Gut metagenomics-derived genes as potential biomarkers of Parkinson’s disease Original paper

What was studied?

Gut microbial gene markers for Parkinson’s disease were investigated in this original case–control metagenomic study using stool-derived DNA to develop and validate a microbial gene-based diagnostic index. The study specifically targeted gut microbiome genes, metagenomic species and functional pathways that differentiate Parkinson’s disease from controls and related neurodegenerative disorders, aiming for clinically deployable biomarkers.

Who was studied?

The discovery cohort comprised 40 idiopathic Parkinson’s disease patients and their healthy spouses, all Han Chinese, living together for at least 20 years to minimise dietary and environmental confounding. Strict exclusion criteria removed atypical Parkinsonism, systemic illnesses, gastrointestinal disease, metabolic and autoimmune conditions, recent antibiotics, and probiotic use. An independent test cohort included 78 Parkinson’s disease patients, 75 unrelated healthy controls, 40 multiple system atrophy (MSA) patients, and 25 Alzheimer’s disease patients, enabling assessment of diagnostic performance and disease specificity across movement and non-movement neurodegenerative disorders.

Most important findings

Shotgun metagenomics of 40 case–spouse pairs generated a catalogue of over 1.1 million gut microbial genes with altered alpha and beta diversity in Parkinson’s disease, and two enterotypes dominated by Bacteroides or Prevotella that were not disease-specific, as illustrated in the diversity and enterotype plots on page 7. Genes differing between groups (≈175,000) were clustered into 153 metagenomic species (MGS); Parkinson’s disease showed enrichment of MGS related to Alistipes and Akkermansia muciniphila and depletion of multiple Bacteroides-linked MGS, particularly Bacteroides coprocola, visualised in the heatmap and co-occurrence network on page 9.awaa201 At taxonomic level, Parkinson’s disease stools were enriched for Archaea, Synergistetes, Verrucomicrobia, and certain Firmicutes species; Streptococcus salivarius abundance correlated negatively with levodopa equivalent dose, while Enterobacter cloacae correlated positively with UPDRS total score, hinting at drug–microbe and microbe–severity relationships.awaa201 Using minimum redundancy–maximum relevance feature selection on 51,816 Parkinson’s associated genes, the authors derived 25 optimal gut microbial gene markers and built a support vector machine–based Parkinson’s disease index (PDI). In the metagenomic dataset, this achieved an AUC of 0.896; importantly, PERMANOVA showed PDI was unaffected by age, BMI, lifestyle, constipation or dopaminergic medications. Real-time PCR assays targeting the same 25 genes reproduced performance in the discovery couples (AUC 0.922) and in the independent cohort (AUC 0.905 vs healthy controls; 0.831 vs MSA; 0.901 vs Alzheimer’s disease). Ten of the 23 annotated markers mapped to Bacteroides, seven specifically to B. coprocola, while one mapped to a hypothetical protein of A. muciniphila, underscoring a gene-level signature that refines and stabilises previously inconsistent taxonomic findings.

Key implications

Clinically, this work proposes a faecal, gene-based microbiome index that discriminates Parkinson’s disease from ageing controls and from MSA and Alzheimer’s disease, independent of motor severity or dopaminergic therapy. For microbiome-signature databases, it supplies a 25-gene panel linked to specific taxa (notably Bacteroides coprocola and Akkermansia muciniphila), enriched viral and archaeal signals, and associated functional shifts in amino acid, vitamin, and energy metabolism. Together, these features offer a translatable bridge between discovery metagenomics and scalable real-time PCR assays suitable for routine neurology practice and longitudinal risk stratification.

Citation

Qian Y, Yang X, Xu S, et al. Gut metagenomics-derived genes as potential biomarkers of Parkinson’s disease. Brain. 2020;143(8):2474-2489. doi:10.1093/brain/awaa201