Li Yuan, Wu Mengyao, Kong Mengmeng, Sui Shaomei, Wang Qi, He Yan, Gu Jinsong
School of Biological Science and Technology, University of Jinan, Jinan 250022, China.
Department of Neurology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan 250014, China.
Microorganisms. 2023 Sep 13;11(9):2306. doi: 10.3390/microorganisms11092306.
Based on published information, the occurrence and development of Alzheimer's disease (AD) are potentially related to gut microbiota changes. Donepezil hydrochloride (DH), which enhances cholinergic activity by blocking acetylcholinesterase (AChE), is one of the first-line drugs for AD treatment approved by the Food and Drug Administration (FDA) of the USA. However, the potential link between the effects of DH on the pathophysiological processes of AD and the gut microbiota remains unclear. In this study, pathological changes in the brain and colon, the activities of superoxide dismutase (SOD) and AChE, and changes in intestinal flora were observed. The results showed that Aβ deposition in the prefrontal cortex and hippocampus of AD mice was significantly decreased, while colonic inflammation was significantly alleviated by DH treatment. Concomitantly, SOD activity was significantly improved, while AChE was significantly reduced after DH administration. In addition, the gut microbiota community composition of AD mice was significantly altered after DH treatment. The relative abundance of in the AD group was 54.8% higher than that in the N group. The relative abundance of was increased by 18.3% and 53.8% in the AD_G group and the N_G group, respectively. Interestingly, showed a potential predictive value and might be a biomarker for AD. Molecular docking revealed the binding mode and major forces between DH and membrane proteins of . The overall results suggest a novel therapeutic mechanism for treating AD and highlight the critical role of gut microbiota in AD pathology.
根据已发表的信息，阿尔茨海默病（AD）的发生和发展可能与肠道微生物群的变化有关。盐酸多奈哌齐（DH）通过抑制乙酰胆碱酯酶（AChE）来增强胆碱能活性，是美国食品药品监督管理局（FDA）批准的用于AD治疗的一线药物之一。然而，DH对AD病理生理过程的影响与肠道微生物群之间的潜在联系仍不清楚。在本研究中，观察了大脑和结肠的病理变化、超氧化物歧化酶（SOD）和AChE的活性以及肠道菌群的变化。结果表明，DH治疗可显著降低AD小鼠前额叶皮质和海马中的Aβ沉积，同时显著减轻结肠炎症。同时，DH给药后SOD活性显著提高，而AChE活性显著降低。此外，DH治疗后AD小鼠的肠道微生物群群落组成发生了显著改变。AD组中[具体菌种名称未给出]的相对丰度比N组高54.8%。AD_G组和N_G组中[具体菌种名称未给出]的相对丰度分别增加了18.3%和53.8%。有趣的是，[具体菌种名称未给出]显示出潜在的预测价值，可能是AD的一个生物标志物。分子对接揭示了DH与[具体菌种名称未给出]膜蛋白之间的结合模式和主要作用力。总体结果提示了一种治疗AD的新机制，并突出了肠道微生物群在AD病理学中的关键作用。
