Gut Microbial Metabolites in Alzheimer's Disease: From Disease Mechanisms to Therapeutic Opportunities—A Narrative Review (2021–2026)

Alzheimer's disease is a progressive brain disorder that affects memory, thinking, and daily life. While amyloid plaques and tau tangles are well-known markers of the disease, recent research shows that the gut microbiome—specifically the chemical signals or "metabolites" produced by gut bacteria—plays a crucial role in how Alzheimer's develops and progresses. This narrative review summarizes key research published between 2021 and 2026 to explore how gut microbial metabolites influence Alzheimer’s disease and what this means for future treatments. Through the gut-brain axis, metabolites such as short-chain fatty acids (SCFAs), bile acids, tryptophan derivatives (like indole-3-propionic acid), and trimethylamine N-oxide (TMAO) interact with the brain. They can either protect the brain or worsen damage by influencing inflammation, oxidative stress, and the strength of the blood-brain barrier. We also examine emerging perspectives, including how oral bacteria (the oral-gut-brain axis) and biological sex differences shape these gut-brain interactions. In addition, we evaluate potential treatments like dietary changes, prebiotics, probiotics, and fecal microbiota transplantation (FMT). While preclinical animal studies show promising results, human clinical evidence remains limited and inconsistent. Well-designed clinical trials and multi-omics approaches are still needed to turn these insights into effective, personalized therapies for Alzheimer's disease.