PDF(Pubmed)
Abstract：
A new perspective suggests that a dynamic bidirectional communication system, often referred to as the microbiome-gut-brain axis, exists among the gut, its microbiome, and the central nervous system (CNS). This system may influence brain health and various brain-related diseases, especially in the realms of neurodevelopmental and neurodegenerative conditions. However, the exact mechanism is not yet understood. Metabolites or extracellular vesicles derived from microbes in the gut have the capacity to traverse the intestinal epithelial barrier or blood-brain barrier, gaining access to the systemic circulation. This phenomenon can initiate the physiological responses that directly or indirectly impact the CNS and its function. However, reliable and controllable tools are required to demonstrate the causal effects of gut microbial-derived substances on neurogenesis and neurodegenerative diseases. The integration of microfluidics enhances scientific research by providing advanced in vitro engineering models. In this study, we investigated the impact of microbe-derived metabolites and exosomes on neurodevelopment and neurodegenerative disorders using human induced pluripotent stem cells (iPSCs)-derived neurons in a gut-brain axis chip. While strain-specific, our findings indicate that both microbial-derived metabolites and exosomes exert the significant effects on neural growth, maturation, and synaptic plasticity. Therefore, our results suggest that metabolites and exosomes derived from microbes hold promise as potential candidates and strategies for addressing neurodevelopmental and neurodegenerative disorders.
摘要：
一个新的观点表明，一个动态的双向通信系统，通常被称为微生物组-肠-脑轴，存在于肠道中，它的微生物组，和中枢神经系统（CNS）。这个系统可能会影响大脑健康和各种与大脑相关的疾病，尤其是在神经发育和神经退行性疾病领域。然而,确切的机制尚不清楚。来自肠道微生物的代谢物或细胞外囊泡具有穿越肠上皮屏障或血脑屏障的能力，进入全身循环。这种现象可以引发直接或间接影响CNS及其功能的生理反应。然而,需要可靠和可控的工具来证明肠道微生物衍生物质对神经发生和神经退行性疾病的因果关系。微流体的集成通过提供先进的体外工程模型来增强科学研究。在这项研究中,我们在肠-脑轴芯片中使用人诱导多能干细胞(iPSCs)来源的神经元,研究了微生物来源的代谢物和外泌体对神经发育和神经退行性疾病的影响.虽然菌株特异性，我们的发现表明，微生物来源的代谢物和外泌体对神经生长都有显著的影响，成熟,和突触可塑性。因此,我们的研究结果表明,来自微生物的代谢物和外泌体有望成为解决神经发育和神经退行性疾病的潜在候选者和策略.
