Reduction of Abeta amyloid pathology in APPPS1 transgenic mice in the absence of gut microbiota.
Reduction of Abeta amyloid pathology in APPPS1 transgenic mice in the absence of gut microbiota.
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DOI：
10.1038/srep41802
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发表时间：
2017-02-08
影响因子：
4.6
通讯作者：
Bolmont T
中科院分区：
文献类型：
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作者：
Harach T;Marungruang N;Duthilleul N;Cheatham V;Mc Coy KD;Frisoni G;Neher JJ;Fåk F;Jucker M;Lasser T;Bolmont T
阿尔茨海默氏病是西方世界最常见的痴呆症，但这种毁灭性的神经退行性疾病目前还没有治愈方法。尽管临床和实验证据表明肠道微生物群与许多脑部疾病有关，但其对阿尔茨海默病的影响尚不清楚。为此，我们对Aβ前体蛋白（APP）转基因小鼠模型粪便样本中的细菌16S rRNA进行了测序，发现与非转基因野生型小鼠相比，肠道微生物群发生了显著变化。随后，我们产生了无菌APP转基因小鼠，并发现与肠道微生物群对照小鼠相比，大脑Aβ淀粉样蛋白病理学急剧减少。重要的是，用来自常规饲养的APP转基因小鼠的微生物群定植无菌APP转基因小鼠增加了脑Aβ病理学，而用来自野生型小鼠的微生物群定植在增加脑Aβ水平方面效果较差。我们的研究结果表明微生物参与了A β淀粉样蛋白病理学的发展，并表明微生物群可能有助于神经退行性疾病的发展。
Alzheimer’s disease is the most common form of dementia in the western world, however there is no cure available for this devastating neurodegenerative disorder. Despite clinical and experimental evidence implicating the intestinal microbiota in a number of brain disorders, its impact on Alzheimer’s disease is not known. To this end we sequenced bacterial 16S rRNA from fecal samples of Aβ precursor protein (APP) transgenic mouse model and found a remarkable shift in the gut microbiota as compared to non-transgenic wild-type mice. Subsequently we generated germ-free APP transgenic mice and found a drastic reduction of cerebral Aβ amyloid pathology when compared to control mice with intestinal microbiota. Importantly, colonization of germ-free APP transgenic mice with microbiota from conventionally-raised APP transgenic mice increased cerebral Aβ pathology, while colonization with microbiota from wild-type mice was less effective in increasing cerebral Aβ levels. Our results indicate a microbial involvement in the development of Abeta amyloid pathology, and suggest that microbiota may contribute to the development of neurodegenerative diseases.