Herein, we will test the hypothesis that individuals with early onset colorectal cancer (EO-CRC) display microbial and colonic epithelial signatures that differ from age-matched controls. In our distinct, but complementary, Specific Aims, we will trace the epidemiology of biofilm formation on CRCs for the past 35 years, test the antibody responses of EO-CRC patients and comparator disease and control groups to biofilm and other microbes and determine if microbial exposures induce changes in colon epithelial biology that lower the threshold for colon epithelial cell neoplastic transformation. Our results will provide insight into the microbial associations and colon epithelial cell mechanisms that we predict potentiate EO-CRC, with the ultimate goal of informing and accelerating novel strategies for EO-CRC detection, prevention and intervention.