Gut microbiome synthesizes important core metabolites to prevent cognitive decline and mitigate onset and progression of Alzheimer's disease.

Background: This study explores how gut metabolites, produced through bacterial metabolism in the gut, influence neurological conditions like Alzheimer's disease (AD). Key metabolites such as succinate and short-chain fatty acids signal through the autonomic nervous system and can cross the blood-brain barrier, impacting central nervous system functions. Objective: The aim is to examine the role of the gut microbiota in compensating for metabolic deficiencies in AD. By analyzing wild-type (WT) and APP/PS1 mice, the study investigates how the microbiome affects key metabolic processes and whether it can slow AD progression. Methods: High-throughput sequencing data from the gut microbiomes of APP/PS1 transgenic AD model mice and age-matched WT C57BL/6 male mice were analyzed for microbial and metabolite profiles. Results: Alpha and beta diversity analyses showed differences in microbial composition between groups. Partial least squares discriminant analysis and Anosim confirmed distinct microbiome profiles in WT and APP/PS1 mice. At the genus level, Conclusions: While taxonomic differences did not directly link specific microorganisms to AD, functional analysis identified key metabolites-acetyl-CoA, glucose, succinate, lipids, choline, and acetylcholine-that may alleviate energy deficits and synaptic dysfunction. This study suggests that the microbiome may help compensate for AD-related impairments, opening avenues for microbiome-based therapies.