Selenium Intervention in Alzheimer's Disease Mice and Its Possible Involvement of the Gut-Brain Axis

Alzheimer's disease (AD) is a neurodegenerative disease closely associated with alterations in the gut microbiota (GM). The impact on GM may be one of the mechanisms by which selenium (Se) prevents and treats AD. This study investigated the effects of sodium selenite interventions on GM-driven metabolic changes and microbiome-gut-brain axis (MGBA) communication in triple transgenic AD mice (3×Tg-AD) using 16S rDNA sequencing and metabolomics. The results demonstrated that Se intervention significantly altered the GM of AD mice, with notable enhancement in pathways related to amino acid metabolism (tyrosine and phenylalanine metabolism, tryptophan metabolism) and lipid metabolism (glycerol degradation). Metabolomics analysis identified 119 differentially expressed metabolites (DEMs) in gut contents, 42 in serum, and 63 in the cortex, which were involved in metabolic pathways such as arachidonic acid metabolism, bile acid biosynthesis, and phospholipid biosynthesis. Correlation analysis revealed that Family_XIII_AD3011_group and Alistipes, identified as key microbiotas, were significantly associated with multiple DEMs in peripheral to central brain tissue. Moreover, lipid metabolites exhibited close relationships with various tissues. These findings indicate that Se intervention increases the abundance of certain beneficial bacteria while suppressing harmful ones in the gut and affecting metabolic pathways, thereby improving cognitive function and pathological features in 3×Tg-AD mice.