Parkinson’s disease and Parkinson’s disease medications have distinct signatures of the gut microbiome Original paper

What was studied?

This study investigated Parkinson’s disease gut microbiome signatures by analyzing whether individuals with Parkinson’s disease (PD) exhibit a distinct pattern of gut microbial dysbiosis compared to neurologically healthy controls. The researchers aimed to disentangle the direct effects of PD from those created by medication use, diet, geography, gastrointestinal symptoms, and numerous demographic variables. Using 16S rRNA sequencing of stool samples, the team assessed microbial composition, taxonomic differences, and predicted functional metabolic pathways. A crucial component involved identifying microbial families and genera consistently altered in PD, such as Bifidobacteriaceae, Verrucomicrobiaceae, Christensenellaceae, Lactobacillaceae, Lachnospiraceae, Pasteurellaceae, and Tissierellaceae. They also evaluated metabolic pathway shifts using PICRUSt, focusing on pathways involved in carbohydrate processing, xenobiotic degradation, energy metabolism, and vitamin and cofactor biosynthesis.

Who was studied?

A total of 197 Parkinson’s disease cases and 130 controls were recruited from three U.S. regions: Seattle (WA), Atlanta (GA), and Albany (NY). All PD participants were diagnosed by movement disorder specialists using modified UK Brain Bank criteria. Controls were required to be free of neurodegenerative conditions. The dataset included individuals with diverse ages, diets, medication exposures, and gastrointestinal histories. Metadata detailing 39 potential confounders were collected, including PD medication classes (COMT inhibitors, anticholinergics, carbidopa/levodopa, dopamine agonists, amantadine, MAO-B inhibitors), lifestyle variables, bowel habits, BMI, diet quality, and stool sample transit time. After quality filtering, 327 participants remained for analysis, providing one of the largest and most comprehensively annotated PD microbiome cohorts to date.

Most important findings

The study demonstrated a clear alteration in gut microbial composition in PD, independent of major confounders. Distinct PD-associated microbial signatures included increased Bifidobacteriaceae, Lactobacillaceae, Christensenellaceae, Verrucomicrobiaceae, and Tissierellaceae, alongside reduced Lachnospiraceae, Ruminococcaceae (notably Faecalibacterium), and Pasteurellaceae. A subset of taxa, such as Bifidobacterium OTUs, was partially medication-driven, especially linked to COMT inhibitors and anticholinergics. Long disease duration (>10 years) amplified some changes, particularly the Ruminococcaceae. Functionally, 26 metabolic pathways differed significantly, including increased xenobiotic degradation (e.g., atrazine, chloroalkane, naphthalene pathways), shifts in carbohydrate metabolism, reduced butyrate-related pathways (e.g., butyrate kinase), and altered biosynthesis of cofactors, lipids, and amino acids. These patterns support a mechanistic model where microbial changes may influence inflammation, gut permeability, and neuroimmune activity relevant to PD progression.

Key implications

These findings strongly support the presence of Parkinson’s disease–associated gut microbiome dysbiosis, providing robust microbial and functional signatures relevant to biomarker development. The substantial involvement of SCFA-producing taxa, particularly Lachnospiraceae and Faecalibacterium, reinforces hypotheses linking PD to impaired SCFA signaling and gut–brain immune modulation. The identification of medication-driven microbial shifts highlights the need to consider drug–microbiome interactions in clinical care and future microbiome research. Increased xenobiotic degradation pathways also raise the possibility that environmental toxicants contribute to dysbiosis and disease progression. Overall, these results offer testable hypotheses for mechanistic models of PD and define candidate microbial markers suitable for integration into microbiome signature databases.

Citation

Hill-Burns EM, Debelius JW, Morton JT, et al. Parkinson’s disease and PD medications have distinct signatures of the gut microbiome.Mov Disord. 2017;32(5):739-749. doi:10.1002/mds.26942