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Defining the complex role of the microbiome in colorectal cancer (CRC) and the discovery of novel, pro-tumorigenic microbes are areas of active investigation. In the present study, culturing and reassociation experiments revealed that toxigenic strains of Clostridioides difficile drove the tumorigenic phenotype of a subset of CRC patient-derived mucosal slurries in germ-free ApcMin/+ mice. Tumorigenesis was dependent on the C. difficile toxin TcdB and was associated with induction of Wnt signaling, reactive oxygen species, and pro-tumorigenic mucosal immune responses marked by infiltration of activated myeloid cells and interleukin-17 (IL-17)-producing lymphoid and innate lymphoid cell subsets. These findings suggest that chronic colonization with toxigenic C. difficile is a potential driver of CRC in patients.
Julia L Drewes,Jie Chen,Nicholas O Markham
Cynthia L Sears
Julia L Drewes,Jie Chen,Nicholas O Markham,Reece J Knippel,Jada C Domingue,Ada J Tam,June L Chan,Lana Kim,Madison McMann,Courtney Stevens,Christine M Dejea,Sarah Tomkovich,John Michel,James R White,Fuad Mohammad,Victoria L Campodonico,Cody N Heiser,Xinqun Wu,Shaoguang Wu,Hua Ding,Patricia Simner,Karen Carroll,Martha J Shrubsole,Robert A Anders,Seth T Walk,Christian Jobin,Fengyi Wan,Robert J Coffey,Franck Housseau,Ken S Lau,Cynthia L Sears