Colorectal cancer mouse model displays gut microbiome-dependent sensitivity to pelvic irradiation

Radiotherapy is known to induce gastrointestinal adverse effects including intestinal dysbiosis in colorectal cancer (CRC) patients which can decrease compliance for continued treatment in a subset of patients. In this study, we want to investigate the potential contribution of the initial gut microbiome of CRC patients in relationship to the differential response in sensitivity for irradiation-induced side effects. In this study, colitis-associated CRC mice (AOM/DSS-induced) were subjected to a two week fractionated pelvic irradiation protocol. Post irradiation, quantitative 16S rRNA gene analysis revealed significant gut bacterial dysbiosis. De novo clustering based on the gut bacterial composition of the irradiated mice enabled identification of radiosensitive mice that experienced a rather prolonged bacterial shift post-irradiation versus radioresistant mice that did not. Remarkably, radiosensitive mice had a lower abundance of specific bacterial taxa including Duncaniella muris pre irradiation.In conclusion, the established CRC mouse model enabled the identification of radiosensitive and radioresistant mice. The obtained data illustrate that sensitivity to pelvic irradiation is likely linked to the gut microbial composition prior to radiotherapy. Altogether, our findings highlight the potential to prevent irradiation induced adverse effects in CRC patients by correcting the microbial ecology of the gut