Lee Mijung, Lee So-Hee, Kim Min-Soo, Ahn Kwang-Sung, Kim Manho
Department of Neurology, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.
Functional Genome Institute, PDXen. Biosystem Co., Gyeongi-do, Republic of Korea.
J Ginseng Res. 2022 May;46(3):464-472. doi: 10.1016/j.jgr.2021.11.001. Epub 2021 Nov 11.
Gut microbiota influence the central nervous system through gut-brain-axis. They also affect the neurological disorders. Gut microbiota differs in patients with Alzheimer's disease (AD), as a potential factor that leads to progression of AD. Oral intake of Korean Red Ginseng (KRG) improves the cognitive functions. Therefore, it can be proposed that KRG affect the microbiota on the gut-brain-axis to the brain.
Tg2576 were used for the experimental model of AD. They were divided into four groups: wild type (n = 6), AD mice (n = 6), AD mice with 30 mg/kg/day (n = 6) or 100 mg/kg/day (n = 6) of KRG. Following two weeks, changes in gut microbiota were analyzed by Illumina HiSeq4000 platform 16S gene sequencing. Microglial activation were evaluated by quantitative Western blot analyses of Iba-1 protein. Claudin-5, occludin, laminin and CD13 assay were conducted for Blood-brain barrier (BBB) integrity. Amyloid beta (Aβ) accumulation demonstrated through Aβ 42/40 ratio was accessed by ELISA, and cognition were monitored by Novel object location test.
KRG improved the cognitive behavior of mice (30 mg/kg/day p < 0.05; 100 mg/kg/day p < 0.01), and decreased Aβ 42/40 ratio (p < 0.01) indicating reduced Aβ accumulation. Increased Iba-1 (p < 0.001) for reduced microglial activation, and upregulation of Claudin-5 (p < 0.05) for decreased BBB permeability were shown. In particular, diversity of gut microbiota was altered (30 mg/kg/day q-value<0.05), showing increased population of Lactobacillus species. (30 mg/kg/day 411%; 100 mg/kg/day 1040%).
KRG administration showed the Lactobacillus dominance in the gut microbiota. Improvement of AD pathology by KRG can be medicated through gut-brain axis in mice model of AD.
肠道微生物群通过肠-脑轴影响中枢神经系统，也会影响神经紊乱。阿尔茨海默病（AD）患者的肠道微生物群存在差异，这是导致AD病情进展的一个潜在因素。口服韩国红参（KRG）可改善认知功能。因此，可以推测KRG会影响肠-脑轴上的微生物群对大脑的作用。
使用Tg2576作为AD的实验模型。将它们分为四组：野生型（n = 6）、AD小鼠（n = 6）、接受30 mg/kg/天（n = 6）或100 mg/kg/天（n = 6）KRG的AD小鼠。两周后，通过Illumina HiSeq4000平台16S基因测序分析肠道微生物群的变化。通过对Iba-1蛋白进行定量蛋白质免疫印迹分析来评估小胶质细胞的激活情况。对血脑屏障（BBB）的完整性进行紧密连接蛋白-5、闭合蛋白、层粘连蛋白和CD13检测。通过ELISA检测淀粉样β蛋白（Aβ）42/40比值来评估Aβ的积累情况，并通过新物体定位试验监测认知情况。
KRG改善了小鼠的认知行为（30 mg/kg/天，p < 0.05；100 mg/kg/天，p < 0.01），并降低了Aβ 42/40比值（p < 0.01），表明Aβ积累减少。显示Iba-1增加（p < 0.001），表明小胶质细胞激活减少，紧密连接蛋白-5上调（p < 0.05），表明BBB通透性降低。特别是，肠道微生物群的多样性发生了改变（30 mg/kg/天，q值<0.05），显示乳酸杆菌属的数量增加（30 mg/kg/天，增加411%；100 mg/kg/天，增加1040%）。
给予KRG后，肠道微生物群中乳酸杆菌占优势。在AD小鼠模型中，KRG对AD病理的改善可通过肠-脑轴实现。
