Recent developments in microbiome research suggest that the gut microbiome may remotely modulate central and peripheral neuronal processes, ranging from early brain development to age-related changes. Dysbiotic microbiome configurations have been increasingly associated with neurological disorders, such as neurodegeneration, but causal understanding of these associations remains limited. Most mechanisms explaining how the microbiome may induce such remote neuronal effects involve microbially modulated metabolites that influx into the ‘sterile’ host. Some metabolites are able to cross the blood-brain barrier (BBB) to reach the central nervous system, where they can impact a variety of cells and processes. Alternatively, metabolites may directly signal to peripheral nerves to act as neurotransmitters or exert modulatory functions, or impact immune responses, which, in turn, modulate neuronal function and associated disease propensity. Herein, we review the current knowledge highlighting microbiome-modulated metabolite impacts on neuronal disease, while discussing unknowns, controversies and prospects impacting this rapidly evolving research field.

中文翻译：

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微生物组衍生代谢物对神经退行性疾病产生影响的机制


微生物组研究的最新进展表明，肠道微生物组可能远程调节中枢和周围神经元过程，范围从早期大脑发育到与年龄相关的变化。失调的微生物组结构与神经系统疾病（例如神经退行性变）的关系越来越密切，但对这些关联的因果关系的理解仍然有限。大多数解释微生物组如何诱导这种远程神经元效应的机制都涉及流入“无菌”宿主的微生物调节代谢物。一些代谢物能够穿过血脑屏障 (BBB) 到达中枢神经系统，在那里它们可以影响各种细胞和过程。或者，代谢物可以直接向周围神经发出信号，充当神经递质或发挥调节功能，或影响免疫反应，从而调节神经元功能和相关疾病倾向。在此，我们回顾了当前的知识，重点介绍了微生物组调节的代谢物对神经元疾病的影响，同时讨论了影响这一快速发展的研究领域的未知因素、争议和前景。