The intestinal microbiota in colorectal cancer metastasis - Passive observer or key player?

The association between colorectal cancer (CRC) and alterations in intestinal microbiota has been demonstrated by several studies, and there is increasing evidence that bacteria are an important component of the tumour microenvironment. Bacteria may contribute to the development of CRC metastasis by signalling through metabolites, promoting epithelial-mesenchymal transition, creating an immunosuppressive microenvironment and through the impairment of the gut-vascular barrier. Host immunity and intestinal microbiome symbiosis play a key role in determining innate and adaptive immune responses at the local and systemic level. How this gut-systemic axis might contribute to the development of CRC metastasis is however unclear. Several clinical trials are investigating the impact of microbiome-targeted interventions on the systemic inflammatory response, treatment-related complications, and side effects. This review examines pre-clinical and clinical studies which have examined the role of microbes in relation to CRC metastasis, the mechanisms which may contribute to tumour dissemination, and directions for future work.