Abstract
Although an intriguing potential association of the gut microbiome with Alzheimer's disease (AD) has attracted recent interest, few studies have directly assessed this relationship or underlying mechanism. Here, we compared the gut microbiota composition and functional differentiation of senescence-accelerated mouse prone 8 (SAMP8) mice with control senescence-accelerated mouse resistant 1 (SAMR1) mice using 16S rRNA gene and metagenomic sequencing analysis, respectively. Specifically, 16S sequencing results showed that the SAMP8 mice displayed a characteristic composition of the gut microbiome that clearly differed from that of the SAMR1 mice. Moreover, network analysis revealed that the gut microbiota of SAMP8 mice had decreased correlation density and clustering of operational taxonomic units. Metagenomic results revealed that the predominant Cluster of Orthologous Groups functional category related to these changes was the metabolism cluster in SAMP8 mice. The Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation further demonstrated enrichment of the relative abundance of some dominant metabolism-related KEGG pathways in the SAMP8 mice, consistent with the suggested pathogenic mechanisms of AD. In conclusion, this study suggests that perturbations of the gut microbiota composition and the functional metagenome may be associated with AD. Further studies are warranted to elucidate the potential new mechanism contributing to AD progression.
Highlights
Alzheimer’s disease (AD) is a neurodegenerative disease, characterized by the progressive development of cognitive impairment, representing one of the greatest health challenges worldwide [1]
The senescence-accelerated mouse prone 8 (SAMP8) mice randomly swam in the tank without knowing the target location, whereas the senescence-accelerated mouse resistant 1 (SAMR1) mice preferentially searched for the target quadrant (Fig. 1B)
The relative abundance of Prevotella and Bacteroides was increased, while the abundances of unclassified_f__Lachnospiraceae, Clostridium, and Blautia decreased in SAMP8 compared to SAMR1 mice. This is the first examination of specific patterns of gut microbiota composition and function in a transgenic mouse model of Alzheimer's disease (AD) using both 16S rRNA gene and metagenomics sequencing of fecal samples
Summary
Alzheimer’s disease (AD) is a neurodegenerative disease, characterized by the progressive development of cognitive impairment, representing one of the greatest health challenges worldwide [1]. Alteration of the gut microbiome was observed in AD transgenic mice [1317], AD patients [18, 19], and transgenic AD Drosophila [20]. All of these previous studies were based on a 16S rRNA gene sequencing method to determine the microbiota composition, which has known limitations such as the potential for skewing the results owing to amplification bias [21] and inability to identify most microbes at the species and strain level [22]. No study has yet conducted metagenome sequencing analysis of the gut microbiome in relation to AD
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