Colorectal cancer is the third most common cancer in both men and women in the United States. There is growing evidence that pathogenic alterations in the composition of the gut microbiome, also known as dysbiosis, can disrupt intestinal homeostasis, promote inflammation, and increase susceptibility to cancer. In contrast, in the absence of dysbiosis, the gut microbiota largely benefit the host, such as by promoting the development of the gut immune system, facilitating dietary metabolism, and preventing pathogen colonization. However, the function of specific members of the gut microbiota and the mechanism by which the gut microbiota modulates tumor susceptibility have not been clearly defined. Based on our preliminary data, our central hypothesis is that a limited number of bacterial species is capable of reducing colon cancer risk. The purpose of our proposed studies is to further our understanding of the mechanism by which commensal bacteria modulate colon cancer risk using mice models complemented by metabolomics and proteomics. Our long-term goal is to develop a probiotic cocktail of human commensal bacteria that can be used to reduce risk of developing colon cancer, particularly in high risk populations, such as patients with inflammatory bowel disease, familial adenomatous polyposis, or recurrent adenomas.