The Gut Microbiome in Parkinson’s Disease: A Longitudinal Study of the Impacts on Disease Progression and the Use of Device-Assisted Therapies Original paper

What was studied?

This original research investigated the longitudinal dynamics of the gut microbiome in Parkinson’s disease (PD), focusing on temporal stability, disease progression, and the impact of device-assisted therapies (DAT) such as Deep Brain Stimulation (DBS) and Levodopa-Carbidopa Intestinal Gel (LCIG). The study compared gut microbiota profiles between PD patients and matched household controls (HCs) over 12 months, aiming to identify persistent microbiome signatures associated with PD and to assess whether microbiota composition could predict disease progression. Additionally, it evaluated how DAT initiation influenced gut microbiome structure, both short-term and long-term. The study also explored the integration of microbiota and dietary data to enhance the prediction of disease progression, providing insights for the development of microbiome-based biomarkers in PD.

Who was studied?

The study enrolled 74 PD patients and 74 household controls, each sampled at baseline, 6 months, and 12 months. Participants were recruited from movement disorder and neurology clinics in Sydney, Australia. PD patients met the UK Parkinson’s Disease Society Brain Bank Diagnostic Criteria, and controls were cohabiting spouses or relatives with similar dietary habits. A subgroup of 19 PD patients initiating DAT (9 DBS, 10 LCIG) was separately evaluated at the same intervals pre- and post-therapy. Exclusion criteria included secondary Parkinsonism, severe comorbidities affecting participation, and recent antibiotic or probiotic use. Demographic, clinical, dietary, and biochemical data were meticulously collected, and stool samples underwent 16S rRNA gene sequencing to characterize the microbial community.

Most important findings

The study revealed persistent, significant differences in gut microbiome composition between PD patients and controls across all time points, after controlling for confounding factors such as age, sex, diet, and constipation. Notably, PD patients demonstrated a consistent underrepresentation of several short-chain fatty acid (SCFA)-producing bacterial genera, particularly Butyricicoccus, Fusicatenibacter, Lachnospiraceae ND3007 group, and Erysipelotrichaceae UCG-003. These findings suggest a reduced butyrogenic potential in the PD microbiome, which may contribute to gut barrier dysfunction and inflammation. At the family level, PD patients had a persistent overrepresentation of Lactobacillaceae and an underrepresentation of Butyricicoccaceae.

When stratifying PD patients by disease progression, the genus Barnesiella and family Barnesiellaceae appeared underrepresented in faster-progressing patients at baseline and 12 months, though no single taxa consistently differentiated progression groups across all time points. Integration of dietary data, especially protein intake as a proportion of energy, improved the predictive capacity for disease progression from an area under the curve (AUC) of 0.58 (microbiome alone) to 0.64 (combined model).

Regarding DAT, both DBS and LCIG induced variable, non-persistent shifts in gut microbiome composition, with some therapy-specific trends: persistent overrepresentation of Prevotella post-DBS and a trend toward increased Roseburia post-LCIG. However, no consistent long-term microbial signature was attributed to DAT exposure.

Key implications

This study strengthens the evidence that PD is characterized by a persistent depletion of butyrate-producing bacteria, potentially underpinning gut leakiness and inflammation along the gut-brain axis. These microbiome alterations are stable over time and relatively unaffected by device-assisted therapies, indicating their potential as core biomarkers of PD. While individual taxa linked to disease progression were inconsistent, the combination of gut microbiome profiling and dietary data modestly enhanced the ability to predict progression rate, highlighting the multifactorial nature of PD pathogenesis and the importance of considering both microbial and nutritional factors. The findings pave the way for future, larger longitudinal studies to refine microbiome-based biomarkers for diagnosis and monitoring of PD, and suggest that interventions aiming to restore butyrogenic bacteria or SCFA production might be therapeutically beneficial.

Citation

Lubomski M, Xu X, Holmes AJ, Muller S, Yang JYH, Davis RL, Sue CM. The Gut Microbiome in Parkinson’s Disease: A Longitudinal Study of the Impacts on Disease Progression and the Use of Device-Assisted Therapies. Front Aging Neurosci. 2022;14:875261. doi:10.3389/fnagi.2022.875261