Colorectal cancer: the facts in the case of the microbiota

The importance of the microbiota in the development of colorectal cancer (CRC) is increasingly evident, but identifying specific microbial features that influence CRC initiation and progression remains a central task for investigators. Studies determining the microbial mechanisms that directly contribute to CRC development or progression are revealing bacterial factors such as toxins that contribute to colorectal carcinogenesis. However, even when investigators have identified bacteria that express toxins, questions remain about the host determinants of a toxin’s cancer-potentiating effects. For other cancer-correlating bacteria that lack toxins, the challenge is to define cancer-relevant virulence factors. Herein, we evaluate three CRC-correlating bacteria, colibactin-producing Escherichia coli, enterotoxigenic Bacteroides fragilis, and Fusobacterium nucleatum, for their virulence features relevant to CRC. We also consider the beneficial bioactivity of gut microbes by highlighting a microbial metabolite that may enhance CRC antitumor immunity. In doing so, we 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.