Environmental enteropathy (EE) is highly prevalent with as many as 70% of children who were raised in developing countries displaying symptoms relating to the disorder. This is a disease of the small intestine, where intestinal dysfunction may result in diminished nutrient uptake, adversely effecting growth and physical development. Despite its widespread incidence, the underlying cause of the disease remains elusive and no animal models exist to study it. We hypothesize that EE is caused by the presence of a sustained oral acquisition of fecal-associated bacteria able to colonize the small intestine, leading to small intestinal bacterial overgrowth and ultimately exacerbating symptoms of malnutrition. The aim of this study is to create a novel mouse model mimicking this condition, enabling the study of the small intestinal environment without the need for biopsy studies in humans, which are invasive and infrequent. By combining the most advanced experimental approaches to study microbe-host interactions, we propose to decipher the mechanisms of what causes EE. In accomplishing the aims of our study, we will be able to better understand the disease mechanisms and screen potential therapeutic interventions to reverse symptoms of malnutrition worldwide.