Gut Microbiome Alterations Precede Cerebral Amyloidosis and Microglial Pathology in a Mouse Model of Alzheimer’s Disease

• Published in: BioMed research international 2020, Vol.2020 (2020), p.1-15
• Main Authors: Ma, Yingfei, Chen, Yu, Chen, Yuewen, Li, Jing, Lin, Li, Fan, Yingying, Zhou, Haokui, Chen, Shuo, Fang, Lihua, Chen, Yijing, Xu, Jinying
• Format: Article
• Language: English
• Subjects: Advertising executives; Age; Age Factors; Alzheimer Disease - genetics; Alzheimer Disease - pathology; Alzheimer's disease; Amyloidosis; Amyloidosis - genetics; Amyloidosis - pathology; Animals; Bacteria; Biomarkers; Biomedical research; Brain; Brain - pathology; Brain Diseases - genetics; Brain Diseases - pathology; Cerebral cortex; Cerebrum; Cognitive ability; Comparative analysis; Composition; Cytokines; Deoxyribonucleic acid; Diagnostic systems; Digestive system; Disease Models, Animal; DNA; Feces; Gastrointestinal Microbiome - genetics; Gene sequencing; Genetic engineering; Inflammation; Inflammation - pathology; Intestinal microflora; Male; Mice; Mice, Transgenic; Microbiomes; Microbiota; Microbiota (Symbiotic organisms); Microglia - pathology; Nervous system; Neurodegenerative diseases; Pathology; Phylogenetics; Presenilin 1; Ribosomal RNA; rRNA 16S; Software; Target marketing; Taxonomy; Therapeutic applications; Transgenic mice
• ISSN: 2314-6133; 2314-6141
• DOI: 10.1155/2020/8456596

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.