ML. Chen, Y. He, XH. Dong, HF. Liu, ZX. Yan, XL. Lu, QQ. Miao, QN. Zhao, H. Zhang, L. Luo, S. Wang, JY. Li, DF. Xiang, Y. Lin, TR. Li, XY. Zhou, YY. Zhou, M. Mao, X. Zhang, H. Wei, Y. Shi, XD. Liu, YF. Ping, et al. (2025). Ketogenic diet inhibits glioma progression by promoting gut microbiota-derived butyrate production. Cancer cell, 43(11), 2119-2135.e10. https://doi.org/10.1016/j.ccell.2025.09.002

PubMed 41005305

[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 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.