粪菌移植治疗小鼠阿尔兹海默症
创作:鱼儿 审核:aluba 2019年09月08日
  • 建立阿尔兹海默症(AD)的转基因小鼠模型,AD小鼠的脑中出现淀粉样斑块、神经原纤维缠结和反应性胶质增生,并表现出记忆缺陷;
  • 与健康野生型(WT)小鼠相比,AD小鼠表现出肠道菌群组成改变、上皮屏障完整性丧失、慢性肠道和全身炎症;
  • 移植WT小鼠的粪菌给AD小鼠,可改善后者的β淀粉样蛋白斑块沉积、tau蛋白病理学、神经胶质反应和认知障碍;
  • AD小鼠结肠中与肠道巨噬细胞活性及血液炎性单核细胞相关的基因表达异常,粪菌移植可逆转。
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aluba
肠道菌群可能在阿尔兹海默症(AD)中发挥重要作用。来自Gut上发表的一项最新研究中,建立了AD小鼠模型,并发现移植健康小鼠的粪菌可改善AD小鼠的病理及认知,提示肠道菌群与AD发病机制之间存在的潜在因果关联,以及恢复肠道稳态或是治疗AD的潜在策略。
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Gut [IF:31.793]

Transfer of a healthy microbiota reduces amyloid and tau pathology in an Alzheimer’s disease animal model

在阿尔茨海默病动物模型中,移植健康菌群可减少淀粉样蛋白和tau蛋白的病理学

10.1136/gutjnl-2018-317431

2019-08-30, Article

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Objective : Cerebral amyloidosis and severe tauopathy in the brain are key pathological features of Alzheimer’s disease (AD). Despite a strong influence of the intestinal microbiota on AD, the causal relationship between the gut microbiota and AD pathophysiology is still elusive.
Design: Using a recently developed AD-like pathology with amyloid and neurofibrillary tangles (ADLPAPT) transgenic mouse model of AD, which shows amyloid plaques, neurofibrillary tangles and reactive gliosis in their brains along with memory deficits, we examined the impact of the gut microbiota on AD pathogenesis.
Results : Composition of the gut microbiota in ADLPAPT mice differed from that of healthy wild-type (WT) mice. Besides, ADLPAPT mice showed a loss of epithelial barrier integrity and chronic intestinal and systemic inflammation. Both frequent transfer and transplantation of the faecal microbiota from WT mice into ADLPAPT mice ameliorated the formation of amyloid β plaques and neurofibrillary tangles, glial reactivity and cognitive impairment. Additionally, the faecal microbiota transfer reversed abnormalities in the colonic expression of genes related to intestinal macrophage activity and the circulating blood inflammatory monocytes in the ADLPAPT recipient mice.
Conclusion : These results indicate that microbiota-mediated intestinal and systemic immune aberrations contribute to the pathogenesis of AD in ADLPAPT mice, providing new insights into the relationship between the gut (colonic gene expression, gut permeability), blood (blood immune cell population) and brain (pathology) axis and AD (memory deficits). Thus, restoring gut microbial homeostasis may have beneficial effects on AD treatment.

First Authors:
Min-Soo Kim,Yoonhee Kim,Hyunjung Choi

Correspondence Authors:
Jin-Woo Bae,Inhee Mook-Jung

All Authors:
Min-Soo Kim,Yoonhee Kim,Hyunjung Choi,Woojin Kim,Sumyung Park,Dongjoon Lee,Dong Kyu Kim,Haeng Jun Kim,Hayoung Choi,Dong-Wook Hyun,June-Young Lee,Eun Young Choi,Dong-Sup Lee,Jin-Woo Bae,Inhee Mook-Jung

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