Exploring the mechanisms of protective effect of high-energy X-ray FLASH radiotherapy on intestine through multi omics analysis

作者：Huan Du, Binwei Lin, Yihan Zhu, Xiaofei Hao, Mingming Tang, Wei Wu, Decai Wang, Yiwei Yang, Yuwen Liang, Wenqiang Tang, Haonan Xu, Jie Li, Feng Gao, Xiaobo Du · 发表于：Radiation Oncology · 年份：2025 · DOI：10.1186/s13014-025-02763-z · 被引用次数：2 · 研究领域：Effects of Radiation Exposure、Radiation Therapy and Dosimetry、Heat shock proteins research

BACKGROUND: The aim of this study is to investigate the potential mechanisms underlying the protective effects of high-energy X-ray FLASH radiotherapy (FLASH-RT) on intestine through multi-omics analysis. METHODS: This study utilized syngeneic colon carcinoma mouse models of CT26 and MC38 to evaluate the therapeutic efficacy of FLASH-RT versus conventional dose rate radiotherapy (CONV-RT) by monitoring survival, tumor size, and body weight. Furthermore, healthy C57BL/6 female mice received whole-abdominal irradiation with either FLASH-RT, CONV-RT, or sham irradiation to compare differences in normal tissue protection. 72 h post-irradiation, intestinal contents from mice were collected for metagenomic analysis, and intestinal tissue was harvested for non-targeted metabolic and single-cell sequencing analyses. RESULTS: In CT26 and MC38 models, both CONV-RT and FLASH-RT have demonstrated similar anti-tumor efficacy. Compared with CONV-RT, whole-abdominal FLASH-RT significantly alleviated acute intestinal injury in mice, as evidenced by better preservation of crypt numbers and villus architecture in the FLASH group. Metagenomic analysis revealed that the relative abundance of the gut-protective bacterium Ligilactobacillus ruminis was significantly higher in the FLASH group than in the CONVgroup. Non-targeted metabolomic profiling identified 34 differential metabolites, of which 29 were upregulated and 5 were downregulated in the FLASH group. Notably, the abundance of 2-hydroxyglu...