Trimethylamine-N-oxide as One Hypothetical Link for the Relationship between Intestinal Microbiota and Cancer - Where We Are and Where Shall We Go?

Previous epidemiological studies had provided evidence for a link between the microbial dysbiosis and cancer, particularly colorectal cancer (CRC), yet the molecular basis of this link remains elusive. Recently, the association between plasma levels of trimethylamine-N-oxide (TMAO), an oxidised form of trimethylamine (TMA), and risks of various cancers was demonstrated. The discovery could potentially provide an alternative explanation for the aforementioned link, as TMA production is attributed to intestinal bacteria. Current evidence suggests that inflammation could be a potential molecular mechanism to explain the link between TMAO and cancer, although other mechanisms such as oxidative stress, DNA damage and disruption in protein folding might also play a role. This mini-review article first provides an overview of the current evidence for the association between TMAO and certain cancer types, and the potential mechanisms that could explain their association. Thereafter, the direction of further research on the connection between the intestinal microbiota, TMAO and cancer is suggested.