Benichou Haziot Carla, Birak Kulbir Singh
Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
J Alzheimers Dis Rep. 2023 May 12;7(1):415-431. doi: 10.3233/ADR-220097. eCollection 2023.
Alzheimer's disease (AD) is the most common neurodegenerative disease, yet it currently lacks effective treatment due to its complex etiology. The pathological changes in AD have been linked to the neurotoxic immune responses following aggregation of Aβ and phosphorylated tau. The gut microbiota (GM) is increasingly studied for modulating neuroinflammation in neurodegenerative diseases and studies emerge for AD. This critical review selected 7 empirical preclinical studies from 2019 onwards assessing therapy approaches targeting GM modulating microglia neuroinflammation in AD mouse models. Results from probiotics, fecal microbiota transplantation, and drugs were compared and contrasted, including for cognition, neuroinflammation, and toxic aggregation of proteins. Studies consistently reported significant amelioration or prevention of cognitive deficits, decrease in microglial activation, and lower levels of pro-inflammatory cytokines, compared to AD mouse models. However, there were differences across papers for the brain regions affected, and changes in astrocytes were inconsistent. Aβ plaques deposition significantly decreased in all papers, apart from Byur dMar Nyer lNga Ril Bu () treatment. Tau phosphorylation significantly declined in 5 studies. Effects in microbial diversity following treatment varied across studies. Findings are encouraging regarding the efficacy of study but information on the effect size is limited. Potentially, GM reverses GM derived abnormalities, decreasing neuroinflammation, which reduces AD toxic aggregations of proteins in the brain, resulting in cognitive improvements. Results support the hypothesis of AD being a multifactorial disease and the potential synergies through multi-target approaches. The use of AD mice models limits conclusions around effectiveness, as human translation is challenging.
阿尔茨海默病（AD）是最常见的神经退行性疾病，但由于其病因复杂，目前缺乏有效的治疗方法。AD的病理变化与Aβ和磷酸化tau蛋白聚集后的神经毒性免疫反应有关。肠道微生物群（GM）在神经退行性疾病中调节神经炎症的作用越来越受到研究，针对AD的研究也不断涌现。这篇批判性综述选取了2019年以来的7项实证性临床前研究，评估了针对GM调节AD小鼠模型中小胶质细胞神经炎症的治疗方法。对益生菌、粪便微生物群移植和药物的结果进行了比较和对比，包括对认知、神经炎症和蛋白质毒性聚集的影响。与AD小鼠模型相比，研究一致报告认知缺陷得到显著改善或预防、小胶质细胞活化减少以及促炎细胞因子水平降低。然而，不同论文中受影响的脑区存在差异，星形胶质细胞的变化也不一致。除了Byur dMar Nyer lNga Ril Bu（）治疗外，所有论文中Aβ斑块沉积均显著减少。5项研究中tau蛋白磷酸化显著下降。治疗后微生物多样性的影响因研究而异。研究结果在疗效方面令人鼓舞，但关于效应大小的信息有限。GM有可能逆转GM衍生的异常，减少神经炎症，从而减少大脑中AD的蛋白质毒性聚集，导致认知改善。结果支持AD是一种多因素疾病的假设以及通过多靶点方法实现潜在协同作用的观点。使用AD小鼠模型限制了关于有效性的结论，因为向人类的转化具有挑战性。
