Altered gut microbiota in Parkinson’s disease patients with motor complications Original paper

What was studied?

This multicenter Japanese cohort study examined altered gut microbiota in Parkinson’s disease with motor complications by comparing fecal microbiome profiles of patients with and without motor complications, particularly wearing-off and dyskinesia. Using 16S rRNA gene sequencing, the authors characterized bacterial genera and tested whether specific taxa were independently associated with motor complications after controlling for clinical covariates. They focused on relative abundance shifts rather than absolute counts and applied analysis of covariance with Bonferroni correction to identify robust microbiome signatures. The central question was whether particular microbial patterns, beyond general PD-related dysbiosis, track specifically with advanced disease phenotypes such as wearing-off, pointing to candidate microbiome markers for progression or treatment-response complications.

Who was studied?

The study enrolled 223 individuals with clinically diagnosed Parkinson’s disease from four movement disorder centers across Japan, representing a real-world, treated PD population rather than de novo cases. All participants were receiving dopaminergic therapy, and 47.5% had wearing-off phenomena, while 21.9% exhibited dyskinesia. The cohort, therefore, reflects mid- to late-stage PD with a substantial burden of motor complications. Clinical variables, including age and disease duration, were incorporated into the statistical models assessing microbiota differences, allowing the authors to distinguish microbial changes linked to motor complications themselves from those simply reflecting older age or longer-standing disease. No healthy control group is described in the abstract; the key comparison is within PD patients with versus without wearing-off or dyskinesia.

Most important findings

The most clinically relevant microbiome signals emerged in relation to wearing off rather than dyskinesia. Among 98 identified bacterial genera, two taxa showed robust and directionally opposite associations with wearing off after Bonferroni correction. Patients with wearing-off had a significantly decreased relative abundance of Lachnospiraceae genus Blautia and a markedly increased relative abundance of Lactobacillaceae genus Lactobacillus (both p <0.0001). ANCOVA models adjusting for confounders showed that age, disease duration, and wearing-off were independent predictors of lower Blautia abundance, suggesting Blautia depletion reflects both advancing disease and motor fluctuations. In contrast, wearing-off was the only independent risk factor associated with increased Lactobacillus abundance, implying a more specific link between Lactobacillus expansion and motor fluctuations. Interestingly, once stringent correction was applied, dyskinesia was no longer associated with significant gut microbiome shifts, indicating that, in this cohort, dyskinesia did not define a distinct gut microbial signature beyond general PD-related changes.

Key implications

For clinicians and microbiome databases, this study highlights Blautia depletion and Lactobacillus enrichment as candidate microbial signatures of motor complication–associated PD. Blautia, a short-chain fatty acid–producing genus within Lachnospiraceae, is frequently linked to gut barrier integrity and anti-inflammatory effects; its reduction may exacerbate neuroinflammatory or gut–brain axis dysfunction in advanced PD. Conversely, elevated Lactobacillus, a genus often influenced by diet, probiotics, and gastric acid suppression, may interact with levodopa metabolism or intestinal transit, potentially modulating wearing-off. While causality cannot be inferred, these genera are high-value targets for future interventional or longitudinal studies and for inclusion as specific features in PD microbiome signature panels. Clinically, the findings support the concept that motor complications are not purely pharmacokinetic or striatal phenomena but may also be reflected in, or partly shaped by, gut microbial shifts.

Citation

Takahashi K, Nishiwaki H, Ito M, et al. Altered gut microbiota in Parkinson’s disease patients with motor complications. Parkinsonism Relat Disord. 2022;95:11-17. doi:10.1016/j.parkreldis.2021.12.012