Division of Biology & Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA.
Nat Rev Neurosci. 2020 Dec;21(12):717-731. doi: 10.1038/s41583-020-00381-0. Epub 2020 Oct 16.
Mounting evidence suggests that the gut microbiome impacts brain development and function. Gut-brain connections may be mediated by an assortment of microbial molecules that are produced in the gastrointestinal tract, which can subsequently permeate many organs, including sometimes the brain. Studies in animal models have identified molecular cues propagated from intestinal bacteria to the brain that can affect neurological function and/or neurodevelopmental and neurodegenerative conditions. Herein, we describe bacterial metabolites with known or suspected neuromodulatory activity, define mechanisms of signalling pathways from the gut microbiota to the brain and discuss direct effects that gut bacterial molecules are likely exerting on specific brain cells. Many discoveries are recent, and the findings described in this Perspective are largely novel and yet to be extensively validated. However, expanding research into the dynamic molecular communications between gut microorganisms and the CNS continues to uncover critical and previously unappreciated clues in understanding the pathophysiology of behavioural, psychiatric and neurodegenerative diseases.
越来越多的证据表明，肠道微生物群会影响大脑的发育和功能。肠道-大脑的连接可能是由一系列在胃肠道中产生的微生物分子介导的，这些分子随后可以渗透到许多器官，包括有时大脑。动物模型研究已经确定了从肠道细菌传播到大脑的分子线索，这些线索可以影响神经功能和/或神经发育和神经退行性疾病。在此，我们描述了具有已知或疑似神经调节活性的细菌代谢产物，定义了肠道微生物群到大脑的信号通路的机制，并讨论了肠道细菌分子可能对特定脑细胞施加的直接影响。许多发现都是最近的，本观点中描述的发现很大程度上是新颖的，尚待广泛验证。然而，对肠道微生物和中枢神经系统之间动态分子通讯的扩展研究不断揭示出理解行为、精神和神经退行性疾病的病理生理学的关键且以前未被重视的线索。
