Parkinson’s Disease and the Gut Microbiome in Rural California Original paper

What was studied?

This original research article investigated the association between the gut microbiome and Parkinson’s disease (PD), focusing on both overall differences in microbial diversity/composition and the relationship between specific microbial taxa and clinical features of PD. The study utilized a community-based case-control design in rural California, analyzing fecal samples from PD patients and controls using 16S rRNA gene sequencing. The primary goals were to examine differences in gut microbiome diversity (alpha and beta diversity), relative abundance of microbial taxa, and predicted microbial functional pathways (metagenome) between PD patients and controls. Additionally, the study sought to determine whether particular microbiome signatures correlated with PD clinical characteristics such as disease duration, motor subtypes, L-DOPA dosage, and motor function severity (as measured by the Unified Parkinson’s Disease Rating Scale, UPDRS).

Who was studied?

The study enrolled 170 participants: 96 patients with Parkinson’s disease and 74 controls. Participants were recruited from three rural California counties (Kern, Tulare, and Fresno) as part of the Parkinson’s, Environment and Gene (PEG) study. Eligibility for PD cases included recent diagnosis (within 3–5 years), California residency for at least 5 years, confirmation by a movement disorder specialist, and absence of other neurological or terminal illnesses. Controls were either household members (to account for shared environmental exposures) or community members (to avoid overmatching for household factors), and were excluded if they had PD or a terminal illness. All participants had not taken antibiotics for at least 3 months prior to sampling and were not immunocompromised. The mean age was 72 years, and about 80% were white, with a higher proportion of males among PD cases (67%) than controls (34%).

Most important findings

The study found that PD patients exhibited significantly reduced gut microbiome alpha diversity (Shannon index, p=0.04) and distinct beta diversity (Bray-Curtis dissimilarity, p=0.002) compared to controls. Taxonomically, PD patients had increased relative abundance of three phyla: Proteobacteria, Verrucomicrobiota, and Actinobacteriota. Five genera were notably elevated in PD: Akkermansia (Verrucomicrobiota), Enterococcus, Hungatella, and two genera from the Ruminococcaceae family (UBA1819 and DTU089). These differences remained robust after adjusting for covariates (sex, race, age, sequencing platform), but some associations (e.g., Actinobacteriota) were attenuated when controlling for constipation or when restricting to household control analyses, highlighting the importance of both clinical features and environmental confounders.

Predicted metagenomic analysis (using PICRUST2) revealed 35 MetaCyc pathways that differed significantly between PD patients and controls, including those involved in biosynthesis, degradation, energy generation, and glycan metabolism. Within PD patients, specific microbial features tracked with clinical subtypes and disease duration: higher Verrucomicrobiota (Akkermansia) was associated with the postural instability gait dysfunction (PIGD) subtype, while Synergistota, DTU089, and other genera were linked to longer disease duration. Pathways related to aromatic compound degradation were reduced in those with longer PD duration. There were no significant associations between gut microbiome composition and L-DOPA dose.

Key implications

This study reinforces the existence of distinct gut microbiome signatures in PD patients, with specific enrichment of certain phyla (notably Proteobacteria and Verrucomicrobiota/Akkermansia) and functional metabolic pathways. The findings suggest that the gut microbiome is not only altered in PD but that these alterations relate to key clinical features, such as disease subtype and duration. The robust linkage of Akkermansia with PD—especially the PIGD motor subtype—adds to emerging evidence of its potential role as a biomarker or modulator of disease progression. The identification of altered metabolic pathways, such as increased polyamine biosynthesis and reduced degradation of aromatic compounds, highlights possible mechanisms by which the microbiome could influence neurodegeneration or reflect compensatory responses. Clinically, these microbiome signatures could inform future biomarker development, early detection strategies, or even microbiome-targeted interventions for PD management and prevention.

Citation

Zhang K, Paul KC, Jacobs JP, Chou H-C, Duarte Folle A, Del Rosario I, Yu Y, Bronstein JM, Keener AM, Ritz B. Parkinson’s disease and the gut microbiome in rural California. J Parkinsons Dis. 2022;12(6):2441–2452. doi:10.3233/JPD-223500