New Zealand has one of the highest rates of colorectal cancer (CRC) in the world, with poorer outcomes in Māori and Pacific peoples. This study will investigate the link between the microorganisms living in our gut (the microbiome) and the vital host mechanisms involved in CRC development. We will use a combination of nucleic acid sequencing of patient tissue cohorts and in vitro mechanistic studies to investigate the microbiome and host molecular interactions that contribute to the development of CRC, and response to therapy in the treatment of CRC. The outcomes of this study will lead to the development of more sensitive early detection of CRC, and microbiome-based predictive tests that will improve stratification of patients for CRC treatment. The translational impact of this research programme will ultimately lead to a decrease in incidence and improved survival for CRC patients in New Zealand, reducing inequity for Māori and Pacific people.