Short-Chain Fatty Acids Improve Poststroke Recovery via Immunological Mechanisms
Short-Chain Fatty Acids Improve Poststroke Recovery via Immunological Mechanisms
复制标题
短链脂肪酸通过免疫机制促进中风后恢复
DOI：
10.1523/jneurosci.1359-19.2019
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发表时间：
2020-01-29
影响因子：
5.3
通讯作者：
Liesz, Arthur
中科院分区：
文献类型：
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作者：
Sadler, Rebecca;Cramer, Julia V.;Liesz, Arthur
中风后的恢复是一个多细胞过程，包括神经元、常驻免疫细胞和脑侵袭细胞。中风会改变肠道微生物群，进而对中风结果产生相当大的影响。然而，肠-脑相互作用的机制及其对长期恢复的影响在很大程度上是难以捉摸的。在这里，我们测试了这样的假设：短链脂肪酸（SCFA）是关键的生物活性微生物代谢物，是肠脑轴上缺失的一环，并且可能能够调节实验性中风后的恢复。在雄性小鼠的饮用水中添加 SCFA 显着改善了受影响肢体运动功能的恢复。使用体内广域钙成像，我们观察到 SCFA 诱导改变对侧皮层连接。这与 SCFA 依赖性的脊柱和突触密度变化有关。前脑皮层的 RNA 测序表明小胶质细胞可能参与结构和功能重塑。进一步的分析证实了 SCFA 对小胶质细胞激活的重大影响，这取决于梗塞大脑中 T 细胞的募集。我们的研究结果表明，微生物群衍生的 SCFA 通过影响全身和大脑常驻免疫细胞来调节中风后恢复。
Recovery after stroke is a multicellular process encompassing neurons, resident immune cells, and brain-invading cells. Stroke alters the gut microbiome, which in turn has considerable impact on stroke outcome. However, the mechanisms underlying gut-brain interaction and implications for long-term recovery are largely elusive. Here, we tested the hypothesis that short-chain fatty acids (SCFAs), key bioactive microbial metabolites, are the missing link along the gut- brain axis and might be able to modulate recovery after experimental stroke. SCFA supplementation in the drinking water of male mice significantly improved recovery of affected limb motor function. Using in vivo wide-field calcium imaging, we observed that SCFAs induced altered contralesional cortex connectivity. This was associated with SCFA-dependent changes in spine and synapse densities. RNA sequencing of the forebrain cortex indicated a potential involvement of microglial cells in contributing to the structural and functional remodeling. Further analyses confirmed a substantial impact of SCFAs on microglial activation, which depended on the recruitment of T cells to the infarcted brain. Our findings identified that microbiota-derived SCFAs modulate poststroke recovery via effects on systemic and brain resident immune cells.