• KSBNS 2024


Original Article

Exp Neurobiol 2017; 26(6): 369-379

Published online December 31, 2017

© The Korean Society for Brain and Neural Sciences

Metagenome Analysis of Bodily Microbiota in a Mouse Model of Alzheimer Disease Using Bacteria-derived Membrane Vesicles in Blood

Jin-Young Park1, Juli Choi1, Yunjin Lee1, Jung-Eun Lee1, Eun-Hwa Lee1, Hye-Jin Kwon1, Jinho Yang2, Bo-Ri Jeong2, Yoon-Keun Kim2 and Pyung-Lim Han1,3*

1Department of Brain and Cognitive Sciences, Ewha Womans University, Seoul 03760, 2MD Healthcare Inc., Seoul 03923, 3Department of Chemistry and Nano Science, Ewha Womans University, Seoul 03760, Korea

Correspondence to: *To whom correspondence should be addressed.
TEL: 82-2-3277-4130, FAX: 82-2-3277-3419

Received: July 26, 2017; Revised: October 23, 2017; Accepted: December 1, 2017

Emerging evidence has suggested that the gut microbiota contribute to brain dysfunction, including pathological symptoms of Alzheimer disease (AD). Microbiota secrete membrane vesicles, also called extracellular vesicles (EVs), which contain bacterial genomic DNA fragments and other molecules and are distributed throughout the host body, including blood. In the present study, we investigated whether bacteria-derived EVs in blood are useful for metagenome analysis in an AD mouse model. Sequence readings of variable regions of 16S rRNA genes prepared from blood EVs in Tg-APP/PS1 mice allowed us to identify over 3,200 operational taxonomic units corresponding to gut microbiota reported in previous studies. Further analysis revealed a distinctive microbiota landscape in Tg-APP/PS1 mice, with a dramatic alteration in specific microbiota at all taxonomy levels examined. Specifically, at the phylum level, the occupancy of p_Firmicutes increased, while the occupancy of p_Proteobacteria and p_Bacteroidetes moderately decreased in Tg-APP/PS1 mice. At the genus level, the occupancy of g_Aerococcus, g_Jeotgalicoccus, g_Blautia, g_Pseudomonas and unclassified members of f_Clostridiale and f_Ruminococcaceae increased, while the occupancy of g_Lactobacillus, unclassified members of f_S24-7, and g_Corynebacterium decreased in Tg-APP/PS1 mice. A number of genus members were detected in Tg-APP/PS1 mice, but not in wild-type mice, while other genus members were detected in wild-type mice, but lost in Tg-APP/PS1 mice. The results of the present study suggest that the bodily microbiota profile is altered in Tg-APP/PS1 mice, and that blood EVs are useful for the metagenome analysis of bodily microbiota in AD.

Graphical Abstract

Keywords: Alzheimer Disease, Microbiota, Metagenomics