Grant: Project Grant

Fatty liver disease, scientifically known as metabolic dysfunction-associated steatotic liver disease (MASLD), affects about one in three Canadians and is becoming the leading cause of liver failure, liver cancer, and liver transplantation. One important predictor of poor outcomes in MASLD is scarring of the liver, called fibrosis. However, people with MASLD do not all progress in the same way. Some develop advanced liver damage quickly, while others never do, and there are currently no reliable tools to predict who is at greatest risk. One possible reason for these differences may lie in the gut microbiome, the community of bacteria and other microorganisms that naturally live in our intestines. These microbes can influence how the immune system functions and how liver cells respond to injury. Our research focuses on a specific gut bacterium that, in experimental models, speeds up fatty liver development. We will use specialized germ-free mice and genetically engineered immune cells to learn exactly how this bacterium affects immune responses and liver injury. To ensure our findings are relevant to patients, we will also study stored liver biopsies and stool samples from patients with MASLD. Using advanced spatial technologies, we can map gene activity in specific areas of the liver and link these patterns to the gut bacteria found in each patient. By combining cutting-edge laboratory models with human samples, our work will reveal how gut microbes and the immune system work together to drive fatty liver disease. This knowledge could lead to better ways to identify high-risk patients earlier and develop microbiome-based treatments, expanding the limited options available today.