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J Alzheimers Dis. 2017;60(4):1241-1257. doi: 10.3233/JAD-170020.

Altered Gut Microbiota in a Mouse Model of Alzheimer's Disease.

Zhang L1,2, Wang Y1,2, Xiayu X1,2, Shi C1,2, Chen W1,2, Song N1,2, Fu X1,2, Zhou R1,2, Xu YF1,2, Huang L1,2, Zhu H1,2, Han Y1,2, Qin C1,2.

Author information

1
Key Laboratory of Human Diseases Comparative Medicine, Ministry of Health, Institute of Medical Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS), Beijing, China.
2
Key Laboratory of Human Diseases Animal Models, State Administration of Traditional Chinese Medicine, Peking Union Medicine College (PUMC), Beijing, China.

Abstract

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 wild-type 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.

KEYWORDS:

Alzheimer’s disease; aging; gut microbiota; mouse model; short chain fatty acids

PMID:
29036812
DOI:
10.3233/JAD-170020
[Indexed for MEDLINE]

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