The effects of myeloablative or non-myeloablative total body irradiations on intestinal tract in mice
Acute radiation injury caused by high-dose radiation exposure severely impedes the application of radiotherapy in cancer management. To deeply understand the side effects of radiation on intestinal tract, an irradiation murine model was applied and evaluated. C57BL/6 mice were given 4Gy non-myeloablative irradiation, 8Gy myeloablative irradiation and non-irradiation (control), respectively. Results demonstrated that the 8Gy myeloablative irradiations significantly damaged the gut barrier along with decreasing MECA32 and ZO-1. However, a slight increase of MECA32 and ZO-1 was detected in the 4Gy non-myeloablative irradiations treatment from day 5 to day 10. Further, the irradiations affected the expression of P38 and JNK MAPK but not ERK1/2 MAPK signal pathway. Moreover, irradiation had adverse effects on hematopoietic system, altered the numbers and percentages of intestinal inflammatory cells. The IL-17/AhR had big increase in the gut of 4Gy irradiation mice at day 10 compared with other groups. Both 8Gy myeloablative and 4Gy non-myeloablative irradiation disturbed the levels of short chain fatty acids in intestine. Meanwhile, high dosage of irradiation decreased the intestinal bacterial diversity and altered the community composition. Importantly, the fatty acids generating bacteria Bacteroidaceae and Ruminococcaceae played key roles in community distribution and short chain fatty acids metabolism after irradiation. Collectively, the irradiation induced gut barrier damage with dosages dependent that led to the decreased p38 MAPK and increased JNK MAPK, unbalanced the mononuclear cells of gut, disturbed intestinal bacterial community and short chain fatty acids level.