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.

中文翻译：

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肠脑轴芯片中肠道微生物群衍生的代谢物和细胞外囊泡对神经退行性疾病的影响

一种新的观点表明，肠道、微生物组和中枢神经系统 (CNS) 之间存在一个动态的双向通讯系统，通常被称为微生物组-肠-脑轴。该系统可能会影响大脑健康和各种与大脑相关的疾病，特别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有能力穿过肠上皮屏障或血脑屏障，进入体循环。这种现象可以引发直接或间接影响中枢神经系统及其功能的生理反应。然而，需要可靠且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影响。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，我们利用肠脑轴芯片中的人类诱导多能干细胞 (iPSC) 衍生的神经元，研究了微生物衍生的代谢物和外泌体对神经发育和神经退行性疾病的影响。虽然具有菌株特异性，但我们的研究结果表明微生物衍生的代谢物和外泌体对神经生长、成熟和突触可塑性产生显着影响。因此，我们的结果表明，源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。