按语(Abstract的Google翻译)：
在过去10年中，对肠道微生物组在调节脑功能中作用的研究迅速增加，但主要集中在动物模型研究。越来越多的临床和临床前证据提示，微生物组可能是神经系统疾病的主要易感因素，包括阿尔茨海默病，自闭症谱系障碍，多发性硬化，帕金森病和中风等。横断面临床研究支持改变微生物的概念有助于此类疾病的病理生理的成分。但是，该领域是新生事物，对于微生物组的组成受多种因素（例如饮食）的影响，此类数据通常很难准确获取。需要进行针对人类的纵向研究和随机对照试验，以确定是否靶向微生物组可以产生新的治疗策略。系统生物学方法在整合中也将很重要此类数据与来自神经疾病的临床队列的基因组和代谢组学数据集有关，以帮助指导个别治疗选择。
与AD相关的文字：
Alzheimer’s disease Despite much disappointment in drug discovery for Alzheimer’s disease over the past decade, there has been some excitement with the possibility that gut microbes have a role in the disease. Although not a new concept, several studies suggest a possible microbial origin for Alzheimer’s disease. The concept that amyloid might act as an antimicrobial peptide in the brain has been an intriguing one, backed up by seminal experimental evidence. However, proving that there is an infective cause to the neuroinflammation and neurodegeneration seen in patients with Alzheimer’s disease is logistically and ethically challenging in humans. As in Parkinson’s disease, the relationship between gut proteins and cognitive health has received increased attention, showing that amyloid-like proteins can be produced by bacteria and increase α-synuclein pathology in vagotomised older rats. However, confirma tion in patients with Parkinson’s disease is outstanding. Cross-sectional studies have identified that the escherichia and shigella bacterial taxa, which are associated with mediating inflammation, are increased in faecal samples from patients with Alzheimer’s disease compared with healthy individuals (table). Moreover, the microbiota changes in patients with Alzheimer’s disease were associated with pro-inflammatory cytokine concentrations in unstimulated and non-centrifuged blood from these patients. The increased abundance of pro-inflammatory Escherichia and Shigella, and a reduction in the abundance of anti-inflammatory Escherichia rectale being possibly associated with a peripheral inflammatory state in patients with cognitive impairment and brain amyloidosis, suggest a link between dysregulation of the microbiota and systemic inflammation, which might initiate or exacerbate the neurodegeneration that occurs in the brain of patients with Alzheimer’s disease. However, it is important to note that these results are from small studies and that longitudinal research is needed in larger cohorts to assess microbiota involvement in the progression of, and its causal relationship with, Alzheimer’s disease. In parallel, transgenic mouse models of Alzheimer’s disease have been shown to have altered microbiota.
Seminal studies in germ-free mice showed that there is a marked absence of amyloid plaque build-up and neuroinflammation when microbes are not present. Similarly, chronic treatment of transgenic mice with an antibiotic cocktail reduced microglia and astrocyte accumulation around amyloid plaques in the hippocampus, and decreased insoluble amyloid βplaques. Together,these studies highlight that the micro biota has a role in regulating key molecular components of Alzheimer’s disease.
google翻译：
阿尔茨海默氏病尽管过去十年来人们对阿尔茨海默氏病的药物发现感到失望，但人们仍对肠道微生物在疾病中起作用的可能性感到兴奋。尽管不是一个新概念，但多项研究表明，可能是阿尔茨海默氏病的微生物起源。淀粉样蛋白可能在大脑中起抗菌肽的作用是一个有趣的概念，并得到了开创性的实验证据的支持。然而，证明对阿尔茨海默氏病患者的神经炎症和神经退行性疾病有感染性，这在人类的逻辑和伦理学上具有挑战性。与帕金森氏病一样，肠道蛋白与认知健康之间的关系受到了越来越多的关注，这表明在迷走了阴道的老年大鼠中细菌可以产生淀粉样蛋白，并增加α-突触核蛋白的病理学。但是，帕金森氏病患者的确诊率很高。横断面研究发现，与健康个体相比，患有阿尔茨海默氏病患者的粪便样本中与介导炎症相关的大肠埃希菌和志贺氏菌类群有所增加（表）。此外，阿尔茨海默氏病患者的微生物群变化与这些患者未经刺激和未经离心的血液中促炎性细胞因子浓度有关。认知障碍和脑淀粉样变性患者的促炎埃希氏菌和志贺氏菌丰富度增加，以及抗炎埃希氏菌丰富度的降低可能与周围炎症状态有关，这表明微生物群失调与全身性失调之间存在联系炎症，可能会引发或加剧阿尔茨海默病患者大脑中发生的神经变性。但是，重要的是要注意，这些结果来自小型研究，并且较大的队列需要进行纵向研究，以评估微生物群参与阿尔茨海默氏病的发展及其与疾病之间的因果关系。同时，已证明阿尔茨海默氏病的转基因小鼠模型改变了微生物群。
在无菌小鼠中进行的开创性研究表明，当不存在微生物时，淀粉样蛋白斑块的积聚和神经发炎明显缺乏。同样，用抗生素混合物对转基因小鼠进行长期治疗可减少海马区淀粉样斑块周围的小胶质细胞和星形胶质细胞积聚，并减少不溶性淀粉样蛋白β斑块。这些研究共同强调了微生物群在调节阿尔茨海默氏病关键分子成分中的作用。
国内耿美玉教授团队的创新性研究成果：https://mp.weixin.qq.com/s/nv8bkjkJf4CJCwlz1rifTA
综述原文出处：
Lancet Neurol 2019Published OnlineNovember 18, 2019https://doi.org/10.1016/S1474-4422(19)30356-4
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