Grant: Project Grant

Colorectal cancer (CRC) is the second leading cause of cancer-related deaths in Canada. Although significant efforts have been employed to understand the etiology of this cancer, the cause of this cancer is still unknown. Recent work has linked bacteria that reside in the gut to CRC, specifically, certain so-called "pathobionts", which are symbiotic members of the gut microbiota that can participate in disease under pathological conditions. Indeed, the list of pathobionts that cause CRC is growing, yet their oncogenic mechanisms are only beginning to be understood. To understand the role of the pathobionts in CRC, we have assessed whether pathobionts cross-talk with other etiologic factors to promote CRC. Indeed, we recently showed that a specific E.coli bacteria that is found in up to 20% of healthy individuals can promote CRC when mice are fed a widely popular weight reducing diet that is low in carbohydrates and fibers. In addition, we show that this E.coli bacteria can promote CRC in mice harbouring mutations in a DNA repair gene that is commonly mutated in CRC patients. In short, our work is beginning to uncover the mechanisms by which pathobionts interact with specific etiologic factors to promote cancer. Using these animal models, we are now in position to dissect the mechanisms of how different factors promote CRC and develop protocols to reduce CRC incidence in pre-clinical models. In addition, we will test whether other similar E.coli bacteria, including a probiotic strain, can promote CRC in preclinical models. This work will inform new strategies related to dietary and lifestyle modifications, screening high-risk individuals, and personalizing the treatment modalities that could be employed in CRC prevention and therapy.