Environmental contaminant activation by the microbiota triggers carcinogenesis. Procarcinogen activation

A high proportion of cancer burden is attributable to exposure to environmental pollutants, many of which, induce carcinogenesis after metabolic activation. Most host enzymes facilitate the elimination of xenobiotics via conjugation reactions. On the other hand, the role of gut microbiota in xenobiotic-induced extraintestinal carcinogenesis has not been thoroughly investigated, although it which encodes 150-fold more genes than the human genome., in xenobiotic-induced extraintestinal carcinogenesis has not been thoroughly investigated. In this study, we took advantage of the mouse bladder cancer model which is well-established to be induced by butyl(3-carboxypropyl)nitrosamine (BCPN), the carcinogenic metabolite of the environmental pollutant N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN), butyl(3-carboxypropyl)nitrosamine (BCPN), to gain insights into the role of gut microbiota in bladder cancer development and the underlying mechanism. This is the first study demonstrating the requirement of gut microbiota mediated carcinogen production in inducing extraintestinal carcinogenesis.