Grant: CAG/CCFC/CIHR Summer Studentship for Research in Gastroenterology

Observations of patients with IBD have shown that many of these individuals have increased epithelial permeability and abnormal mitochondria in their enteric epithelial cells: the latter is indicative of metabolic stress and reduced ATP production. Assessing a putative functional relationship between metabolic stress and loss of epithelial barrier function, we have shown that exposure of monolayers of T84 epithelial cells treated with the metabolic stress, dinitrophenol (DNP), in the presence of commensal Escherichia coli display significant perturbations in their barrier properties. In the present study, we continue to use this cell culture model to assess the impact of metabolic stress on mucus synthesis and release: mucus is a key extrinsic component of the epithelial barrier. Understanding how metabolic stress can affect epithelial permeability (in this instance mucus production) such that excess bacteria can cross this cell layer and move into the mucosa is of importance to health and well-being. Thus the applicability of the proposed research is relevant not only to IBD, but to other serious conditions such as sepsis and multi-organ failure which can be fatal and can occur if bacteria resident in the gut lumen breech the epithelial barrier and cross into the body proper.