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

Authors

Tamar Plitt, Alix Piessevaux, Urvija Rajpal, Jeremy Fischer, Matthew P Spindler, Constantin Ruprecht, Zhihua Li, Ilaria Mogno, Ye Yang, A Nicole Desch, Gerald Chu, Zhengyu Jiang, Jianyao Wang, Dirk Gevers, David Pocalyko, Abby L Geis, Christian Jobin, Kurtis E Bachman, Cynthia L Sears, Graham J Britton, Lani R San Mateo, Jeremiah J Faith

Published in

Cell reports. Volume 45. Issue 7. Pages 117645. Jul 07, 2026. Epub Jul 07, 2026.

Abstract

To identify causal links between gut microbes and tumorigenesis, we colonized germ-free, colon tumor-susceptible mice (Apc^Min/+;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.

PMID:
42412611
Bibliographic data and abstract were imported from PubMed on 08 Jul 2026.

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