Prophylactic use of probiotics as an adjunctive treatment for ischemic stroke via the gut-spleen-brain axis

IF 8.8 2区 医学 Q1 IMMUNOLOGY Brain, Behavior, and Immunity Pub Date : 2024-10-22 DOI:10.1016/j.bbi.2024.10.026
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Abstract

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.
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通过肠道-脾脏-大脑轴预防性使用益生菌作为缺血性中风的辅助治疗。
越来越多的研究关注中风后脾脏通过外周免疫系统协调脑损伤的作用,强调脑-脾轴是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之间的双向交流中发挥着关键作用。多项研究表明,益生菌补充剂有望成为维持肠道微生态平衡的战略方法,减少肠道上皮细胞凋亡,保护肠道粘膜和血脑屏障(BBB),增强肠道和全身免疫功能,从而可能影响缺血性脑卒中的发病机制和进展。本研究旨在阐明补充乳酸杆菌,特别是Limosilactobacillus reuteri GMNL-89(G89)和Lacticaseibacillus paracasei GMNL-133(G133)对缺血性脑卒中的神经保护作用,并研究G89和G133如何调节缺血性脑卒中后肠道、大脑和脾脏之间的沟通机制。我们对C57BL/6小鼠永久性大脑中动脉闭塞后补充乳酸菌的神经保护作用及其内在机制进行了探讨。我们的研究结果表明,单独口服 G89 或 G133 以及同时口服 G89 和 G133 能显著减少缺血性脑卒中小鼠的梗死体积并改善其神经功能。此外,G89单独治疗可保持肠道屏障紧密连接的完整性,而G133单独治疗以及G89和G133联合治疗可显著降低BBB的通透性,从而显著减轻中风引起的局部和全身炎症反应。G89和G133都能调节缺血性中风后脾脏中的细胞毒性T细胞以及T辅助1细胞和T辅助2细胞之间的平衡。此外,联合服用 G89 和 G133 还能改善肠道菌群失调,并显著提高短链脂肪酸的浓度。总之,我们的研究结果表明,G89 和 G133 可用作营养补充剂,有望成为通过调节肠道-脾脏-大脑轴来防治缺血性中风的一种前瞻性方法。
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来源期刊
CiteScore
29.60
自引率
2.00%
发文量
290
审稿时长
28 days
期刊介绍: Established in 1987, Brain, Behavior, and Immunity proudly serves as the official journal of the Psychoneuroimmunology Research Society (PNIRS). This pioneering journal is dedicated to publishing peer-reviewed basic, experimental, and clinical studies that explore the intricate interactions among behavioral, neural, endocrine, and immune systems in both humans and animals. As an international and interdisciplinary platform, Brain, Behavior, and Immunity focuses on original research spanning neuroscience, immunology, integrative physiology, behavioral biology, psychiatry, psychology, and clinical medicine. The journal is inclusive of research conducted at various levels, including molecular, cellular, social, and whole organism perspectives. With a commitment to efficiency, the journal facilitates online submission and review, ensuring timely publication of experimental results. Manuscripts typically undergo peer review and are returned to authors within 30 days of submission. It's worth noting that Brain, Behavior, and Immunity, published eight times a year, does not impose submission fees or page charges, fostering an open and accessible platform for scientific discourse.
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