Grant: Project Grant

Colorectal cancer (CRC) is the 2nd most commonly diagnosed cancer in Canada, with an average of 72 Canadians being diagnosed with CRC every day. A link between red meat consumption and the development of CRC has been documented by many studies, and has been partially attributed to the presence of heme in the red meat. Heme, an essential part of the protein hemoglobin, is an iron-containing molecule that serves to bind oxygen. An important role in the development of CRC has also been attributed to the gut microbiota, the complex community of microorganisms, mainly bacteria, that live in the digestive tract. Because bacteria compete for iron, an essential metal indispensable for their growth, and not all bacteria are equipped with the necessary tools to capture and utilize heme iron, we think that heme may change the gut microbiota composition by promoting the growth of certain bacteria over others and cause a bacterial imbalance (dysbiosis). We have generated preliminary results suggesting that dietary heme induces dysbiosis, aggravates inflammation of the colon (colitis, as seen in Inflammatory Bowel Disease), and promotes CRC development in rodents. The overall goal of our research is to determine the role and the mechanisms by which dietary heme modulates the gut microbial composition. In addition, we will test different strategies based on natural and engineered probiotics to reverse the non-beneficial effects of heme-induced microbiota shifts. The high incidence of CRC in Canada compared to other countries has increased the need for preventive measurements, for which it is critical to understand contributing mechanisms. This project will further our understanding of the link between heme, microbiota, and CRC, and how to reverse gut microbiota imbalances (dysbiosis), opening novel avenues for CRC prevention. This project builds on our team's unique expertise in iron metabolism, microbiology, and bioengineering as well as specialist platforms in the institute.