Review Article · Volume 12, Issue 4 · December 2025
1 Institute of Neuroscience, University of Barcelona, Spain
2 Department of Microbiology, Karolinska Institute, Stockholm, Sweden
3 Centre for Microbiome Research, University of Ghana, Accra, Ghana
Growing evidence implicates the gut-brain axis in the pathogenesis of neurodegenerative diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD). The gut microbiome produces metabolites and neuroactive compounds that may influence neuroinflammation, protein aggregation, and synaptic function. However, disease-specific microbial signatures remain poorly characterized across diverse populations.
We conducted a comprehensive review and meta-analysis of 47 studies (n=8,340 participants) examining gut microbiome composition in patients with AD, PD, amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD). We analyzed 16S rRNA and shotgun metagenomic data using standardized bioinformatic pipelines and assessed functional metabolic pathways associated with disease states.
Consistent alterations in gut microbial composition were identified across neurodegenerative conditions. Patients with AD showed decreased Faecalibacterium and Roseburia abundance (effect size: −0.72, 95% CI: −0.91 to −0.53), while PD patients exhibited enrichment of Akkermansia and depletion of Prevotella. Functional analysis revealed shared disruption of short-chain fatty acid production and tryptophan metabolism pathways across all four diseases. Geographic and dietary confounders accounted for approximately 15% of observed variance.
Our meta-analysis identifies convergent and disease-specific microbiome signatures in neurodegeneration, highlighting shared metabolic disruptions that may represent therapeutic targets. These findings support the development of microbiome-based diagnostics and interventions, though standardized protocols and longitudinal studies are needed to establish causality.