DNA Damage and the Gut Microbiome: From Mechanisms to Disease Outcomes

Both the number of cells and the collective genome of the gut microbiota outnumber their mammalian hosts, and the metabolic and physiological interactions of the gut microbiota with the host have not yet been fully characterized. Cancer remains one of the leading causes of death, and more research into the critical events that can lead to cancer and the importance of the gut microbiota remains to be determined. The gut microbiota can release microbial molecules that simulate host endogenous processes, such as inflammatory responses, or can alter host metabolism of ingested substances. Both of these reactions can be beneficial or deleterious to the host, and some can be genotoxic, thus contributing to cancer progression. This review focused on the molecular evidence currently available on the mechanistic understanding of how the gut microbiota are involved in human carcinogenesis. We first reviewed the key events of carcinogenesis, especially how DNA damage proceeds to tumor formulation. Then, the current knowledge on host DNA damage attributed to the gut microbiota was summarized, followed by the genotoxic endogenous processes the gut microbiota can induce. Finally, we touched base on the association between specific gut microbiota dysbiosis and different types of cancer and concluded with the up-to-date knowledge as well as future research direction for advancing our understanding of the relationship between the gut microbiota and cancer development.