按語(yǔ)(Abstract的Google翻譯)：

在過(guò)去10年中，對(duì)腸道微生物組在調(diào)節(jié)腦功能中作用的研究迅速增加，但主要集中在動(dòng)物模型研究。越來(lái)越多的臨床和臨床前證據(jù)提示，微生物組可能是神經(jīng)系統(tǒng)疾病的主要易感因素，包括阿爾茨海默病，自閉癥譜系障礙，多發(fā)性硬化，帕金森病和中風(fēng)等。橫斷面臨床研究支持改變微生物的概念有助于此類疾病的病理生理的成分。但是，該領(lǐng)域是新生事物，對(duì)于微生物組的組成受多種因素（例如飲食）的影響，此類數(shù)據(jù)通常很難準(zhǔn)確獲取。需要進(jìn)行針對(duì)人類的縱向研究和隨機(jī)對(duì)照試驗(yàn)，以確定是否靶向微生物組可以產(chǎn)生新的治療策略。系統(tǒng)生物學(xué)方法在整合中也將很重要此類數(shù)據(jù)與來(lái)自神經(jīng)疾病的臨床隊(duì)列的基因組和代謝組學(xué)數(shù)據(jù)集有關(guān)，以幫助指導(dǎo)個(gè)別治療選擇。

與AD相關(guān)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翻譯：

阿爾茨海默氏病盡管過(guò)去十年來(lái)人們對(duì)阿爾茨海默氏病的藥物發(fā)現(xiàn)感到失望，但人們?nèi)詫?duì)腸道微生物在疾病中起作用的可能性感到興奮。盡管不是一個(gè)新概念，但多項(xiàng)研究表明，可能是阿爾茨海默氏病的微生物起源。淀粉樣蛋白可能在大腦中起抗菌肽的作用是一個(gè)有趣的概念，并得到了開(kāi)創(chuàng)性的實(shí)驗(yàn)證據(jù)的支持。然而，證明對(duì)阿爾茨海默氏病患者的神經(jīng)炎癥和神經(jīng)退行性疾病有感染性，這在人類的邏輯和倫理學(xué)上具有挑戰(zhàn)性。與帕金森氏病一樣，腸道蛋白與認(rèn)知健康之間的關(guān)系受到了越來(lái)越多的關(guān)注，這表明在迷走了陰道的老年大鼠中細(xì)菌可以產(chǎn)生淀粉樣蛋白，并增加α-突觸核蛋白的病理學(xué)。但是，帕金森氏病患者的確診率很高。橫斷面研究發(fā)現(xiàn)，與健康個(gè)體相比，患有阿爾茨海默氏病患者的糞便樣本中與介導(dǎo)炎癥相關(guān)的大腸埃希菌和志賀氏菌類群有所增加（表）。此外，阿爾茨海默氏病患者的微生物群變化與這些患者未經(jīng)刺激和未經(jīng)離心的血液中促炎性細(xì)胞因子濃度有關(guān)。認(rèn)知障礙和腦淀粉樣變性患者的促炎埃希氏菌和志賀氏菌豐富度增加，以及抗炎埃希氏菌豐富度的降低可能與周圍炎癥狀態(tài)有關(guān)，這表明微生物群失調(diào)與全身性失調(diào)之間存在聯(lián)系炎癥，可能會(huì)引發(fā)或加劇阿爾茨海默病患者大腦中發(fā)生的神經(jīng)變性。但是，重要的是要注意，這些結(jié)果來(lái)自小型研究，并且較大的隊(duì)列需要進(jìn)行縱向研究，以評(píng)估微生物群參與阿爾茨海默氏病的發(fā)展及其與疾病之間的因果關(guān)系。同時(shí)，已證明阿爾茨海默氏病的轉(zhuǎn)基因小鼠模型改變了微生物群。

在無(wú)菌小鼠中進(jìn)行的開(kāi)創(chuàng)性研究表明，當(dāng)不存在微生物時(shí)，淀粉樣蛋白斑塊的積聚和神經(jīng)發(fā)炎明顯缺乏。同樣，用抗生素混合物對(duì)轉(zhuǎn)基因小鼠進(jìn)行長(zhǎng)期治療可減少海馬區(qū)淀粉樣斑塊周圍的小膠質(zhì)細(xì)胞和星形膠質(zhì)細(xì)胞積聚，并減少不溶性淀粉樣蛋白β斑塊。這些研究共同強(qiáng)調(diào)了微生物群在調(diào)節(jié)阿爾茨海默氏病關(guān)鍵分子成分中的作用。

國(guó)內(nèi)耿美玉教授團(tuán)隊(duì)的創(chuàng)新性研究成果：https://mp.weixin.qq.com/s/nv8bkjkJf4CJCwlz1rifTA

綜述原文出處：

Lancet Neurol 2019Published OnlineNovember 18, 2019https:///10.1016/S1474-4422(19)30356-4