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通过高通量测序技术探索安理申对轻度阿尔茨海默病患者肠道菌群多样性的影响。

Effects of Aricept on intestinal flora diversity in patients with mild Alzheimer's disease explored through high-throughput sequencing technology.

作者信息

Jiang Yang, Guo Zhongwei, Liu Xuezhen, Wang Yanping, Li Jiapeng, Wang Bin

机构信息

Department of Science and Education, Tongde Hospital of Zhejiang Province Hangzhou, Zhejiang Province, China.

Department of Geriatrics, Tongde Hospital of Zhejiang Province Hangzhou, Zhejiang Province, China.

出版信息

Am J Transl Res. 2021 Apr 15;13(4):2486-2498. eCollection 2021.

Abstract

OBJECTIVE

To research the effects of Aricept on the intestinal flora in patients with mild Alzheimer's disease (AD) and explore the relationship between the improvement from Aricept on AD and the changes in intestinal flora.

METHODS

One month after Aricept treatment, DNA was extracted from stool samples of patients and the quality of DNA was detected. Then, the library was constructed, quantified, pooled and the quality of the library was checked. Sequencing was conducted using the Miseq sequencer and the related results were analyzed by bioinformatics.

RESULTS

The overall structure of intestinal flora in AD patients was largely changed after Aricept treatment (P<0.05), which was mainly shown as decreased abundance of Firmicutes, Proteobacteria, actinobacteria and fusobacteria, and increased abundance of Bacteroidetes. The average abundance of intestinal flora in lipid metabolism pathwa was also different before and after treatment (P<0.05). The function of target receptor molecules in the Aricept drug target network mainly targets G-protein coupled receptors; biological processes in energy metabolism; and biological pathways mostly target proteoglycans.

CONCLUSION

The occurrence and progression of AD are closely related to abnormal changes in intestinal flora structure. Bile acids may improve the symptoms of mild AD by changing the intestinal flora through lipid energy metabolism. In other words, Bile acids regulate the activity of the host nervous system through intestinal flora regulation. Intestinal flora maintains the homeostasis of bile acid and further affects the physiological and pathological processes of the host. The analysis of AD related flora structure pattern helps to understand the molecular pathological basis of AD and provides theoretical basis for the development and design of innovative drugs for AD.

摘要

目的

研究多奈哌齐对轻度阿尔茨海默病(AD)患者肠道菌群的影响,并探讨多奈哌齐对AD的改善作用与肠道菌群变化之间的关系。

方法

多奈哌齐治疗1个月后,从患者粪便样本中提取DNA并检测其质量。然后构建文库、定量、合并并检查文库质量。使用Miseq测序仪进行测序,并通过生物信息学分析相关结果。

结果

多奈哌齐治疗后,AD患者肠道菌群的整体结构发生了很大变化(P<0.05),主要表现为厚壁菌门、变形菌门、放线菌门和梭杆菌门的丰度降低,拟杆菌门的丰度增加。脂质代谢途径中肠道菌群的平均丰度在治疗前后也有所不同(P<0.05)。多奈哌齐药物靶点网络中的靶受体分子功能主要靶向G蛋白偶联受体;能量代谢中的生物学过程;生物学途径大多靶向蛋白聚糖。

结论

AD的发生和进展与肠道菌群结构的异常变化密切相关。胆汁酸可能通过脂质能量代谢改变肠道菌群来改善轻度AD的症状。换句话说,胆汁酸通过调节肠道菌群来调节宿主神经系统的活性。肠道菌群维持胆汁酸的稳态,并进一步影响宿主的生理和病理过程。对AD相关菌群结构模式的分析有助于理解AD的分子病理基础,并为AD创新药物的开发和设计提供理论依据。

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