The number of bacterial cells living within the human body is approximately equal to, or greater than, the total number of human cells. This dynamic population of microorganisms, termed the human microbiota, resides mainly within the gastrointestinal tract. It is widely accepted that highly diverse and stable microbiota promote overall human health. Colonization of the gut with maladaptive and pathogenic microbiota, a state also known as dysbiosis, is associated with a variety of peripheral diseases ranging from type 2 diabetes mellitus to cardiovascular and inflammatory bowel disease. More recently, microbial dysbiosis has been associated with a number of brain pathologies, including autism spectrum disorder, Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), suggesting a direct or indirect communication between intestinal bacteria and the central nervous system (CNS). In this review, we illustrate two pathways implicated in the crosstalk between gut microbiota and CNS involving 1) the vagus nerve and 2) transmission of signaling molecules through the circulatory system and across the blood-brain barrier (BBB). We summarize the available evidence of the specific changes in the intestinal microbiota, as well as microorganism-induced modifications to intestinal and BBB permeability, which have been linked to several neurodegenerative disorders including ALS, AD, and PD. Even though each of these diseases arises from unique pathogenetic mechanisms, all are characterized, at least in part, by chronic neuroinflammation. We provide an interpretation for the substantial evidence that healthy intestinal microbiota have the ability to positively regulate the neuroimmune responses in the CNS. Even though the evidence is mainly associative, it has been suggested that bacterial dysbiosis could contribute to an adverse neuroinflammatory state leading to increased risk of neurodegenerative diseases. Thus, developing strategies for regulating and maintaining healthy intestinal microbiota could be a valid approach for lowering individual risk and prevalence of neurodegenerative diseases.

生活在人体中的细菌细胞的数量大约等于或大于人体细胞的总数。这种动态的微生物种群（称为人类微生物群）主要位于胃肠道内。高度多样化和稳定的微生物群可以促进人类整体健康，这一点已被广泛接受。肠道因适应不良和致病性微生物群而定居，这种状态也被称为营养不良，与从2型糖尿病到心血管和炎症性肠病等多种周围疾病有关。最近，微生物营养不良与许多脑部疾病相关，包括自闭症谱系障碍，阿尔茨海默氏病（AD），帕金森氏病（PD）和肌萎缩性侧索硬化症（ALS），提示肠道细菌与中枢神经系统（CNS）之间存在直接或间接的交流。在这篇综述中，我们说明了肠道微生物群和中枢神经系统之间的串扰涉及的两个途径，涉及1）迷走神经和2）信号分子通过循环系统和血脑屏障（BBB）的传递。我们总结了肠道微生物群发生特定变化的现有证据，以及微生物诱导的肠道和BBB通透性的修饰，这些修饰已与包括ALS，AD和PD在内的几种神经退行性疾病相关。即使这些疾病中的每一种都是由独特的致病机制引起的，但所有这些疾病的特征至少部分是慢性神经炎症。我们为健康肠道微生物群具有积极调节中枢神经系统神经免疫反应能力的大量证据提供了解释。即使证据主要是关联性的，也已表明细菌性营养不良可能导致不良的神经炎症状态，导致神经退行性疾病的风险增加。因此，制定用于调节和维持健康肠道菌群的策略可能是降低个人风险和神经退行性疾病患病率的有效方法。