Kim Chae Won, Kim Hyun-Jin, Kang In, Ku Keun Bon, Kim Yumin, Park Jang Hyun, Lim Juhee, Kang Byeong Hoon, Park Won Hyung, La Jeongwoo, Chang Sungwoo, Hwang Inju, Kim Minji, Ahn Stephen, Lee Heung Kyu
Laboratory of Host Defenses, Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea.
KAIST Life Science Institute, KAIST , Daejeon, Republic of Korea.
J Exp Med. 2025 Aug 4;222(8). doi: 10.1084/jem.20241135. Epub 2025 May 22.
The purpose of this study is to investigate the impact of a high-salt diet (HSD), which is commonly found in Western countries, on the progression of glioma. Our research shows that the alterations in gut microbiota caused by an HSD facilitated the development of glioma. Mice fed an HSD have elevated levels of intestinal propionate, which accelerated the growth of glioma cells. We also find that propionate supplementation enhanced the response of glioma cells to low oxygen levels. Moreover, we identify a link between TGF-β signaling, response to low oxygen levels, and invasion-related pathways. Propionate treatment increases the expression of HIF-1α, leading to an increase in TGF-β1 production. Additionally, propionate treatment promotes glioma cell invasion through TGF-β signaling. Our findings suggest that an HSD-induced increase in propionate plays a crucial role in glioma progression by facilitating invasion through the hypoxic response and TGF-β signaling pathways, thereby establishing a significant connection between gut microbiota and the progression of glioma.
本研究的目的是调查在西方国家常见的高盐饮食（HSD）对神经胶质瘤进展的影响。我们的研究表明，高盐饮食引起的肠道微生物群改变促进了神经胶质瘤的发展。喂食高盐饮食的小鼠肠道丙酸水平升高，这加速了神经胶质瘤细胞的生长。我们还发现，补充丙酸增强了神经胶质瘤细胞对低氧水平的反应。此外，我们确定了转化生长因子-β（TGF-β）信号传导、对低氧水平的反应和侵袭相关途径之间的联系。丙酸处理增加了缺氧诱导因子-1α（HIF-1α）的表达，导致转化生长因子-β1（TGF-β1）产生增加。此外，丙酸处理通过TGF-β信号传导促进神经胶质瘤细胞侵袭。我们的研究结果表明，高盐饮食诱导的丙酸增加通过促进缺氧反应和TGF-β信号通路的侵袭在神经胶质瘤进展中起关键作用，从而在肠道微生物群与神经胶质瘤进展之间建立了重要联系。
