期刊
BIOMED RESEARCH INTERNATIONAL
卷 2020, 期 -, 页码 -出版社
HINDAWI LTD
DOI: 10.1155/2020/8456596
关键词
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资金
- National Key R&D Program of China [2018YFE0203600]
- National Natural Science Foundation of China [31671047]
- Guangdong Provincial Key ST Program [2018B030336001]
- Guangdong Provincial Fund for Basic and Applied Basic Research [2019B1515130004, 19201910260000033]
- Shenzhen Knowledge Innovation Program [JCYJ20170413165053031, JCYJ20170413173717055]
- Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions [NYKFKT2019003]
- Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence Fund [2019001]
Emerging evidence suggests that the gut microbiome actively regulates cognitive functions and that gut microbiome imbalance is associated with Alzheimer's disease (AD), the most prevalent neurodegenerative disorder. However, the changes in gut microbiome composition in AD and their association with disease pathology, especially in the early stages, are unclear. Here, we compared the profiles of gut microbiota between APP/PS1 transgenic mice (an AD mouse model) and their wild-type littermates at different ages by amplicon-based sequencing of 16S ribosomal RNA genes. Microbiota composition started diverging between the APP/PS1 and wild-type mice at young ages (i.e., 1-3 months), before obvious amyloid deposition and plaque-localized microglial activation in the cerebral cortex in APP/PS1 mice. At later ages (i.e., 6 and 9 months), there were distinct changes in the abundance of inflammation-related bacterial taxa including Escherichia-Shigella, Desulfovibrio, Akkermansia, and Blautia in APP/PS1 mice. These findings suggest that gut microbiota alterations precede the development of key pathological features of AD, including amyloidosis and plaque-localized neuroinflammation. Thus, the investigation of gut microbiota might provide new avenues for developing diagnostic biomarkers and therapeutic targets for AD.
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