Combining genotoxic gut bacterial strains increases tumor burden and accelerates onset in a germ-free mouse model of colon carcinogenesis.

To identify causal links between gut microbes and tumorigenesis, we colonized germ-free, colon tumor-susceptible mice (ApcMin/+;Il10-/-) with 19 cultured human fecal microbiotas from healthy individuals and patients with inflammatory bowel disease or colorectal cancer. Colonic tumor counts vary by donor microbiota but not by donor health status. In vitro screens of host cell proliferation, genotoxicity, and inflammation in bacteria-mammalian cell co-cultures reveal that genotoxicity best predicts tumorigenic microbes in vivo, with genotoxic microbes present in all tested individuals. The genotoxic subset of strains from each donor induces more tumors than the complete community-even when the complete community is not tumorigenic. Combining genotoxic microbes from multiple sources increases tumor number and decreases time to tumor onset. Together, these results suggest that most individuals harbor genotoxic bacterial strains and that the balance of genotoxic to protective strains determines the timing and severity of tumorigenesis in vivo.