Microbiome alterations in Alzheimer's disease: A systematic review of current evidence and global perspectives.

Abstract

<h4>Background</h4>Growing evidence implicates the gut-brain axis in Alzheimer's disease (AD), with gut microbiome dysbiosis proposed to modulate neuroinflammation, amyloid pathology, and cognitive decline.<h4>Objective</h4>To systematically synthesize human studies (2021-2025) profiling gut microbiomes in AD; identify consistent taxonomic and functional signatures; map geographic study distribution; and highlight translational gaps.<h4>Methods</h4>A PRISMA-compliant systematic review of human studies using 16S rRNA, metagenomics, metatranscriptomics, or fecal microbiota transplantation (FMT)/probiotic designs was conducted. Two reviewers screened studies and assessed quality using Joanna Briggs Institute tools. Owing to heterogeneity, findings were narratively synthesized across microbiome diversity, taxonomy, function, metabolism, oral-brain links, causality, interventions, and predictive analyses.<h4>Results</h4>Thirty-seven studies, mainly from Asia with some from Europe, North America, and Africa, revealed consistent gut dysbiosis in AD. Findings show reduced alpha-diversity, loss of short-chain fatty acid-producing bacteria (e.g., <i>Faecalibacterium prausnitzii</i>, <i>Bifidobacterium</i>), and enrichment of pro-inflammatory taxa (<i>Escherichia/Shigella</i>, <i>Proteobacteria</i>). Functional analyses indicate reduced butyrate synthesis, disrupted lipid and tryptophan-kynurenine metabolism, and links with apolipoprotein epsilon (ε4) gene and cognition. Limited causal evidence arises from Mendelian randomization and small FMT trials, with randomized, longitudinal confirmation still needed.<h4>Conclusions</h4>Current evidence suggests a biologically plausible association between gut microbiota and AD pathogenesis, positioning microbiome-derived biomarkers and interventions as promising but still exploratory avenues. Harmonized, longitudinal, multi-omic, and geographically inclusive studies are urgently needed to clarify causal mechanisms and translate these correlational findings into validated diagnostics and therapeutics.