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.

中文翻译：

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健康微生物群的转移可减少阿尔茨海默病动物模型中的淀粉样蛋白和 tau 蛋白病理

目的脑淀粉样变性和大脑中的严重 tau 蛋白病变是阿尔茨海默病 (AD) 的关键病理特征。尽管肠道微生物群对 AD 有很强的影响，但肠道微生物群与 AD 病理生理学之间的因果关系仍然难以捉摸。设计 使用最近开发的具有淀粉样蛋白和神经原纤维缠结 (ADLPAPT) 转基因 AD 小鼠模型的 AD 样病理学，该模型显示大脑中的淀粉样蛋白斑块、神经原纤维缠结和反应性神经胶质增生以及记忆缺陷，我们检查了肠道微生物群对AD发病机制。结果 ADLPAPT 小鼠肠道微生物群的组成与健康野生型 (WT) 小鼠不同。此外，ADLPAPT 小鼠表现出上皮屏障完整性和慢性肠道和全身炎症的丧失。将 WT 小鼠的粪便微生物群频繁转移和移植到 ADLPAPT 小鼠中，均改善了淀粉样蛋白 β 斑块和神经原纤维缠结、神经胶质反应性和认知障碍的形成。此外，粪便微生物群转移逆转了 ADLPAPT 受体小鼠与肠道巨噬细胞活性和循环血液炎症单核细胞相关基因的结肠表达异常。结论 这些结果表明，微生物群介导的肠道和全身免疫异常有助于 ADLPAPT 小鼠 AD 的发病机制，为肠道（结肠基因表达、肠道通透性）、血液（血液免疫细胞群）和大脑之间的关系提供了新的见解（病理）轴和 AD（记忆缺陷）。因此，