Prior exposure to microplastics heightened the susceptibility of small intestine to radiation-induced injury in C57BL/6 mice.

Microplastics (MPs) have been detected in multiple human organs, raising concerns about their potential health risks. The intestinal tract is particularly vulnerable to MPs exposure and accumulation. Radiotherapy often causes side effects such as radiation-induced intestinal injury (RIII). Although previous studies have shown that MPs exacerbate RIII by altering gut microbiota, their effect on the small intestine's intrinsic sensitivity to radiation remains unclear. In this study, C57BL/6 mice were preexposed to MPs for a short period and then irradiated with 4 or 10 Gy to evaluate intestinal injury. Proteomic analysis of small intestine was performed to identify changes in protein expression. Short-term MPs exposure alone caused minimal intestinal damage. While 4 Gy irradiation did not cause significant intestinal injury, 10 Gy irradiation induced pronounced inflammation, increased epithelial apoptosis, and disrupted villus and lamina propria architecture. Importantly, the mice preexposed to MPs exhibited significantly increased sensitivity to RIII. Furthermore, prior MPs exposure significantly exacerbated RIII at 4 Gy but had no obvious influence on RIII at 10 Gy in C57BL/6 mice. The reason might be that the severe radiation-induced injury caused by 10 Gy could obscure the additional effects of prior MPs exposure. Proteomic analysis implicated the 'PI3K-Akt signaling' pathway as a key mediator of this effect. Indeed, treatment with a PI3K inhibitor could attenuate the MPs-driven susceptibility of small intestine to radiation. These findings underscore the need to minimize MPs exposure in patients undergoing radiotherapy.