Aerobic exercise regulates gut microbiota profiles and metabolite in the early stage of Alzheimer's disease.

Aerobic exercise (AE) has been shown to offer significant benefits for Alzheimer's disease (AD), potentially influencing the gut microbiota. However, the impact of changes in intestinal flora in early Alzheimer's disease induced by aerobic exercise on metabolic pathways and metabolites is not well understood. In this study, 3-month-old APP/PS1 and C57BL/6 mice were divided into two groups each: a control group (ADC for APP/PS1 and WTC for C57BL/6) and an aerobic exercise group (ADE for APP/PS1 and WTE for C57BL/6). The exercise groups underwent a 20-week aerobic training program on a motorized treadmill before the behavioral test (both the Morris water maze experiment (MWM) and the eight-arm maze test). Fecal samples were collected to analyze gut microbiota profiles via 16S rRNA gene sequencing. At the same time, the metabolic pathway analysis and the detection of metabolites were carried out. At the phylum level, the ADE group exhibited a significant reduced in the relative abundance of Bacteroidetes compared to the ADC group. At the genus level, both Ileibacterium and Faecalibaculum were found to be more abundant in the ADE group than in the ADC group. Additionally, PICRUSt analysis revealed that lipid metabolism and bile acid metabolism pathways were significantly enriched in the cecal microbiota of mice in the ADE group. The metabolites detected further confirmed the changes in the metabolic pathways mentioned above. Aerobic exercise may modify gut microbiota profiles and metabolites in APP/PS1 mice, thereby potentially playing a beneficial role in delaying cognitive impairment associated with early-stage Alzheimer's disease.