In a recent review by Slater Clay and other OPTIMISTICC team members, titled Colorectal cancer: the facts in the case of the microbiota they review the microbiome’s relevance in the initiation and progression of colorectal cancer (CRC). Noting that it is increasingly appreciated but defining how microorganisms influence susceptibility to and progression of cancer remains a challenge.  They evaluate three CRC-correlating bacteria, colibactin-producing Escherichia coli, enterotoxigenic Bacteroides fragilis, and Fusobacterium nucleatum, for their virulence features relevant to CRC. They also consider the beneficial bioactivity of gut microbes by highlighting a microbial metabolite that may enhance CRC antitumor immunity. In doing so, they aim to elucidate unique and shared mechanisms underlying the microbiota’s contributions to CRC and to accelerate investigation from target validation to CRC therapeutic discovery.