Abstract Alzheimer's disease (AD) is the most prevalent neurodegenerative disease, and is characterized by the accumulation and presence of amyloid plaques (Aβ), tangles, dementia, and cognitive impairment. Currently, there is no known cure for AD; however, recently, the association between alteration of the gut microbiota and AD pathology has been explored to find novel therapeutic approaches. Microbiota-targeted intervention has been suggested as an attractive therapeutic approach for AD. Agathobaculum butyriciproducens (SR79) is a strict anaerobic and butyric acid-producing bacteria. We hypothesized that administration of SR79 might have a beneficial effect on cognitive deficits and AD pathologies. To determine the therapeutic effects of SR79 on AD pathologies, APP/PS1 transgenic and LPS-induced cognitive impairment mouse models were used. In the LPS-induced cognitive deficit model, the administration of SR79 improved cognitive function and decreased microglia activation. In addition, the administration of SR79 to APP/PS1 mice significantly improved novel object recognition and percent alteration results in novel object recognition and Y-maze alteration tests. Furthermore, Aβ plaque deposition and microglial activation were markedly reduced in the parietal cortex and hippocampus after SR79 treatment in APP/PS1 mice. SR79 treatment significantly decreased gene expression levels of IL-1β and C1QB and increased the gene expression levels of IGF-1 and thereby the downstream signaling pathway in the cortex of APP/PS1 mice. In conclusion, SR79 administration improved cognitive function and AD pathologies through the regulation of neuroinflammation and IGF-1 signaling in an animal model.

中文翻译：

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人类肠道微生物群 Agathobaculum butyriciproducens 改善 LPS 诱导和 APP/PS1 阿尔茨海默病小鼠模型的认知障碍

摘要 阿尔茨海默病 (AD) 是最普遍的神经退行性疾病，其特征是淀粉样蛋白斑 (Aβ)、缠结、痴呆和认知障碍的积累和存在。目前，没有已知的治疗 AD 的方法。然而，最近，已经探索了肠道微生物群的改变与 AD 病理之间的关联，以寻找新的治疗方法。微生物群靶向干预被认为是一种有吸引力的 AD 治疗方法。Agathobaculum butyriciproducens (SR79) 是一种严格的厌氧产丁酸细菌。我们假设施用 SR79 可能对认知缺陷和 AD 病理产生有益影响。为了确定 SR79 对 AD 病理的治疗效果，使用了 APP/PS1 转基因和 LPS 诱导的认知障碍小鼠模型。在 LPS 诱导的认知缺陷模型中，SR79 的给药改善了认知功能并减少了小胶质细胞的激活。此外，向 APP/PS1 小鼠施用 SR79 显着改善了新物体识别和新物体识别和 Y 迷宫改变测试中的百分比改变结果。此外，在 APP/PS1 小鼠的 SR79 处理后，顶叶皮层和海马中的 Aβ 斑块沉积和小胶质细胞活化显着减少。SR79 处理显着降低了 IL-1β 和 C1QB 的基因表达水平，并增加了 IGF-1 的基因表达水平，从而增加了 APP/PS1 小鼠皮层中的下游信号通路。总之，SR79 给药通过调节动物模型中的神经炎症和 IGF-1 信号传导改善了认知功能和 AD 病理。