Unit of Pharmacology and Pharmacovigilance, Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 55, 56126, Pisa, Italy.
Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35131, Padova, Italy.
Acta Neuropathol. 2018 Sep;136(3):345-361. doi: 10.1007/s00401-018-1856-5. Epub 2018 May 24.
Neurological diseases, such as Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis (ALS) and multiple sclerosis, are often associated with functional gastrointestinal disorders. These gastrointestinal disturbances may occur at all stages of the neurodegenerative diseases, to such an extent that they are now considered an integral part of their clinical picture. Several lines of evidence support the contention that, in central neurodegenerative diseases, changes in gut microbiota and enteric neuro-immune system alterations could contribute to gastrointesinal dysfunctions as well as initiation and upward spreading of the neurologic disorder. The present review has been intended to provide a comprehensive overview of the available knowledge on the role played by enteric microbiota, mucosal immune system and enteric nervous system, considered as an integrated network, in the pathophysiology of the main neurological diseases known to be associated with intestinal disturbances. In addition, based on current human and pre-clinical evidence, our intent was to critically discuss whether changes in the dynamic interplay between gut microbiota, intestinal epithelial barrier and enteric neuro-immune system are a consequence of the central neurodegeneration or might represent the starting point of the neurodegenerative process. Special attention has been paid also to discuss whether alterations of the enteric bacterial-neuro-immune network could represent a common path driving the onset of the main neurodegenerative diseases, even though each disease displays its own distinct clinical features.
神经疾病，如帕金森病、阿尔茨海默病、肌萎缩侧索硬化症（ALS）和多发性硬化症，常与功能性胃肠疾病有关。这些胃肠道紊乱可能发生在神经退行性疾病的所有阶段，以至于它们现在被认为是其临床特征的一个组成部分。有几条证据支持这样一种观点，即在中枢神经退行性疾病中，肠道微生物群的变化和肠神经免疫系统的改变可能导致胃肠道功能障碍，以及神经紊乱的起始和向上传播。本综述旨在全面概述肠道微生物群、黏膜免疫系统和肠神经免疫系统作为一个整合网络在已知与肠道紊乱相关的主要神经疾病的病理生理学中的作用。此外，基于目前的人体和临床前证据，我们旨在批判性地讨论肠道微生物群、肠道上皮屏障和肠神经免疫系统之间的动态相互作用的变化是中枢神经退行性变的结果，还是可能代表神经退行性过程的起点。我们还特别关注讨论肠道细菌-神经-免疫网络的改变是否可能代表驱动主要神经退行性疾病发生的共同途径，尽管每种疾病都有其自身独特的临床特征。
