Combined challenge of mice with Citrobacter rodentium and ionizing radiation promotes bacterial translocation

Abstract

Purpose: Both enteric infection and exposure to ionizing radiation are associated with increased intestinal permeability. However, the combined effect of irradiation and enteric infection has not been described. We combined infection of mice with the enteric pathogen, Citrobacter rodentium, with exposure to ionizing radiation and assessed the impact on colonic epithelial ion transport, permeability and bacterial translocation.

Materials and methods: Mice were infected with C. rodentium and then received whole-body exposure to 5 Gray γ-radiation 7 days later. Three days post-irradiation, mice were euthanized and colons removed. Control groups included sham-infected mice that were irradiated and mice that were infected, but not irradiated.

Results: Macroscopic damage score and colonic wall thickness were increased by C. rodentium infection, but these parameters were not exacerbated by irradiation. Infection caused an increase in myeloperoxidase activity that was reduced by irradiation. Irradiation reduced the secretory response to electrical field stimulation, forskolin and carbachol; these changes were not altered by infection with C. rodentium. None of the treatments caused an increase in permeability to ⁵¹Cr-ethylenediaminetetraacetic acid (EDTA). However, combined infection and irradiation synergistically increased bacterial translocation to mesenteric lymph nodes, liver, spleen and blood.

Conclusions: Although the combination of irradiation and infection did not exacerbate the individual effects of these challenges on ion secretion and mucosal permeability to ⁵¹Cr-EDTA, it dramatically increased susceptibility to bacterial translocation and bacteremia. These results have important implications for patients who develop an enteric infection during the course of abdominopelvic radiotherapy.

Keywords:

• Epithelium
• barrier
• permeability
• infection
• colon