Microbial Metabolomes in Alzheimer's Disease: From Pathogenesis to Therapeutic Potential.

Background: Accumulating evidence underscores the potential role of the gut microbiome in the pathogenesis of Alzheimer's disease, but much remains to be clarified. This review examines current evidence linking gut microbiome dysbiosis to Alzheimer's disease, focusing on microbial metabolomes and their mechanistic role, as well as on the potential of therapeutic approaches targeting the gut microbiome.

Methods: A narrative, non-systematic examination of the literature was conducted to provide a comprehensive overview of the subject under examination. Database searches were performed in PubMed, Scopus, and Web of Science between June and July 2025.

Results: Alzheimer's disease is linked to reduced gut microbial diversity and altered bacterial taxa. Gut microbiome shifts correlate with inflammation and may drive Alzheimer's disease progression via the microbiota-gut-brain axis. Microbial amyloids and bacterial products can cross both the intestinal and blood-brain barrier, triggering neuroinflammation and promoting amyloid and tau pathologies. Short-chain fatty acids produced by the gut microbiome regulate neuroinflammation, lipid metabolism, and gene expression, impacting Alzheimer's disease pathology. Therapeutics targeting the gut microbiome, including probiotics, prebiotics, and fecal microbiota transplantation, show promise in modulating neuroinflammation, reducing amyloid and tau pathology, and improving cognitive function in Alzheimer's disease.

Conclusions: The gut microbiome significantly influences Alzheimer's disease pathogenesis, and its modulation offers potential to slow progression. However, further research is required to validate effective clinical interventions.