Pelvic radiotherapy induces proinflammatory dysbiosis

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Pelvic radiotherapy affects the composition of the intestinal microbiota in the irradiated areas This dysbiosis leads to increased inflammatory responses induced by epithelial cytokines.

 

Pelvic radiotherapy is mainly used to treat cancer. Although pointed at the tumor, radiations also damage healthy tissue and cause intestinal dysbiosis, which could play a role in the intensity of local inflammatory response. A team of Israeli researchers proceeded on that assumption in order to better understand the relations between intestinal microbiota, tissue damage and epithelial cytokine response, especially interleukin-bêta (IL-b), which has a significant role in the proinflammatory reaction.

Debilitating dysbiosis

The researchers started by assessing dysbiosis and intestinal cytokine production in rectally irradiated and control mice.  They then studied the impact of radiation exposure or DSS*-induced colitis on germ-free mice which received a fecal microbiota transplant post radiation. Finally, they tested the role of IL-b in radiation-induced damage in these same mice through the administration of IL-b receptor antagonist. First observation: rectal radiations induce the expected tissue dysbiosis in the cancerous area, whereas healthy tissue maintains its original microbial population. Second observation: microbiota dysbiosis is associated with increased local secretion of IL-b (and other cytokines, including TNF-a and IL-6). Last  observation: germ-free mice inoculated with radiation-induced microbiota were  more susceptible to ionizing radiation and DSS, thus suggesting that this radiation-induced dysbiosis is able to relay its proinflammatory signals. Moreover, IL-b inhibition is accompanied by an improvement in the epithelial state, thus confirming the direct link between altered microbiota, secretion of IL-b and postradiation gastrointestinal damages.

Suspected etiology, potential preventive measures

The researchers concluded that rectal radiation induces intestinal dysbiosis, thus exacerbating proinflammatory susceptibility; and that associated tissue damage is, at least partially, mediated by IL-b. Acting on the intestinal microbial environment might be a therapeutic approach worth exploring in order to limit cellular damage and its consequences following pelvic radiotherapy.

 

* DSS = Dextran Sulfate-Sodium: substance used in rodents to induce inflammation of the gastrointestinal tract and produce colorectal tumors.

 

Sources:

Gerassy-Vainberg S, et al. : Radiation induces proinflammatory dysbiosis: transmission of inflammatory susceptibility by host cytokine induction, Gut 2017;0:1–11. doi:10.1136/gutjnl-2017-313789.