Grant: Project Grant

Cholesterol gallstones are one of the most prevalent gastrointestinal conditions in developed countries. They are frequently observed in association with disorders of the metabolic syndrome and constitute an important public health problem that imposes a heavy toll in the quality of life of affected patients and a significant burden to medical systems. In Canada, it is estimated that 10% of women and 20% of men would have developed gallstones by the age of 60. The primary causes of gallstone formation are not fully understood. It is thought that sustained environmental insults (such as high-fat/high cholesterol diets) trigger functional alterations in the liver and the biliary system, which lead to accumulation of solid cholesterol in the gallbladder and disease in genetically predisposed subjects. The aim of our study is to determine whether alterations of the intestinal microbiota and defects on the intestinal barrier that result in increased intestinal permeability (a condition also known as "leaky gut") are environmental factors contributing to the development of cholesterol gallstones. We will use Magnetic Resonance Imaging (MRI) to study the process of cholesterol gallstones formation in response to intestinal injury and increased intestinal permeability, using several animal models. In addition, we will determine alterations in the composition and function of the intestinal microflora in the context of cholesterol gallstone disease and how that may contribute to the development of gallstones. These studies will help to uncover the origins and the molecular mechanisms underlying cholesterol gallstones formation and will generate new knowledge needed for effective prevention or treatment of this prevalent disorder.