肠道微生物群诱导胶质母细胞瘤中基因表达、RNA甲基化和代谢的免疫相关改变，这些改变由单细胞和空间多组学揭示
Gut microbiota induces immune-related alterations in gene expression, RNA methylation, and metabolism in glioblastoma revealed by single-cell and spatial multi-omics.
摘要(中文译文)
胶质母细胞瘤（GBM）是一种高度恶性的肿瘤，预后差且有效治疗选择有限。新兴研究表明，肠道微生物群可能通过肠-脑轴影响胶质瘤的进展，但其确切机制在很大程度上仍不清楚。在本研究中，我们采用综合多组学方法——涵盖单细胞转录组学、空间转录组学、宏基因组学、代谢组学和m6A测序——以研究抗生素诱导的肠道微生物群破坏如何影响小鼠模型中的胶质瘤进展。基因表达分析显示，抗生素处理小鼠（ABX处理小鼠）中存在显著改变，包括Epha6表达降低和Tead1表达上调，这些是与胶质瘤进展和免疫调节相关的关键基因。空间转录组学和代谢组学分析发现，ABX处理小鼠胶质瘤中甲硫氨酸水平降低，将肠道来源的代谢物变化与通过m6A甲基化介导的表观遗传调控联系起来。单细胞RNA测序进一步证明AC样细胞比例增加、细胞间通讯受到破坏以及EPHA和NRXN信号通路异常。这些发现突出了肠道微生物群、免疫信号和表观遗传修饰在塑造胶质瘤微环境中的相互作用。本研究推进了我们对胶质瘤生物学中肠-脑轴的理解，并提出EPHA通路作为免疫介导的肿瘤进展调节的有前景的生物标志物，从而为肠-脑轴在胶质瘤调控中的作用提供了新的见解。
Abstract
Glioblastoma (GBM) is a highly malignant tumor with poor prognosis and limited effective treatment options. Emerging studies have suggested that gut microbiota may influence glioma progression through the gut-brain axis, though the precise mechanisms remain largely unclear. In this study, we employed a comprehensive multi-omics approach-encompassing single-cell transcriptomics, spatial transcriptomics, metagenomics, metabolomics, and m6A-seq-to investigate how antibiotic-induced gut microbiota disruption impacts glioma progression in a mouse model. Gene expression analysis revealed significant alterations in antibiotics-treated mice (ABX-treated mice), including reduced expression of Epha6 and upregulated expression of Tead1, key genes associated with glioma progression and immune modulation. Spatial transcriptomics and metabolomic profiling identified reduced methionine levels in gliomas of ABX-treated mice, linking gut-derived metabolite changes to epigenetic regulation via m6A methylation. Single-cell RNA sequencing further demonstrated an increased proportion of AC-like cells, disrupted intercellular communication, and aberrations in the EPHA and NRXN signaling pathways. These findings highlight the interplay between gut microbiota, immune signaling, and epigenetic modifications in shaping the glioma microenvironment. This study advances our understanding of the gut-brain axis in glioma biology and proposes the EPHA pathway as a promising biomarker for the immune-mediated modulation of tumor progression, thereby providing new insights into the role of the gut-brain axis in glioma regulation.
如何引用
AMA
Mingcong Chen, Xiang Wang, Gang Peng, Lihe Jiang, Hao Liang, Ping Cui. Gut microbiota induces immune-related alterations in gene expression, RNA methylation, and metabolism in glioblastoma revealed by single-cell and spatial multi-omics.. Frontiers in immunology. 2026; doi:10.3389/fimmu.2026.1899954.
APA
Mingcong Chen, Xiang Wang, Gang Peng, Lihe Jiang, Hao Liang, Ping Cui (2026). Gut microbiota induces immune-related alterations in gene expression, RNA methylation, and metabolism in glioblastoma revealed by single-cell and spatial multi-omics.. Frontiers in immunology. https://doi.org/10.3389/fimmu.2026.1899954
GB/T 7714
Mingcong Chen, Xiang Wang, Gang Peng, Lihe Jiang, Hao Liang, Ping Cui. Gut microbiota induces immune-related alterations in gene expression, RNA methylation, and metabolism in glioblastoma revealed by single-cell and spatial multi-omics.[J]. Frontiers in immunology, 2026 doi:10.3389/fimmu.2026.1899954.
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