Project 467103

The human colonic microbiome is composed of a diverse range of microorganisms (e.g. bacteria, viruses, fungi) which significantly influence human health and disease. These microbiota collectively produce an abundance of metabolites, some of which may promote the alteration of host cell gene expression and lead to the onset and development of various diseases, including colorectal cancer (CRC). CRC is the third most common cause of cancer related deaths worldwide, representing a significant global issue. One factor thought to exacerbate CRC progression is diet, whereby a protein-rich diet may promote cancer-causing microbes to flourish and produce metabolites that progress CRC pathogenesis. As a result, characterizing the colonic microbial metabolic output of both CRC patients and controls under various dietary cues will allow insight into how diet influences CRC progression.I hypothesize that the colonic microbiomes of CRC patients, as compared to controls, will produce metabolites that progress CRC development, especially in response to a high-protein diet. My first objective is to culture the microbial composition in colonic biopsies of both CRC patients and healthy controls using a bioreactor model. My second objective is to characterize the metabolites produced by the colonic microbiomes of CRC patients and controls, in response to both high-protein and high-fibre diets fed to the bioreactor system. Subsequently, metabolite solutions will be applied to human colonic organoid cells to assess the gene expression profiles of these cells and their association to CRC, both before and after dietary exposure. This research will allow for a deepened understanding of dietary impact on colonic microbiota and will aid in developing potential treatment strategies for CRC.