胶质母细胞瘤（GBM）被称为中枢神经系统最恶性和最常见的原发性脑肿瘤，治疗选择有限且预后不良。研究表明，宿主肠道微生物以多种不同的方式直接或间接地在胃肠外肿瘤的免疫调节中发挥作用。然而，肠道微生物群对肿瘤微环境，特别是神经胶质瘤免疫环境的潜在影响尚未明确。在这项研究中，通过使用原位 GBM 模型，我们发现抗生素鸡尾酒治疗引起的肠道微生物群失调促进了体内肿瘤的进展。肠道菌群失调后的一个明显变化是 TME 中 M2 样巨噬细胞的百分比增加，同时肠道微生物代谢物、血液和肿瘤组织中的短链脂肪酸 (SCFA) 水平下降。口服补充 SCFA 可以增加 TME 中 M1 样巨噬细胞的比例，从而改善神经胶质瘤的治疗结果。就机制而言，SCFAs 激活肿瘤相关巨噬细胞中的糖酵解可能是 TME 中 M1 极化升高的原因。这项研究将使我们更好地理解“肠-脑”轴，对于针对 GBM 患者开发 TAM 靶向免疫治疗策略具有重要意义。版权所有 © 2024。由 Elsevier B.V. 出版。

Glioblastoma (GBM), known as the most malignant and common primary brain tumor of the central nervous system, has finite therapeutic options and a poor prognosis. Studies have shown that host intestinal microorganisms play a role in the immune regulation of parenteral tumors in a number of different ways, either directly or indirectly. However, the potential impact of gut microbiota on tumor microenvironment, particularly glioma immunological milieu, has not been clarified exactly. In this study, by using an orthotopic GBM model, we found gut microbiota dysbiosis caused by antibiotic cocktail treatment boosted the tumor process in vivo. An obvious change that followed gut microbiota dysbiosis was the enhanced percentage of M2-like macrophages in the TME, in parallel with a decrease in the levels of gut microbial metabolite, short-chain fatty acids (SCFAs) in the blood and tumor tissues. Oral supplementation with SCFAs can increase the proportion of M1-like macrophages in the TME, which improves the outcomes of glioma. In terms of mechanism, SCFAs-activated glycolysis in the tumor-associated macrophages may be responsible for the elevated M1 polarization in the TME. This study will enable us to better comprehend the "gut-brain" axis and be meaningful for the development of TAM-targeting immunotherapeutic strategies for GBM patients.Copyright © 2024. Published by Elsevier B.V.