按語(Abstract的Google翻譯)：
在過去10年中，對腸道微生物組在調節腦功能中作用的研究迅速增加，但主要集中在動物模型研究。越來越多的臨床和臨床前證據提示，微生物組可能是神經系統疾病的主要易感因素，包括阿爾茨海默病，自閉症譜系障礙，多發性硬化，帕金森病和中風等。橫斷面臨床研究支持改變微生物的概念有助於此類疾病的病理生理的成分。但是，該領域是新生事物，對於微生物組的組成受多種因素（例如飲食）的影響，此類數據通常很難準確獲取。需要進行針對人類的縱向研究和隨機對照試驗，以確定是否靶向微生物組可以產生新的治療策略。系統生物學方法在整合中也將很重要此類數據與來自神經疾病的臨床隊列的基因組和代謝組學數據集有關，以幫助指導個別治療選擇。
與AD相關的文字：
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.
翻譯：
阿爾茨海默氏病儘管過去十年來人們對阿爾茨海默氏病的藥物發現感到失望，但人們仍對腸道微生物在疾病中起作用的可能性感到興奮。儘管不是一個新概念，但多項研究表明，可能是阿爾茨海默氏病的微生物起源。澱粉樣蛋白可能在大腦中起抗菌肽的作用是一個有趣的概念，並得到了開創性的實驗證據的支持。然而，證明對阿爾茨海默氏病患者的神經炎症和神經退行性疾病有感染性，這在人類的邏輯和倫理學上具有挑戰性。與帕金森氏病一樣，腸道蛋白與認知健康之間的關係受到了越來越多的關注，這表明在迷走了陰道的老年大鼠中細菌可以產生澱粉樣蛋白，並增加α-突觸核蛋白的病理學。但是，帕金森氏病患者的確診率很高。橫斷面研究發現，與健康個體相比，患有阿爾茨海默氏病患者的糞便樣本中與介導炎症相關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刺激和未經離心的血液中促炎性細胞因子濃度有關。認知障礙和腦澱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症狀態有關，這表明微生物群失調與全身性失調之間存在聯繫炎症，可能會引發或加劇阿爾茨海默病患者大腦中發生的神經變性。但是，重要的是要注意，這些結果來自小型研究，並且較大的隊列需要進行縱向研究，以評估微生物群參與阿爾茨海默氏病的發展及其與疾病之間的因果關係。同時，已證明阿爾茨海默氏病的轉基因小鼠模型改變了微生物群。
在無菌小鼠中進行的開創性研究表明，當不存在微生物時，澱粉樣蛋白斑塊的積聚和神經發炎明顯缺乏。同樣，用抗生素混合物對轉基因小鼠進行長期治療可減少海馬區澱粉樣斑塊周圍的小膠質細胞和星形膠質細胞積聚，並減少不溶性澱粉樣蛋白β斑塊。這些研究共同強調了微生物群在調節阿爾茨海默氏病關鍵分子成分中的作用。
閱讀更多 徐俊主任醫師 的文章
