Emerging data have linked the gut microbiome to colorectal adenomas, the established early lesions in colorectal cancer (CRC) and de facto targets during screening colonoscopy. Identification of intervenable hostmicrobiome interactions driving adenoma formation could serve as the basis for biology-backed precision prevention of adenomas and ultimately CRC. The Alaska Native community faces a high burden of CRC, with the highest incidence and mortality rates in the US. The reasons behind this disparity are unclear but may involve geographic challenges to accessing screening colonoscopy and CRC risk imparted by the microbiome. However, data on gut microbiomes in Alaska Natives are scant, and there are no published studies that have reported using metagenomic and/or metabolomic data generated specifically from the Alaska Native population to predict adenomas or CRC. In this Administrative Supplement to Support Cancer Disparity Collaborative Research, we address this through a proposed partnership between our lab at Fred Hutch Cancer Center and Dr. Diana Redwood’s group at Alaska Native Tribal Health Consortium (ANTHC). We will identify gut microbial biomarkers for precancerous colorectal lesions in the Alaska Native population and establish the basis for improved non-invasive screening and investigations into microbiome-based adenoma-preventing interventions.