Department of Environmental and Occupational Health Sciences, University of Washington, United States.
Department of Environmental and Occupational Health Sciences, University of Washington, United States.
Neurotoxicology. 2019 Dec;75:41-69. doi: 10.1016/j.neuro.2019.08.005. Epub 2019 Aug 24.
There is growing recognition that the gut microbiome is an important regulator for neurological functions. This review provides a summary on the role of gut microbiota in various neurological disorders including neurotoxicity induced by environmental stressors such as drugs, environmental contaminants, and dietary factors. We propose that the gut microbiome remotely senses and regulates CNS signaling through the following mechanisms: 1) intestinal bacteria-mediated biotransformation of neurotoxicants that alters the neuro-reactivity of the parent compounds; 2) altered production of neuro-reactive microbial metabolites following exposure to certain environmental stressors; 3) bi-directional communication within the gut-brain axis to alter the intestinal barrier integrity; and 4) regulation of mucosal immune function. Distinct microbial metabolites may enter systemic circulation and epigenetically reprogram the expression of host genes in the CNS, regulating neuroinflammation, cell survival, or cell death. We will also review the current tools for the study of the gut-brain axis and provide some suggestions to move this field forward in the future.
越来越多的人认识到，肠道微生物群是神经系统功能的重要调节者。这篇综述总结了肠道微生物群在各种神经疾病中的作用，包括环境应激源（如药物、环境污染物和饮食因素）引起的神经毒性。我们提出，肠道微生物群通过以下机制远程感知和调节中枢神经系统信号：1）肠道细菌介导的神经毒性物质的生物转化，改变母体化合物的神经反应性；2）暴露于某些环境应激源后，神经反应性微生物代谢物的产生发生改变；3）在肠-脑轴内的双向通讯，改变肠道屏障的完整性；4）调节粘膜免疫功能。不同的微生物代谢物可能进入体循环，并在中枢神经系统中表观遗传地上调宿主基因的表达，调节神经炎症、细胞存活或细胞死亡。我们还将回顾目前用于研究肠-脑轴的工具，并为未来推动这一领域的发展提供一些建议。
