Heat Killed Salmonella typhimurium protects intestine against radiation injury through Wnt signaling pathway

Abstract

Purpose: Gastrointestinal (GI) toxicity caused by ionizing radiation (IR) appears to be a limited factor in radiotherapy and a great threat for soldiers on nuclear-related military missions. However, there are currently no approved medical strategies to effectively prevent or mitigate the damage on intestine induced by IR. The present study aimed to elucidate the protective activity of Heat Killed Salmonella typhimurium (HKST) on intestine against ionizing radiation exposure. Materials and Methods: Mouse intestinal crypts and intestinal organoids were isolated from C57BL/6J mice. Mice and HIEC cells were exposed to 60Co γ‐radiation. The dosage was set as following: whole body radiation of 8 Gy; mouse intestinal organoids were irradiated with 0 Gy, 4 Gy, and 6 Gy of γ-rays at dose rate of 1 Gy/min. Cells or mice were pretreated with Heat Killed Salmonella typhimurium (HKST) (107 cells/mice) at 12 hours prior to irradiation.Results: By culturing mouse intestinal organoids and employing whole body irradiation of mice, we found that the radiation-induced damage on intestine was dramatically mitigated by pretreating with HSKT in vitro and in vivo, in which the structure of intestinal organoids and small intestine of the HKST-treated group was more integrated than of the radiation damage group, and HKST pretreatment remarkably promoted the proliferation of intestinal cells post IR exposure (Figure 1 and 2). Further study showed that the radio-protective effects of HKST was involved in DNA damage response (DDR) signaling. Moreover, the stimulation of DDR signaling by HKST upon radiation damage was mediated by Wnt signaling, in which the inhibition of Wnt signaling diminished the radio-protective effects of HKST. Conclusion: Our study demonstrated that Heat Killed Salmonella typhimurium (HKST) could significantly alleviate the damage on intestine induced by IR, and the radio-protective effect of HKST was depended on DDR mediated by Wnt signaling pathway. These findings demonstrated that HKST is a potential bacterium using for the prevention of IR-induced GI toxicity in clinical practice.