Gut Microbial Metabolites in Alzheimer’s Disease: A Liver-Centered Perspective on the Gut–Liver–Brain Axis

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by β-amyloid deposition and tau hyperphosphorylation. Multiple communication pathways link the central nervous system (CNS), liver, and gut microbiota, collectively forming the gut–liver–brain axis, in which the liver serves as a metabolic and immune hub. Emerging evidence suggests that this axis may be involved in AD pathogenesis. Among gut microbiota-associated metabolites, short-chain fatty acids (SCFAs), bile acids (BAs), and trimethylamine N-oxide (TMAO) have been linked to AD pathology and may modulate metabolic and inflammatory pathways involved in pathogenesis. This review summarizes current evidence on their roles in AD progression within the gut–liver–brain axis, with particular emphasis on hepatic metabolism and hepatic immune regulation within this axis. It also discusses hepatic and neuronal autophagy as potential links between metabolic disturbances, mitochondrial dysfunction, and AD pathology. Finally, the potential of targeting different components of this axis is discussed as a direction for future therapeutic research.