期刊
JOURNAL OF ALZHEIMERS DISEASE
卷 60, 期 4, 页码 1241-1257出版社
IOS PRESS
DOI: 10.3233/JAD-170020
关键词
aging; Alzheimer's disease; gut microbiota; mouse model; short chain fatty acids
资金
- National Science Fund for Young Scholars [81500938]
- PUMC
- Fundamental Research Funds for the Central Universities [3332015151]
- CAMS Innovation Fund for Medical Sciences (CIFMS) [2016-I2M-1-010]
The topic of gut microbiota is currently attracting considerable interest as a potential factor in Alzheimer's disease (AD). However, the extent and time course of alterations in the gut microbiota, and their effects on AD pathology remain uncertain. Herein, we compared the fecal microbiomes and fecal short chain fatty acid composition (SCFAs) between wildtype and AD model mice at different ages under strictly controlled specific pathogen free conditions, and also conducted microscopic investigations of intestinal structures. Our results showed that the microbiota composition and diversity were perturbed and the level of SCFAs was reduced in AD mice, predicting alterations in more than 30 metabolic pathways, which may be associated with amyloid deposition and ultrastructural abnormalities in AD mouse intestine. These findings indicate that AD pathology might not only affect brain function directly, but also exacerbate cognitive deficits through reducing the level of SCFAs via alterations of gut microbiota induced by intestinal amyloid deposition. Our data may support a role of gut microbiota, and suggest a novel route for therapeutic intervention in AD.
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