Radiation induces proinflammatory dysbiosis: transmission of inflammatory susceptibility by host cytokine induction. Issue 1 (24th April 2017)

• Record Type: Journal Article
• Authors: Gerassy-Vainberg, Shiran; Blatt, Alexandra; Danin-Poleg, Yael; Gershovich, Katya; Sabo, Edmond; Nevelsky, Alex; Daniel, Shahar; Dahan, Aviva; Ziv, Oren; Dheer, Rishu; Abreu, Maria T; Koren, Omry; Kashi, Yechezkel; Chowers, Yehuda
• Is Part Of: Gut. Volume 67:Issue 1(2018)
• Page Start: 97
• Page End: 107
• Publication Date: 2017-04-24
• Subjects: RADIATION THERAPY -- INFLAMMATION -- COLONIC MICROFLORA -- CYTOKINES; Gastroenterology -- Periodicals; 616.33
• DOI: 10.1136/gutjnl-2017-313789
• Languages: English
• ISSNs: 0017-5749

Abstract

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. 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.