Lu Haiyan, Xie Liwei, Guo Liangsheng, Gu Xuhao, Zhu Ruiqiu, Yang Yinyin, Tang Fengling, Li Mingyue, Liu Chengzhi, Wang Difan, Li Ming, Tian Ye, Cai Shang
Department of Radiotherapy and Oncology, the Second Affiliated Hospital of Soochow University, Suzhou 215004, China.
Department of Obstetrics and Gynecology, the Second Affiliated Hospital of Soochow University, Suzhou 215004, China.
Radiother Oncol. 2025 Jan;202:110608. doi: 10.1016/j.radonc.2024.110608. Epub 2024 Oct 31.
Radiation-induced intestinal injury (RIII) compromises the clinical utility of pelvic radiotherapy (RT). We aimed to explore the protective effect and underlying mechanism of (-)-epigallocatechin-3-gallate (EGCG) on RIII.
We evaluated the protective effect of EGCG on intestine in RIII mouse model and pelvic cancer patients, while explored the underlying mechanism through (1) 16S rRNA sequencing, (2) metabolomic profiles, (3) fresh sterile fecal filtrate (SFF) transplantation, and (4) transcriptome sequencing.
EGCG efficiently prevented RIII in mouse, as reflected by improved survival, alleviated intestinal structure damage, promoted intestinal regeneration, and ameliorated gut microbiota dysbiosis. Prophylactic EGCG intervention reduced the severity of RIII in patients receiving pelvic RT. Mechanistically, the protective effect of EGCG could be transferred to other mice by SFF transplantation. EGCG enriched gut microbiota-derived metabolite D-tagatose, and oral administration of D-tagatose reproduced the radio-protective effect of EGCG via activating AMPK.
Oral EGCG may be a promising strategy for preventing RIII clinically, and warrant further investigation in prospective randomized phase III trials.
放射性肠损伤（RIII）影响了盆腔放疗（RT）的临床应用价值。我们旨在探讨表没食子儿茶素-3-没食子酸酯（EGCG）对RIII的保护作用及其潜在机制。
我们评估了EGCG对RIII小鼠模型和盆腔癌患者肠道的保护作用，同时通过（1）16S rRNA测序、（2）代谢组学分析、（3）新鲜无菌粪便滤液（SFF）移植和（4）转录组测序来探究其潜在机制。
EGCG有效预防了小鼠的RIII，表现为提高生存率、减轻肠道结构损伤、促进肠道再生以及改善肠道微生物群失调。预防性EGCG干预降低了接受盆腔放疗患者的RIII严重程度。从机制上讲，EGCG的保护作用可通过SFF移植转移至其他小鼠。EGCG使肠道微生物群衍生的代谢物D-塔格糖富集，口服D-塔格糖通过激活AMPK重现了EGCG的放射保护作用。
口服EGCG可能是临床上预防RIII的一种有前景的策略，值得在前瞻性随机III期试验中进一步研究。
