Sorbonne Université, Inserm, Centre de Recherche Saint-Antoine, CRSA, Immune System and Neuroinflammation Laboratory, Hôpital Saint-Antoine, F-75012, Paris, France.
Department of Physiology, Nanjing Medical University, Nanjing, 211166, China.
Mol Neurodegener. 2022 Mar 5;17(1):19. doi: 10.1186/s13024-022-00522-2.
The implication of gut microbiota in the control of brain functions in health and disease is a novel, currently emerging concept. Accumulating data suggest that the gut microbiota exert its action at least in part by modulating neuroinflammation. Given the link between neuroinflammatory changes and neuronal activity, it is plausible that gut microbiota may affect neuronal functions indirectly by impacting microglia, a key player in neuroinflammation. Indeed, increasing evidence suggests that interplay between microglia and synaptic dysfunction may involve microbiota, among other factors. In addition to these indirect microglia-dependent actions of microbiota on neuronal activity, it has been recently recognized that microbiota could also affect neuronal activity directly by stimulation of the vagus nerve.
The putative mechanisms of the indirect and direct impact of microbiota on neuronal activity are discussed by focusing on Alzheimer's disease, one of the most studied neurodegenerative disorders and the prime cause of dementia worldwide. More specifically, the mechanisms of microbiota-mediated microglial alterations are discussed in the context of the peripheral and central inflammation cross-talk. Next, we highlight the role of microbiota in the regulation of humoral mediators of peripheral immunity and their impact on vagus nerve stimulation. Finally, we address whether and how microbiota perturbations could affect synaptic neurotransmission and downstream cognitive dysfunction.
There is strong increasing evidence supporting a role for the gut microbiome in the pathogenesis of Alzheimer's disease, including effects on synaptic dysfunction and neuroinflammation, which contribute to cognitive decline. Putative early intervention strategies based on microbiota modulation appear therapeutically promising for Alzheimer's disease but still require further investigation.
肠道微生物群在健康和疾病中控制大脑功能的作用是一个新颖的、当前正在出现的概念。越来越多的证据表明，肠道微生物群至少通过调节神经炎症来发挥其作用。鉴于神经炎症变化和神经元活动之间的联系，肠道微生物群可以通过影响小胶质细胞（神经炎症的关键参与者）间接影响神经元功能，这是合理的。事实上，越来越多的证据表明，小胶质细胞和突触功能障碍之间的相互作用可能涉及微生物群等因素。除了微生物群对神经元活动的这些间接的、依赖小胶质细胞的作用外，人们最近还认识到，微生物群还可以通过刺激迷走神经直接影响神经元活动。
通过关注阿尔茨海默病（一种研究最多的神经退行性疾病，也是全球痴呆症的主要原因），讨论了微生物群对神经元活动的间接和直接影响的推测机制。更具体地说，在探讨外周和中枢炎症串扰时，讨论了微生物群介导的小胶质细胞改变的机制。接下来，我们强调了微生物群在调节外周免疫体液介质及其对迷走神经刺激的影响中的作用。最后，我们探讨了微生物群的扰动是否以及如何影响突触神经传递和下游认知功能障碍。
越来越多的证据支持肠道微生物组在阿尔茨海默病发病机制中的作用，包括对突触功能障碍和神经炎症的影响，这些影响导致认知能力下降。基于微生物群调节的推测早期干预策略似乎对阿尔茨海默病具有治疗前景，但仍需要进一步研究。
