Ma Brian D Y, Chan Travis Y H, Lo Benjamin W Y
Department of Neurosurgery, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong.
Department of Neurosurgery, Queen Mary Hospital, Pok Fu Lam, Hong Kong Hospital Authority, Hong Kong.
Surg Neurol Int. 2024 Nov 1;15:394. doi: 10.25259/SNI_703_2024. eCollection 2024.
The brain-gut axis represents a bidirectional communication network between the gut microbiome and the central nervous system that plays an important role in homeostasis. Compelling evidence now confirms that ischemic stroke disrupts this delicate balance by inducing gut dysbiosis.
A comprehensive literature search was performed in PubMed, Web of Science, and Google Scholar for articles published between January 2000 and January 2023 using relevant keywords. Studies were limited to English and included original studies, literature, and systematic reviewers from peer-reviewed journals which discussed gut microbiota composition in models/subjects with ischemic stroke or assessed stroke impact on gut microbiota. Comments, meeting abstracts, and case reports were excluded. From the 80 relevant articles, we summarized key findings related to gut microbiota changes after stroke and their association with stroke outcomes.
Emerging preclinical evidence underscores the pivotal role of the gut microbiome in glial cell development and function. Germ-free models exhibit compromised microglial activation and impaired cellular debris clearance, exacerbating tissue damage following ischemic stroke. Targeted interventions, including prebiotics, probiotics, and fecal microbiota transplantation, have demonstrated efficacy in rescuing glial phenotypes in preclinical stroke models. Beyond its local effects, the gut microbiome significantly influences systemic immunity. Ischemic stroke polarizes pro-inflammatory phenotypes of neutrophils and T cells, amplifying neurovascular inflammation. Microbiota manipulation modulates leukocyte trafficking and metabolic signaling, offering potential avenues to mitigate infarct pathology.
Our review demonstrates that in preclinical stroke models, modulating the lipopolysaccharide, short-chain fatty acid, and trimethylamine N-oxide pathways through the gut-brain axis reduces infarct sizes and edema and improves functional recovery after ischemic stroke. Further exploration of this important axis may unveil additional adjunctive stroke therapies by elucidating the complex interplay between the microbiome and the brain. Rigorously controlled clinical studies are now warranted to translate these promising preclinical findings and investigate whether manipulating the microbiome-brain relationship can help improve outcomes for stroke patients. Overall, continued research on the gut-brain axis holds exciting possibilities for developing novel treatment strategies that may enhance recovery after stroke.
脑-肠轴代表肠道微生物群与中枢神经系统之间的双向通信网络，在体内平衡中起重要作用。目前有确凿证据证实，缺血性中风通过诱导肠道菌群失调破坏了这种微妙的平衡。
在PubMed、科学网和谷歌学术上进行了全面的文献检索，使用相关关键词查找2000年1月至2023年1月发表的文章。研究限于英文，包括原始研究、文献以及来自同行评审期刊的系统评价，这些研究讨论了缺血性中风模型/受试者中的肠道微生物群组成或评估了中风对肠道微生物群的影响。评论、会议摘要和病例报告被排除。从80篇相关文章中，我们总结了中风后肠道微生物群变化的关键发现及其与中风结局的关联。
新出现的临床前证据强调了肠道微生物群在胶质细胞发育和功能中的关键作用。无菌模型显示小胶质细胞激活受损和细胞碎片清除受损，加剧了缺血性中风后的组织损伤。包括益生元、益生菌和粪便微生物群移植在内的靶向干预措施已在临床前中风模型中证明对挽救胶质细胞表型有效。除了其局部作用外，肠道微生物群还显著影响全身免疫。缺血性中风使中性粒细胞和T细胞的促炎表型极化，放大神经血管炎症。微生物群操纵调节白细胞运输和代谢信号，为减轻梗死病理提供了潜在途径。
我们的综述表明，在临床前中风模型中，通过脑-肠轴调节脂多糖、短链脂肪酸和氧化三甲胺途径可减少梗死面积和水肿，并改善缺血性中风后的功能恢复。对这一重要轴的进一步探索可能通过阐明微生物群与大脑之间的复杂相互作用揭示更多辅助性中风治疗方法。现在需要进行严格控制的临床研究，以转化这些有前景的临床前发现，并研究操纵微生物群-脑关系是否有助于改善中风患者的结局。总体而言，对脑-肠轴的持续研究为开发可能增强中风后恢复的新型治疗策略带来了令人兴奋的可能性。
