小鼠的阿尔茨海默病进程可通过调节肠道菌群控制

Title：
Microbiota modulation counteracts Alzheimer's disease progression influencing neuronal proteolysis and gut hormones plasma levels

DOI：
10.1038/s41598-017-02587-2

Abstract：
Gut microbiota has a proven role in regulating multiple neuro-chemical pathways through the highly interconnected gut-brain axis. Oral bacteriotherapy thus has potential in the treatment of central nervous system-related pathologies, such as Alzheimer's disease (AD). Current AD treatments aim to prevent onset, delay progression and ameliorate symptoms. In this work, 3xTg-AD mice in the early stage of AD were treated with SLAB51 probiotic formulation, thereby affecting the composition of gut microbiota and its metabolites. This influenced plasma concentration of inflammatory cytokines and key metabolic hormones considered therapeutic targets in neurodegeneration. Treated mice showed partial restoration of two impaired neuronal proteolytic pathways (the ubiquitin proteasome system and autophagy). Their cognitive decline was decreased compared with controls, due to a reduction in brain damage and reduced accumulation of amyloid beta aggregates. Collectively, our results clearly prove that modulation of the microbiota induces positive effects on neuronal pathways that are able to slow down the progression of Alzheimer's disease.

All Authors：
Laura Bonfili,Valentina Cecarini,Sara Berardi,Silvia Scarpona,Jan S Suchodolski,Cinzia Nasuti,Dennis Fiorini,Maria Chiara Boarelli,Giacomo Rossi,Anna Maria Eleuteri

First Authors：
Laura Bonfili

Correspondence：
Laura Bonfili

内容要点：

实验采用3xTg-AD转基因小鼠和野生型小鼠（wt），各分两组：一组给予乳酸菌和双歧杆菌制剂（SLAB51），另一组为对照，数周后进行行为学、生化指标等分析。结果显示3xTg-AD和wt小鼠菌群存在显著差异，SLAB51组菌群组成及与能量、氨基酸和核苷酸相关的代谢发生改变，双歧杆菌增加，弯曲菌目减少，血浆炎症因子水平降低，胃肠激素水平升高。与此同时， SLAB51修复泛素蛋白水解酶体通路及自噬系统，减少Aβ蛋白的积累，提高认知功能。