{"title":"生酮饮食通过促进肠道微生物衍生丁酸盐的产生来抑制胶质瘤的进展","authors":"Ming-Liang Chen, Ying He, Xun-Hu Dong, Hao-Fei Liu, Ze-Xuan Yan, Xiao-Lu Lu, Qing-Qing Miao, Qing-Ning Zhao, Hang Zhang, Li Luo, Shuai Wang, Jing-Yuan Li, Dong-Fang Xiang, Yong Lin, Tian-Ran Li, Xin-Yue Zhou, Yang-Yang Zhou, Min Mao, Xia Zhang, Hong Wei, Xiu-Wu Bian","doi":"10.1016/j.ccell.2025.09.002","DOIUrl":null,"url":null,"abstract":"The ketogenic diet (KD) is a potential therapeutic strategy for glioma; however, the underlying mechanisms remain unclear. Herein, we first identify that glioma patients exhibit a distinct gut microbial profile characterized by reduced butyrate-producing bacteria abundance, particularly <em>R</em>. <em>faecis</em>, along with decreased butyrate levels. Notably, KD reshapes the gut microbiota especially enriching <em>A</em>. <em>muciniphila</em> in a mucin-2-dependent manner, elevates butyrate production, and activates caspase-3 in microglia. These changes promote an anti-tumor microglial phenotype, ultimately suppressing glioma progression in mice. Crucially, KD’s anti-glioma effect is notably abolished by antibiotics treatment; germ-free condition; or specific depletion of mucin-2, microglia, or microglial caspase-3. Furthermore, butyrate, <em>A</em>. <em>muciniphila</em>, <em>R</em>. <em>faecis</em>, or <em>A</em>. <em>muciniphila</em> plus <em>R</em>. <em>faecis</em> restores KD-induced microglial caspase-3 activation and the anti-tumor phenotype of microglia in antibiotics-treated or germ-free mice. These findings highlight that targeting the gut microbiota by KD or supplementing with butyrate could be an effective strategy for glioma therapy.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"22 1","pages":""},"PeriodicalIF":44.5000,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Ketogenic diet inhibits glioma progression by promoting gut microbiota-derived butyrate production\",\"authors\":\"Ming-Liang Chen, Ying He, Xun-Hu Dong, Hao-Fei Liu, Ze-Xuan Yan, Xiao-Lu Lu, Qing-Qing Miao, Qing-Ning Zhao, Hang Zhang, Li Luo, Shuai Wang, Jing-Yuan Li, Dong-Fang Xiang, Yong Lin, Tian-Ran Li, Xin-Yue Zhou, Yang-Yang Zhou, Min Mao, Xia Zhang, Hong Wei, Xiu-Wu Bian\",\"doi\":\"10.1016/j.ccell.2025.09.002\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"The ketogenic diet (KD) is a potential therapeutic strategy for glioma; however, the underlying mechanisms remain unclear. Herein, we first identify that glioma patients exhibit a distinct gut microbial profile characterized by reduced butyrate-producing bacteria abundance, particularly <em>R</em>. <em>faecis</em>, along with decreased butyrate levels. Notably, KD reshapes the gut microbiota especially enriching <em>A</em>. <em>muciniphila</em> in a mucin-2-dependent manner, elevates butyrate production, and activates caspase-3 in microglia. These changes promote an anti-tumor microglial phenotype, ultimately suppressing glioma progression in mice. Crucially, KD’s anti-glioma effect is notably abolished by antibiotics treatment; germ-free condition; or specific depletion of mucin-2, microglia, or microglial caspase-3. Furthermore, butyrate, <em>A</em>. <em>muciniphila</em>, <em>R</em>. <em>faecis</em>, or <em>A</em>. <em>muciniphila</em> plus <em>R</em>. <em>faecis</em> restores KD-induced microglial caspase-3 activation and the anti-tumor phenotype of microglia in antibiotics-treated or germ-free mice. These findings highlight that targeting the gut microbiota by KD or supplementing with butyrate could be an effective strategy for glioma therapy.\",\"PeriodicalId\":9670,\"journal\":{\"name\":\"Cancer Cell\",\"volume\":\"22 1\",\"pages\":\"\"},\"PeriodicalIF\":44.5000,\"publicationDate\":\"2025-09-25\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cancer Cell\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.ccell.2025.09.002\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Cell","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.ccell.2025.09.002","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
Ketogenic diet inhibits glioma progression by promoting gut microbiota-derived butyrate production
The ketogenic diet (KD) is a potential therapeutic strategy for glioma; however, the underlying mechanisms remain unclear. Herein, we first identify that glioma patients exhibit a distinct gut microbial profile characterized by reduced butyrate-producing bacteria abundance, particularly R. faecis, along with decreased butyrate levels. Notably, KD reshapes the gut microbiota especially enriching A. muciniphila in a mucin-2-dependent manner, elevates butyrate production, and activates caspase-3 in microglia. These changes promote an anti-tumor microglial phenotype, ultimately suppressing glioma progression in mice. Crucially, KD’s anti-glioma effect is notably abolished by antibiotics treatment; germ-free condition; or specific depletion of mucin-2, microglia, or microglial caspase-3. Furthermore, butyrate, A. muciniphila, R. faecis, or A. muciniphila plus R. faecis restores KD-induced microglial caspase-3 activation and the anti-tumor phenotype of microglia in antibiotics-treated or germ-free mice. These findings highlight that targeting the gut microbiota by KD or supplementing with butyrate could be an effective strategy for glioma therapy.
期刊介绍:
Cancer Cell is a journal that focuses on promoting major advances in cancer research and oncology. The primary criteria for considering manuscripts are as follows:
Major advances: Manuscripts should provide significant advancements in answering important questions related to naturally occurring cancers.
Translational research: The journal welcomes translational research, which involves the application of basic scientific findings to human health and clinical practice.
Clinical investigations: Cancer Cell is interested in publishing clinical investigations that contribute to establishing new paradigms in the treatment, diagnosis, or prevention of cancers.
Insights into cancer biology: The journal values clinical investigations that provide important insights into cancer biology beyond what has been revealed by preclinical studies.
Mechanism-based proof-of-principle studies: Cancer Cell encourages the publication of mechanism-based proof-of-principle clinical studies, which demonstrate the feasibility of a specific therapeutic approach or diagnostic test.