Gut microbiota regulate cognitive deficits and amyloid deposition in a model of Alzheimer's disease.

Abstract

Gut microbiota, comprising a vast number of microorganism species with complex metagenome, are known to be associated with Alzheimer's disease (AD) and amyloid deposition. However, studies related to gut microbiota have been mostly restricted to comparisons of amyloid deposits, while investigations on neurobehavioral changes and the pathogenesis of AD are limited. Therefore, we aimed to identify the relationship between changes in the intestinal microbiome and the pathogenesis of AD. APPswe /PS1ΔE9 (PAP) transgenic mice and wild-type (WT) mice of different age groups were used. The composition of intestinal bacterial communities in the mice was determined by 16S ribosomal RNA sequencing (16S rRNA Seq), and the Y maze was used to measure cognitive function. Transcriptome sequencing (RNA Seq) and Gene Expression Omnibus (GEO) database (GSE 36980) were used to filter differentially expressed genes (DEGs) between specific pathogen-free (SPF) and germ-free (GF) mice. Quantitative reverse-transcriptase PCR (qRT-PCR) and western blot (WB) were used to verify the results. We found that the intestinal microbiota was significantly different between 5-month-old PAP and WT mice and the cognition of SPF PAP mice was diminished compared to GF PAP and SPF WT mice. DEGs in 5-month-old SPF and GF mice were enriched in the MAPK signalling pathway, and expression of amyloid precursor protein and amyloid deposition increased in 5-month-old SPF PAP mice. Results from this study showed that changes in intestinal microbiota were correlated with impairment of cognitive function and might promote amyloid deposition by stimulating the MAPK signalling pathway in the brain.