Combination of Sodium Butyrate and Immunotherapy in Glioma: regulation of immunologically hot and cold tumors via gut microbiota and metabolites

作者：Li Sui, Li Wang, Mingyu Han, Huali Fan, Hailin Tang, Huile Gao, Guo‐Bo Li, Zheng Xu, Zhaokai Zhou, Junrong Du, Cheng Peng, Peng Fu · 发表于：Frontiers in Immunology · 年份：2025 · DOI：10.3389/fimmu.2025.1532528 · 被引用次数：17 · 研究领域：Gut microbiota and health、Immune cells in cancer、Cancer Research and Treatments

Background Recent studies have highlighted the importance of cross-talk along the gut-brain axis in regulating inflammatory nociception, inflammatory responses, and immune homeostasis. The gut microbiota, particularly its bacterial composition, plays a crucial role in the development and function of the immune system. Moreover, metabolites produced by the gut microbiota can significantly impact both systemic immune responses and central nervous system (CNS) immunity. Sodium butyrate is a key metabolite produced by the gut microbiota and, as a histone deacetylase inhibitor, can enhance the anti-tumor immunity of cytotoxic CD8 + T cells. However, it remains unclear whether sodium butyrate treatment can enhance the efficacy of PD-1 blockade in glioma therapy. In this research, the effect and underlying mechanism of combination of gut microbiota metabolites and anti-mouse PD-1 mAb on glioma has been investigated. Methods RNA-seq assay in glioma cell and biomedical databases, including ONCOMINE, GEPIA and TCGA were incorporated. Subsequently, the inhibitory effect of sodium butyrate on glioma cells and its related mechanisms were assessed through Counting Kit-8 (CCK-8), Flow Cytometry, Western blot (WB), reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and other in vitro experiments. In vitro , an orthotopic mouse glioma model was established. MRI imaging, Immunohistochemistry, and Immune cell flow cytometry were used to investigate the therapeutic effects o...