A Novel Probiotic Formula, BIOCG, Protects Against Alzheimer's-Related Cognitive Deficits via Regulation of Dendritic Spine Dynamics.
A Novel Probiotic Formula, BIOCG, Protects Against Alzheimer's-Related Cognitive Deficits via Regulation of Dendritic Spine Dynamics.
复制标题
一种新型益生菌配方 BIOCG 通过调节树突棘动力学来预防阿尔茨海默病相关的认知缺陷。
DOI：
10.2174/1567205018666211022091110
复制
发表时间：
2021
影响因子：
2.1
通讯作者：
Xiaofeng Bao
中科院分区：
文献类型：
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作者：
Miao Sun;Wenchenyang Bao;Chen;Ziyue Xia;Changliang Zhang;Guangxian Wang;Runxin Wang;Jiangyu Li;Shaun Roux;Qian Li;Dongmei Zou;Kai Ma;Xiaofeng Bao
背景
大脑-肠道-微生物组轴已成为一条重要途径，肠道和/或微生物微环境的扰动可以通过该途径影响神经功能。这种改变与多种神经精神疾病有关，包括抑郁症、焦虑症和阿尔茨海默病（AD），使用益生菌治疗这些疾病仍然有希望。然而，肠道微环境影响疾病发病机制和治疗的机制仍不清楚。
目标
本研究的目的是在 AD 小鼠模型中研究新型益生菌配方 BIOCG 对认知功能和病理生物学机制（包括淀粉样蛋白加工和树突棘动力学）的影响。
方法
BIOCG施用3个月至3xTg或3xTg；通过行为测试和电生理学评估 Thy1-YFP AD 小鼠和功能结果。还评估了与 AD 发病机制相关的机制，包括树突棘形态和周转、淀粉样前体蛋白 (APP) 加工和小胶质细胞表型。最后，我们对益生菌治疗后的粪便样本进行了测序，以评估对肠道微生物组成的影响，并将变化与上述措施联系起来。
结果
用 BIOCG 治疗的小鼠表现出保留的认知能力和更强的长时程增强 (LTP)、自发兴奋性突触后电流 (sEPSC) 和谷氨酸诱导的 LTP，表明功能和电生理效应。此外，我们观察到 AD 发病机制减弱，包括β淀粉样蛋白 (Aβ) 负担减少，以及 BIOCG 治疗后树突棘更加成熟。我们对治疗组中小胶质细胞数量和表型变化的发现表明，该制剂可能通过减弱神经炎症来介导其作用。测序数据证实，接受治疗的小鼠的肠道微生物群更加多样化，并且含有更大比例的“有益”细菌。
结论
总体而言，我们的结果表明，BIOCG 治疗可增强微生物多样性，并通过肠-脑轴相互作用减轻神经炎症，从而改善 AD 发病机制的组织学和功能。
BACKGROUND
The brain-gut-microbiome axis has emerged as an important pathway through which perturbations in the gut and/or microbial microenvironment can impact neurological function. Such alterations have been implicated in a variety of neuropsychiatric disorders, includ- ing depression, anxiety, and Alzheimer's Disease (AD) and the use of probiotics as therapy for th- ese diseases remains promising. However, the mechanisms underlying the gut microenvironment's influence on disease pathogenesis and therapy remain unclear.
OBJECTIVE
The objective of this study is to investigate the effect of a novel probiotic formula, BIOCG, on cognitive function and pathobiological mechanisms, including amyloid processing and dendritic spine dynamics, in a mouse model of AD.
METHODS
BIOCG was administered for 3 months to 3xTg or 3xTg; Thy1-YFP AD mice and func- tional outcomes were assessed via behavioral testing and electrophysiology. Mechanisms relevant to AD pathogenesis including dendritic spine morphology and turnover, Amyloid Precursor Pro- tein (APP) processing and microglial phenotype were also evaluated. Finally, we sequenced fecal samples following probiotic treatment to assess the impact on gut microbial composition and corre- late the changes with the above described measures.
RESULTS
Mice treated with BIOCG demonstrated preserved cognitive abilities and stronger Long- Term Potentiation (LTP), spontaneous Excitatory Postsynaptic Currents (sEPSC), and glutamate-in- duced LTPs, indicative of functional and electrophysiological effects. Moreover, we observed atten- uated AD pathogenesis, including reduced Amyloid Beta (Aβ) burden, as well as more mature den- dritic spines in the BIOCG-treated. Our finding of changes in microglial number and phenotype in the treatment group suggests that this formulation may mediate its effects via attenuation of neu- roinflammation. Sequencing data confirmed that the gut microbiome in treated mice was more varied and harbored a greater proportion of "beneficial" bacteria.
CONCLUSION
Overall, our results indicate that treatment with BIOCG enhances microbial diversity and, through gut-brain axis interactions, attenuates neuroinflammation to produce histologic and functional improvement in AD pathogenesis.