Radiation induces proinflammatory dysbiosis: transmission of inflammatory susceptibility by host cytokine induction

Abstract

Objective Radiation proctitis (RP) is a complication of pelvic radiotherapy which affects both the host and microbiota. Herein we assessed the radiation effect on microbiota and its relationship to tissue damage using a rectal radiation mouse model. Design We evaluated luminal and mucosa-associated dysbiosis in irradiated and control mice at two postradiation time points and correlated it with clinical and immunological parameters. Epithelial cytokine response was evaluated using bacterial-epithelial co-cultures. Subsequently, germ-free (GF) mice were colonised with postradiation microbiota and controls and exposed to radiation, or dextran sulfate-sodium (DSS). Interleukin (IL)-1β correlated with tissue damage and was induced by dysbiosis. Therefore, we tested its direct role in radiation-induced damage by IL-1 receptor antagonist administration to irradiated mice. Results A postradiation shift in microbiota was observed. A unique microbial signature correlated with histopathology.

Fecal microbiota transplantation in cancer management: Current status and perspectives

“…Radiotherapy is one of the most successful cancer therapies, but it may give rise to severe tissue damage that limits its use. Small intestine epithelium has high sensitivity to radiation and is the major site of radiation‐induced injury due to frequent intestinal epithelial turnover . A shift in intestinal microbiota composition after radiotherapy was observed in mice .…”

The microbiota: an underestimated actor in radiation-induced lesions?

“…The data presented by Gerassy-Vainberg et al 10 are reminiscent of what is observed in IBD in which the dysbiotic microbiota is a strongly suspected actor in disease evolution. Indeed, the radiation-induced dysbiosis described is reminiscent to IBD and to colitis models in mice with notably a decreased abundance in Firmicutes and an increased abundance in Proteobacteria .…”

“…Consequent to dysbiosis, intestinal inflammation in both disease entities (ie, radiation-induced enteritis and IBD) may be partly driven by IL-1 receptor signalling 10 13. Thus, the results presented by Gerassy-Vainberg et al 10 suggest that common mechanism(s) are engaged in intestinal inflammation of different origin which culminate in dysbiosis and consecutive derangements in the host–microbiota crosstalk.…”

“…The results by Gerassy-Vainberg et al 10 pose several questions. (1) Is microbial composition or diversity a reliable predictive marker of radiation-induced lesions?…”

“…In this issue, Gerassy-Vainberg et al 10 demonstrated that radiation-induced dysbiosis promoted susceptibility to radiation-induced injury and intestinal inflammation. In this study, the authors took advantage of a mouse model of radiation that allowed localised injury to the rectum which mimics human radiation proctitis.…”