Wang Yi-Hsin, Liao Jiuan-Miaw, Jan Ming-Shiou, Wang Meilin, Su Hsing-Hui, Tsai Wan-Hua, Liu Pei-Hsun, Tsuei Yuang-Seng, Huang Shiang-Suo
Department of Physiology, Chung Shan Medical University, Taichung, Taiwan; Department of Medical Education, Chung Shan Medical University Hospital, Taichung, Taiwan.
Department of Health Industry Technology Management, Chung Shan Medical University, Taichung, Taiwan.
Brain Behav Immun. 2025 Jan;123:784-798. doi: 10.1016/j.bbi.2024.10.026. Epub 2024 Oct 22.
A growing body of research has focused on the role of spleen in orchestrating brain injury through the peripheral immune system following stroke, highlighting the brain-spleen axis as a potential target for mitigating neuronal damage during stroke. The gut microbiota plays a pivotal role in the bidirectional communication between the gut and the brain. Several studies have suggested that probiotic supplements hold promise as a strategic approach to maintaining a balanced intestinal microecology, reducing the apoptosis of intestinal epithelial cells, protecting the intestinal mucosal and blood-brain barrier (BBB), enhancing both intestinal and systemic immune functions, and thereby potentially affecting the pathogenesis and progression of ischemic stroke. In this study, we aimed to clarify the neuroprotective effects of supplementation with Lactobacillus, specifically Limosilactobacillus reuteri GMNL-89 (G89) and Lacticaseibacillus paracasei GMNL-133 (G133) on ischemic stroke and investigate how G89 and G133 modulate the communication mechanisms between the gut, brain, and spleen following ischemic stroke. We explored the neuroprotection and the underlying mechanisms of Lactobacillus supplementation in C57BL/6 mice subjected to permanent middle cerebral artery occlusion. Our results revealed that oral treatment with G89 or G133 alone, as well as oral administration combining G89 and G133, significantly decreased the infarct volume and improved the neurological function in mice with ischemic stroke. Moreover, G89 treatment alone preserved the tight junction integrity of gut barrier, while G133 alone and the combined treatment of G89 and G133 would significantly decreased the BBB permeability, and thereby significantly attenuated stroke-induced local and systemic inflammatory responses. Both G89 and G133 regulated cytotoxic T cells, and the balance between T helper 1 cells and T helper 2 cells in the spleen following ischemic stroke. Additionally, the combined administration of G89 and G133 improved the gut dysbiosis and significantly increased the concentration of short-chain fatty acids. In conclusion, our findings suggest that G89 and G133 may be used as nutrient supplements, holding promise as a prospective approach to combat ischemic stroke by modulating the gut-spleen-brain axis.
越来越多的研究聚焦于脾脏在中风后通过外周免疫系统协调脑损伤中的作用，凸显了脑-脾轴作为减轻中风期间神经元损伤的潜在靶点。肠道微生物群在肠道与大脑的双向通信中起关键作用。多项研究表明，补充益生菌有望作为维持肠道微生态平衡、减少肠道上皮细胞凋亡、保护肠道黏膜和血脑屏障（BBB）、增强肠道和全身免疫功能、从而可能影响缺血性中风发病机制和进展的一种策略。在本研究中，我们旨在阐明补充乳酸杆菌，特别是罗伊氏乳杆菌GMNL-89（G89）和副干酪乳杆菌GMNL-133（G133）对缺血性中风的神经保护作用，并研究G89和G133如何调节缺血性中风后肠道、大脑和脾脏之间的通信机制。我们探讨了补充乳酸杆菌对永久性大脑中动脉闭塞的C57BL/6小鼠的神经保护作用及潜在机制。我们的结果显示，单独口服G89或G133，以及联合口服G89和G133，均可显著减少缺血性中风小鼠的梗死体积并改善神经功能。此外，单独使用G89治疗可维持肠道屏障的紧密连接完整性，而单独使用G133以及G89和G133联合治疗可显著降低血脑屏障通透性，从而显著减轻中风诱导的局部和全身炎症反应。G89和G133均可调节缺血性中风后脾脏中细胞毒性T细胞以及辅助性T细胞1和辅助性T细胞2之间的平衡。此外，G89和G133联合给药可改善肠道菌群失调并显著提高短链脂肪酸浓度。总之，我们的研究结果表明，G89和G133可用作营养补充剂，有望作为一种通过调节肠-脾-脑轴来对抗缺血性中风的前瞻性方法。
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