Ketogenic diet inhibits glioma progression by promoting gut microbiota-derived butyrate production
Menée à l'aide de xénogreffes sur des modèles murins et à l'aide d'échantillons fécaux prélevés sur des témoins en bonne santé et des patients atteints d'un glioblastome, cette étude met en évidence un mécanisme par lequel un régime cétogène inhibe la progression des gliomes en favorisant la production de butyrate par le microbiote intestinal
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.
Cancer Cell , résumé, 2025