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

Apr 3, 2026Journal of Alzheimer's disease reports

Changes in gut bacteria linked to Alzheimer's disease: A review of current global research

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Abstract

Thirty-seven studies indicate consistent in Alzheimer's disease (AD).

Reduced alpha-diversity and loss of short-chain fatty acid-producing bacteria are observed in individuals with AD.
Enrichment of pro-inflammatory gut bacteria is associated with the disease.
Functional analyses demonstrate reduced butyrate production and disrupted metabolism of lipids and tryptophan.
Links with the apolipoprotein epsilon (ε4) gene and cognitive function are noted.
Causal evidence is limited, with some findings from Mendelian randomization and small fecal microbiota transplantation trials.

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BACKGROUND: 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.

OBJECTIVE: 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.

METHODS: 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.

RESULTS: Thirty-seven studies, mainly from Asia with some from Europe, North America, and Africa, revealed consistent in AD. Findings show reduced alpha-diversity, loss of short-chain fatty acid-producing bacteria (e.g.,,), and enrichment of pro-inflammatory taxa (,). 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. Faecalibacterium prausnitzii Bifidobacterium Escherichia/Shigella Proteobacteria

CONCLUSIONS: 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.

Key numbers

Study Count

Number of studies included in the systematic review.

131–152 million

Projected AD Cases

Projected global cases of Alzheimer's disease by 2050.

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

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