Comparisons of metabolites and gut microbiota profiles for both young and middle-aged APPSwe/PS1De9 mice

• Published in: Neuroscience Vol. 577; pp. 54 - 63
• Main Authors: Wang, Guiping, Ma, Tongtong, Liu, Ruitong, Gu, Huiwen, Zhou, Zheng-Yu, Wan, Zhongxiao
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 21.06.2025
• Subjects: Aging; Aging - metabolism; Alzheimer Disease - metabolism; Alzheimer Disease - microbiology; Alzheimer’s disease; Amyloid beta-Protein Precursor - genetics; Amyloid beta-Protein Precursor - metabolism; Animals; Cerebral Cortex - metabolism; Disease Models, Animal; Female; Gastrointestinal Microbiome - physiology; Gut microbiota; Male; Metabolomics; Mice; Mice, Transgenic; Presenilin-1 - genetics; Gut microbiota; Aging; Metabolomics; Alzheimer’s disease
• ISSN: 0306-4522; 1873-7544; 1873-7544
• DOI: 10.1016/j.neuroscience.2025.04.053

•Different gut microbiota and metabolites profiles were observed in APP/PS1 mice at the ages of 6 months and 10 months.•Bacteroidetes was declined, Actinobacteria and TM7 bacteria were increased at aged mice compared to young mice.•Serum L-Leucine, thymine, and glucosamine 6-phosphate were lower at aged mice compared to young mice.•Serum sorbitol and palmitic acid were higher at aged mice compared to young mice. The research focused on exploring the differences and relationships between gut microbiota and metabolites at various stages of Alzheimer’s disease (AD), specifically using APP/PS1 mice at the ages of 6 months and 10 months. To assess metabolites in serum and cortex, and to evaluate gut microbiota profiles in cecal content, UPLC-MS/MS and 16S rRNA sequencing techniques were utilized, respectively. Findings indicated that, in comparison to younger mice, serum concentrations of L-Leucine, thymine, and Glucosamine 6-phosphate were lower, whereas levels of Sorbitol and Palmitic acid were higher. Furthermore, measurements of the ACE and Chao1 indices significantly declined in the older cohort. At the phylum level, the relative abundance of Bacteroidetes showed a decline, while there was an increase in Actinobacteria and TM7 bacteria among the middle-aged subjects. The novelty of this study is we found there were notable alterations in both gut microbiota and metabolites within serum and cortex when comparing young and older APP/PS1 mice, emphasizing the important connections between metabolites and gut microbiota throughout the progression of AD. These results indicate that manipulating metabolites and gut flora may serve as a vital strategy for the prevention and management of AD.