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

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. 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. 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. 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.