Abstract Background Bacterial contributions to the development of Inflammatory Bowel Diseases (IBD) and colorectal cancer (CRC) are increasingly recognized, yet the molecular mechanisms linking microbial activity to host tumorigenesis remain poorly understood. Methods We combined in vitro epithelial cell assays, mouse models of IBD- and CRC-associated tumorigenesis, in situ immunofluorescent multiplexing and bacterial genetics to investigate how K. pneumoniae and its Type VI Secretion System (T6SS) modulate host signaling and immune responses. Results K. pneumoniae inhibited p53 activity, thereby impairing p53 responses to DNA damage and oncogenic stress and reducing chemotherapy efficacy. On the bacterial side, we identified the T6SS as the major determinant of IBD severity. T6SS activity promotes chronic inflammation and tumorigenesis in IBD/CRC models and reshaped the immune microenvironment toward immunosuppression, including reduced Treg cell abundance. Conclusion These findings reveal that K. pneumoniae T6SS drives tumorigenesis in IBD and CRC through increased inflammation and suppression of the p53 activity. Reference: PMID: 35197571 Conflict of interest: Dr. Aschtgen, Marie-Stéphanie: No conflict of interest
M S Aschtgen (Thu,) studied this question.