Radford-Smith Daniel E, Oke Katharine, Costa Carolina F F A, Anthony Daniel C
Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, OX13QT, UK.
Brain Behav Immun Health. 2025 May 12;46:101013. doi: 10.1016/j.bbih.2025.101013. eCollection 2025 Jul.
Astrocytes are essential for preserving homeostasis, maintaining the blood-brain barrier, and they are a key element of the tripartite neuronal synapse. Despite such multifaceted roles, their importance as contributors to the microbiota-gut-brain axis studies, which typically focus on microglia and neurons, has been largely overlooked. This meta-analysis provides the first systematic review of the microbiota-gut-astrocyte (MGA) axis integrating findings across distinct neurological diseases.
A systematic narrative review was conducted per PRISMA guidelines. The search term employed for PubMed was and for Web of Science, Embase, and Scopus, with filters applied to exclude review articles. Searches were completed by May 9th 2024. Data extracted included study models, interventions, and outcomes related to astrocyte biology and rodent behaviour. SYRCLE's risk of bias tool was used to assess individual study designs.
53 studies met the inclusion criteria, covering rodent models of stroke and traumatic (acute) brain injury, chronic neurodegenerative diseases including Alzheimer's and Parkinson's disease and other heterogeneous models of cognitive impairment and affective disorders. Significant heterogeneity in methodology was observed between studies. Five studies had a high risk of bias, and 15 were low risk. Astrocyte biology, typically measured by GFAP expression, was increased in neurodegeneration and acute brain injury models but varied significantly in mood disorder models, depending on the source of stress. Common findings across diseases included altered gut microbiota, particularly an increased Bacteroidetes/Firmicutes ratio and compromised gut barrier integrity, linked to increased GFAP expression. Faecal microbiota transplants and microbial metabolite analyses suggested a direct impact of the gut microbiota on astrocyte biology and markers of neuroinflammation.
This review and meta-analysis describes the impact of the gut microbiota on astrocyte biology, and argues that the MGA axis is a promising therapeutic target for neurological disorders. However, it is clear that our understanding of the relationship between the gut microbiota and astrocyte behaviour is incomplete, including how different subtypes of astrocytes may be affected. Future studies must adopt new, multi-dimensional studies of astrocyte function and dysfunction, to elucidate their role in disease and explore the therapeutic potential of gut microbiota modulation.
星形胶质细胞对于维持体内平衡、保持血脑屏障至关重要，并且是三方神经元突触的关键要素。尽管具有如此多方面的作用，但它们作为微生物群-肠道-脑轴研究（该研究通常侧重于小胶质细胞和神经元）的贡献者的重要性在很大程度上被忽视了。这项荟萃分析首次对微生物群-肠道-星形胶质细胞（MGA）轴进行了系统综述，整合了不同神经疾病的研究结果。
按照PRISMA指南进行了系统的叙述性综述。在PubMed上使用的检索词为 ，在Web of Science、Embase和Scopus上使用的检索词为 ，并应用过滤器排除综述文章。检索于2024年5月9日完成。提取的数据包括与星形胶质细胞生物学和啮齿动物行为相关的研究模型、干预措施和结果。使用SYRCLE的偏倚风险工具评估单个研究设计。
53项研究符合纳入标准，涵盖中风和创伤性（急性）脑损伤的啮齿动物模型、包括阿尔茨海默病和帕金森病在内的慢性神经退行性疾病以及其他认知障碍和情感障碍的异质性模型。研究之间在方法上存在显著异质性。5项研究存在高偏倚风险，15项为低风险。星形胶质细胞生物学通常通过胶质纤维酸性蛋白（GFAP）表达来衡量，在神经退行性疾病和急性脑损伤模型中增加，但在情绪障碍模型中差异很大，这取决于应激源。不同疾病的共同发现包括肠道微生物群改变，特别是拟杆菌门/厚壁菌门比例增加以及肠道屏障完整性受损，这与GFAP表达增加有关。粪便微生物群移植和微生物代谢物分析表明肠道微生物群对星形胶质细胞生物学和神经炎症标志物有直接影响。
本综述和荟萃分析描述了肠道微生物群对星形胶质细胞生物学的影响，并认为MGA轴是神经疾病的一个有前景的治疗靶点。然而，很明显我们对肠道微生物群与星形胶质细胞行为之间关系的理解并不完整，包括不同亚型的星形胶质细胞可能如何受到影响。未来的研究必须采用新的、多维度的星形胶质细胞功能和功能障碍研究，以阐明它们在疾病中的作用，并探索调节肠道微生物群的治疗潜力。
