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

Gut. 2018 Jan;67(1):97-107. doi: 10.1136/gutjnl-2017-313789. Epub 2017 Apr 24.


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. Increased colonic tumor necrosis factor (TNF)α, IL-1β and IL-6 expression was observed at two different time points. Adherent microbiota from RP differed from those in uninvolved segments and was associated with tissue damage. Using bacterial-epithelial co-cultures, postradiation microbiota enhanced IL-1β and TNFα expression compared with naïve microbiota. GF mice colonisation by irradiated microbiota versus controls predisposed mice to both radiation injury and DSS-induced colitis. IL-1 receptor antagonist administration ameliorated intestinal radiation injury.

Conclusions: The results demonstrate that rectal radiation induces dysbiosis, which transmits radiation and inflammatory susceptibility and provide evidence that microbial-induced radiation tissue damage is at least in part mediated by IL-1β. Environmental factors may affect the host via modifications of the microbiome and potentially allow for novel interventional approaches via its manipulation.


Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Coculture Techniques
  • Colitis / etiology*
  • Colitis / immunology
  • Colitis / microbiology
  • Cytokines / biosynthesis*
  • Disease Susceptibility
  • Dysbiosis / etiology*
  • Dysbiosis / immunology
  • Dysbiosis / microbiology
  • Fecal Microbiota Transplantation
  • Feces / microbiology
  • Female
  • Gastrointestinal Microbiome / radiation effects*
  • Germ-Free Life
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / microbiology
  • Mice, Inbred C57BL
  • Proctitis / etiology
  • Proctitis / immunology
  • Proctitis / microbiology
  • Radiation Injuries / immunology
  • Radiation Injuries / microbiology*
  • Rectum / immunology
  • Rectum / microbiology
  • Rectum / radiation effects


  • Cytokines