Commensal Viruses Promote Intestinal Stem Cell Regeneration Following Radiation Damage by Inhibiting Hyperactivation of RIG-I and Notch Signals.

IF 14.3 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Xiaotong Zhao, Yu Cai, Yujia Hou, Yanjin Wu, Tingting Wei, Lili Li, Zhaojun Duan, Xinran Lu, Jiahui Meng, Haitao Zhou, Qin Wang, Jinhan Wang, Chang Xu, Liqing Du, Saijun Fan, Feng Wang, Qiang Liu, Yang Liu
{"title":"Commensal Viruses Promote Intestinal Stem Cell Regeneration Following Radiation Damage by Inhibiting Hyperactivation of RIG-I and Notch Signals.","authors":"Xiaotong Zhao, Yu Cai, Yujia Hou, Yanjin Wu, Tingting Wei, Lili Li, Zhaojun Duan, Xinran Lu, Jiahui Meng, Haitao Zhou, Qin Wang, Jinhan Wang, Chang Xu, Liqing Du, Saijun Fan, Feng Wang, Qiang Liu, Yang Liu","doi":"10.1002/advs.202505204","DOIUrl":null,"url":null,"abstract":"<p><p>Radiation-induced intestinal injury is a common complication of abdominopelvic cancer radiotherapy, often associated with gut bacteriome dysbiosis. However, the involvement of gut virome in this process remains largely underexplored. Here, it was found that radiation disrupted the gut virome, altered the distribution of phages and their bacterial host. Fecal virome transplantation (FVT) from healthy donors ameliorated radiation-induced intestinal damage and promoted stem cell proliferation by enriching phages targeting Salmonella. Conversely, decreased virome load exacerbated intestinal damage, reduced proliferating stem cells, and impaired secretory lineage differentiation. Mechanistically, exacerbated intestinal injury was associated with hyperactivation of RIG-I and Notch signaling in intestinal stem cells, which was absent in RIG-I-deficient mice. Organoids from RIG-I-deficient mice displayed decreased Notch signals and increased regenerative capacity post radiation. These findings shed light on the intricate interplay between gut virome, intestinal injury, and stem cell responses, highlighting potential therapeutic interventions for targeting the virome to mitigate radiation-induced intestinal damage.</p>","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e05204"},"PeriodicalIF":14.3000,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Advanced Science","FirstCategoryId":"88","ListUrlMain":"https://doi.org/10.1002/advs.202505204","RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0

Abstract

Radiation-induced intestinal injury is a common complication of abdominopelvic cancer radiotherapy, often associated with gut bacteriome dysbiosis. However, the involvement of gut virome in this process remains largely underexplored. Here, it was found that radiation disrupted the gut virome, altered the distribution of phages and their bacterial host. Fecal virome transplantation (FVT) from healthy donors ameliorated radiation-induced intestinal damage and promoted stem cell proliferation by enriching phages targeting Salmonella. Conversely, decreased virome load exacerbated intestinal damage, reduced proliferating stem cells, and impaired secretory lineage differentiation. Mechanistically, exacerbated intestinal injury was associated with hyperactivation of RIG-I and Notch signaling in intestinal stem cells, which was absent in RIG-I-deficient mice. Organoids from RIG-I-deficient mice displayed decreased Notch signals and increased regenerative capacity post radiation. These findings shed light on the intricate interplay between gut virome, intestinal injury, and stem cell responses, highlighting potential therapeutic interventions for targeting the virome to mitigate radiation-induced intestinal damage.

共生病毒通过抑制rig - 1和Notch信号的过度激活促进辐射损伤后肠道干细胞再生
辐射引起的肠道损伤是腹腔盆腔癌放疗的常见并发症,通常与肠道菌群失调有关。然而,肠道病毒在这一过程中的参与在很大程度上仍未被充分探索。在这里,人们发现辐射破坏了肠道病毒群,改变了噬菌体及其细菌宿主的分布。来自健康供体的粪便病毒移植(FVT)可改善辐射诱导的肠道损伤,并通过富集靶向沙门氏菌的噬菌体促进干细胞增殖。相反,病毒载量的降低加重了肠道损伤,减少了增殖干细胞,并损害了分泌谱系分化。机制上,肠道损伤加剧与肠道干细胞中RIG-I和Notch信号的过度激活有关,而在RIG-I缺陷小鼠中则不存在这种情况。rig - i缺陷小鼠的类器官在辐射后显示Notch信号减少和再生能力增加。这些发现揭示了肠道病毒组、肠道损伤和干细胞反应之间复杂的相互作用,强调了针对病毒组减轻辐射诱导的肠道损伤的潜在治疗干预。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Advanced Science
Advanced Science CHEMISTRY, MULTIDISCIPLINARYNANOSCIENCE &-NANOSCIENCE & NANOTECHNOLOGY
CiteScore
18.90
自引率
2.60%
发文量
1602
审稿时长
1.9 months
期刊介绍: Advanced Science is a prestigious open access journal that focuses on interdisciplinary research in materials science, physics, chemistry, medical and life sciences, and engineering. The journal aims to promote cutting-edge research by employing a rigorous and impartial review process. It is committed to presenting research articles with the highest quality production standards, ensuring maximum accessibility of top scientific findings. With its vibrant and innovative publication platform, Advanced Science seeks to revolutionize the dissemination and organization of scientific knowledge.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信