Integrative Metabolomic Characterization Reveals the Mediating Effect of Bifidobacterium breve on Amino Acid Metabolism in a Mouse Model of Alzheimer’s Disease

Abstract

Alzheimer’s disease (AD) is commonly accompanied by global alterations in metabolic profiles, resulting in cognitive impairment and neuroinflammation in the brain. Using ultraperfor-mance liquid chromatography-mass spectrometry, we performed integrative untargeted metabo-lomic analysis of metabolite alterations in the serum and hippocampal tissues of amyloid-β (Aβ)-injected AD model mice and sham controls. Multivariate analysis revealed that a Bifidobacterium breve CCFM1025 intervention significantly restored the differential metabolites induced by Aβ-in-jection, resulting in B. breve CCFM1025 serum and hippocampal metabolomes clustering between control and model mice. Furthermore, pathway and metabolite set enrichment analysis found that these altered metabolites were predominantly linked to amino acid metabolism. Overall, the integrative metabolome analysis indicated that B. breve CCFM1025 supplementation could modulate serum and hippocampal metabolomes in the early stage of AD, with amino acids as a potential driver.