{"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.
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.