Unraveling gut microbiota in Parkinson’s disease and atypical parkinsonism Original paper

What was studied?

This study investigated gut microbiota in Parkinson’s disease by characterizing fecal microbial composition across idiopathic Parkinson’s disease (PD), atypical Parkinsonism—multiple system atrophy (MSA), and progressive supranuclear palsy (PSP)—and healthy controls. Using 16S rRNA sequencing, researchers analyzed microbial abundance, diversity, and community structure while controlling for major microbiome-shaping confounders, including diet, medications, age, and constipation. The study also evaluated how changes in gut microbiota related to disease duration, motor and nonmotor symptoms, and clinical phenotypes. A notable aspect was the inclusion of a substantial cohort of de novo, drug-naïve PD patients, allowing assessment of early disease signatures without medication effects.

Who was studied?

The cohort included 350 individuals: 193 idiopathic PD patients (39 de novo), 22 MSA patients, 22 PSP patients, and 113 healthy controls matched for age, BMI, and geographic region. PD participants were stratified into early, mid, and advanced disease stages, with extensive clinical phenotyping using UPDRS, Hoehn & Yahr staging, cognitive assessment, and nonmotor symptom evaluation. Strict exclusion criteria minimized confounding from antibiotics, probiotics, gastrointestinal diseases, and immunosuppressive therapies. Dietary intake was captured through 10-day food diaries and validated 24-hour recalls, enabling rigorous adjustment for diet-related microbial influences. Stool samples were collected and processed under standardized laboratory conditions.

Most important findings

After adjusting for confounders, PD patients showed a consistent reduction of Lachnospiraceae—especially Roseburia—and increased Verrucomicrobia (Akkermansia), Proteobacteria, Lactobacillaceae, Christensenellaceae, and certain Actinobacteria. The reduced Lachnospiraceae signature appeared uniquely in de novo PD, suggesting an early microbiome alteration. Disease duration was linked to progressive increases in Lactobacillaceae and Akkermansia and further declines in Lachnospiraceae. Table 2 (page 7) linked high Lactobacillaceae and low Lachnospiraceae with cognitive impairment, worse UPDRS III scores, gait disturbance, and postural instability. Functional predictions in de novo PD showed altered metabolic pathways involving amino acids, lipids, cofactors, xenobiotic degradation, and ubiquitin-related processes.

Key implications

The findings suggest that gut dysbiosis—particularly the early and persistent depletion of Lachnospiraceae—may influence PD pathophysiology through impaired short-chain fatty acid production, epithelial barrier dysfunction, and immune activation. The association of Lactobacillaceae and Christensenellaceae with worse clinical features raises the possibility that some microbial shifts reflect compensatory or disease-driven processes rather than causal drivers. Similar microbiota alterations in MSA and PSP indicate shared gut–brain axis disturbances across Parkinsonian syndromes. The study underscores the need for prospective, mechanistic investigations focused on early disease stages to clarify microbial contributions to neurodegeneration and clinical variability.

Citation

Barichella M, Severgnini M, Cilia R, et al. Unraveling gut microbiota in Parkinson’s disease and atypical Parkinsonism. Movement Disorders. 2018;33(9):1-10