This Funding Opportunity Announcement (FOA) encourages innovative multidisciplinary research projects that will advance our mechanistic understanding of microflora influences on Gastro-Intestinal (GI) carcinogenesis. Recent advances in our knowledge of GI microflora composition and function have generated a flood of new information, technologies, and capabilities that may for the first time allow mechanistic investigations of very complex, networked host/microbiome interactions on a systems wide scale.This FOA encourages investigators to ingrate this new information into hypothesis-driven studies that can define and validate molecular mechanisms that determine microbe-induced carcinogenic outcomes.Applicants may integrate information from existing large data sets, including metagenomic data sets,or may also propose to generate appropriate new data sets, including but not limited to analysis of host and microbial genomes, proteomes, metabalomes, post-translational modifications, secreted signals, and protein-protein interaction data. An additional goal of this program is to encourage collaborative efforts between scientists currently engaged in GI cancer research with those in scientific disciplines that may not otherwise apply their expertise to study cancer etiology and prevention. Investigators particularly from the disciplines of microbiology, microbial ecology, molecular biology, immunology, nutrition sciences, bioinformatics, and computational sciences are encouraged to apply. A value added from stimulating integrated, multidisciplinary experimental approaches may include the discovery of emergent properties of the GI ecosystem that could not be elucidated using either descriptive bioinformatics or molecular studies alone.