Gut microbiota dysbiosis in Parkinson disease: A systematic review and pooled analysis Original paper

What was reviewed?

This systematic review and pooled re-analysis examined gut microbiota dysbiosis in Parkinson’s disease, focusing on how gut microbiota dysbiosis in Parkinson’s disease emerges when raw sequencing data are reprocessed through a single, harmonized bioinformatic and statistical pipeline. The authors systematically identified human case–control studies comparing fecal microbiota in Parkinson’s disease (PD) versus non-PD controls, then re-downloaded raw 16S rRNA gene sequencing data (or least-processed data) and reanalyzed them using a unified workflow. Key steps included trimming all studies to the V4 region, processing reads with DADA2, standardized quality filtering, and uniform taxonomic assignment. Bayesian mixed models were then applied to alpha diversity, beta diversity, and taxon-level abundance, with confirmatory analyses using ANCOM-BC in a two-stage meta-analysis. The core aim was to strip away methodological noise (different variable regions, pipelines, statistics) and reveal which microbial signatures are robustly associated with PD across studies.

Who was reviewed?

The pooled dataset comprised nine human studies, with 1843 total participants: 1092 individuals with PD and 751 non-PD controls from six countries (including Italy, USA, Finland, Germany, and China). Sample sizes per study ranged from 59 to 507 participants, and most studies used some form of matching (age, sex, BMI, geography, or spouses) to select controls, aiming to control lifestyle and demographic confounders (Table 1, page 4). All studies used Illumina MiSeq 16S rRNA sequencing, targeting V3–V5 regions, though the original analyses varied in pipelines (QIIME, mothur, DADA2) and statistical methods. After strict filtering (including removal of low-depth samples), 258 observations were excluded, largely from a single low-coverage dataset. Overall, the population is representative of typical PD cohorts: mostly older adults, on dopaminergic therapy, with varying disease duration and severity; a subset of studies provided detailed medication and Hoehn & Yahr staging, enabling exploration of medication and progression effects on microbial taxa.

Most important findings

Harmonization largely erased the dramatic between-study differences in alpha diversity previously reported.

Key implications

For clinicians and translational researchers, the review supports a focused model: gut microbiota dysbiosis in Parkinson disease is characterized less by global diversity loss and more by selective depletion of butyrate-producing commensals (Faecalibacterium, Roseburia, Lachnospiraceae) plus enrichment of mucus-degrading Akkermansia and several low-abundance taxa linked to inflammation and barrier disruption. Reduced short-chain fatty acid (SCFA) production and thinning of the mucus layer may increase intestinal permeability, facilitating translocation of inflammatory metabolites and potentially α-synuclein-inducing signals to the enteric nervous system and, via the vagus nerve or systemic circulation, to the brain. This mechanistic framing aligns with elevated fecal and serum markers of gut inflammation and permeability in PD and provides concrete microbial candidates for a signatures database. However, nearly all included studies were cross-sectional and conducted in treated patients, so causality and medication effects remain unresolved; longitudinal work in treatment-naïve cohorts is crucial before deploying these taxa as predictive biomarkers or therapeutic targets.

Citation

Kleine Bardenhorst S, Cereda E, Severgnini M, et al. Gut microbiota dysbiosis in Parkinson’s disease: A systematic review and pooled analysis. Eur J Neurol. 2023;30(11):3581-3594. doi:10.1111/ene.15671