Fecal 16S rRNA sequencing and multi-compartment metabolomics revealed gut microbiota and metabolites interactions in APP/PS1 mice.

BACKGROUND:Alzheimer's disease is a significant public health issue. Recent studies have shown that the gut microbiota plays a vital role in the onset and development of Alzheimer's disease. However, the potential role of the gut microbiota and the associated metabolic characteristics require further elucidation. METHODS:The gut microbial compositions of APP/PS1 mice were analyzed using 16S rRNA gene sequencing. Metabolomics was used to characterize changes in metabolic profiles in feces, serum, and cortex. A multi-omics approach investigated the potential associations between gut microbes and metabolites. RESULTS:The gut microbiota composition was markedly different between APP/PS1 mice and normal mice. Metabolomic analysis identified 253 fecal metabolites, 16 serum metabolites, and 123 cortical metabolites that were differentially abundant in APP/PS1 that may be potential biomarkers of AD. Nearly half of these metabolites were lipids. A combined analysis of the three sample types showed a correlation between fecal fatty acids and glycerolipids, serum glycerophospholipids, and cortical fatty acids. Furthermore, our study showed that Marinifilaceae and Akkermansiaceae were closely related to these lipids and lipid-like molecules, particularly fatty acids and glycerophospholipids. CONCLUSION:Our study highlighted the interactions between the gut microbiome and the fecal, serum, and cortical metabolomes. This interaction provides a new direction for further exploring the link between gut microbiota composition and metabolism in Alzheimer's disease.