{"title":"Electron-beam FLASH whole brain irradiation induced a unique changes of intestinal flora.","authors":"Feifei Gao, Wei Cheng, Yanxi Ma, Boyi Yu, Xinle Lang, Xiaodong Jin, Jianxin Wang, Xianhong Liu, Cuixia Di, Hui Wang, Fei Ye, Ting Zhao, Weiqiang Chen, Qiang Li","doi":"10.1186/s10020-024-01053-w","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Whole-brain radiotherapy (WBRT) is an important way to treat multiple metastases. Ultra-high dose rate (FLASH) can avoid neurotoxicity caused by conventional irradiation, it has attracted much attention. This study aims to study the difference of irradiation-induced intestinal flora between conventional dose rate and FLASH WBRT.</p><p><strong>Methods: </strong>WBRT with 10 Gy was performed with electron-beam conventional irradiation (2 Gy/s) and electron-beam FLASH (eFLASH) irradiation (230 Gy/s). The intestinal feces and whole brain of mice were isolated after behavioral evaluation at 1st, 3rd and 10th weeks post-irradiation. HE staining and immunofluorescence were used to access the level of brain damage. The differences in intestinal microbes and transcription levels were detected by 16S rRNA gene sequencing and transcriptome sequencing, respectively.</p><p><strong>Results: </strong>eFLASH irradiation significantly reduced radiation neurotoxicity and had a long-term protective effect on cognitive function and learning and memory ability. Compared with conventional irradiation, eFLASH irradiation not only up-regulated the expression of genes related to neuronal regeneration and digestive system, but also induced more abundant intestinal microflora, especially the \"probiotics\" such as Lachnospiraceae and others, which were proved to play a role in radiation protection, increased significantly after eFLASH irradiation. The up-regulated microbiota after eFLASH irradiation was significantly positively correlated with genes related to neuronal development and regeneration, while significantly negatively correlated with genes related to inhibitory synapses. Additionally, conventional irradiation down-regulated microbial metabolism-related pathways, while FLASH did not.</p><p><strong>Conclusions: </strong>In summary, we explored the unique gut microbiota changes induced by eFLASH WBRT for the first time, providing a theoretical basis for exploring the mechanism of action of FLASH.</p>","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"31 1","pages":"165"},"PeriodicalIF":6.0000,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12049017/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s10020-024-01053-w","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Whole-brain radiotherapy (WBRT) is an important way to treat multiple metastases. Ultra-high dose rate (FLASH) can avoid neurotoxicity caused by conventional irradiation, it has attracted much attention. This study aims to study the difference of irradiation-induced intestinal flora between conventional dose rate and FLASH WBRT.
Methods: WBRT with 10 Gy was performed with electron-beam conventional irradiation (2 Gy/s) and electron-beam FLASH (eFLASH) irradiation (230 Gy/s). The intestinal feces and whole brain of mice were isolated after behavioral evaluation at 1st, 3rd and 10th weeks post-irradiation. HE staining and immunofluorescence were used to access the level of brain damage. The differences in intestinal microbes and transcription levels were detected by 16S rRNA gene sequencing and transcriptome sequencing, respectively.
Results: eFLASH irradiation significantly reduced radiation neurotoxicity and had a long-term protective effect on cognitive function and learning and memory ability. Compared with conventional irradiation, eFLASH irradiation not only up-regulated the expression of genes related to neuronal regeneration and digestive system, but also induced more abundant intestinal microflora, especially the "probiotics" such as Lachnospiraceae and others, which were proved to play a role in radiation protection, increased significantly after eFLASH irradiation. The up-regulated microbiota after eFLASH irradiation was significantly positively correlated with genes related to neuronal development and regeneration, while significantly negatively correlated with genes related to inhibitory synapses. Additionally, conventional irradiation down-regulated microbial metabolism-related pathways, while FLASH did not.
Conclusions: In summary, we explored the unique gut microbiota changes induced by eFLASH WBRT for the first time, providing a theoretical basis for exploring the mechanism of action of FLASH.
期刊介绍：
Molecular Medicine is an open access journal that focuses on publishing recent findings related to disease pathogenesis at the molecular or physiological level. These insights can potentially contribute to the development of specific tools for disease diagnosis, treatment, or prevention. The journal considers manuscripts that present material pertinent to the genetic, molecular, or cellular underpinnings of critical physiological or disease processes. Submissions to Molecular Medicine are expected to elucidate the broader implications of the research findings for human disease and medicine in a manner that is accessible to a wide audience.
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