Colonic bacterial composition in Parkinson’s disease Original paper

What was studied?

This original research article investigated colonic microbiota in Parkinson’s disease, examining whether altered gut microbial communities contribute to intestinal inflammation and the misfolding of alpha-synuclein in the colon. The researchers focused on both mucosa-associated and fecal bacterial populations, using 16S rRNA gene amplicon sequencing to characterize microbial profiles. They also explored predicted microbial functional pathways to understand whether dysbiosis in Parkinson’s disease (PD) may influence inflammation, oxidative stress, and epithelial barrier dysfunction. By comparing microbial signatures in PD patients versus healthy controls, the study aimed to identify specific bacterial taxa and functional pathways potentially involved in PD pathogenesis.

Who was studied?

The study included 38 individuals diagnosed with PD and 34 healthy control participants recruited from clinical centers at Rush University Medical Center. PD participants ranged widely in disease duration and included both treatment-naïve and medicated individuals. Controls were free of digestive and neurodegenerative disease and had no recent exposure to antibiotics or probiotics. Sigmoid mucosal biopsies and fecal samples were collected from each participant, enabling paired analysis of mucosal-associated and luminal microbiota. Dietary intake, constipation scores, and clinical measures of PD severity were also recorded to assess potential confounding variables. Statistical analyses confirmed that diet, BMI, age, and medication use had limited influence on the microbial differences observed between groups.

Most important findings

The microbial communities of PD patients differed markedly from controls, with fecal samples showing more pronounced alterations than mucosal samples. PD patients exhibited significantly reduced abundance of putative anti-inflammatory butyrate-producing genera such as Blautia, Coprococcus, Roseburia, and Faecalibacterium. These taxa play essential roles in maintaining epithelial barrier integrity through short-chain fatty acid (SCFA) production, particularly butyrate. Their depletion suggests an impaired colonic environment favoring inflammation. In contrast, mucosal samples from PD subjects were enriched with proinflammatory Ralstonia (Proteobacteria), and fecal samples showed elevated Akkermansia, Oscillospira, and Bacteroides. Functional metagenomic predictions revealed reduced metabolic and biosynthetic pathway activity in PD, alongside increased lipopolysaccharide (LPS) biosynthesis and type III secretion system genes—features typically associated with pathogenicity. These microbial signatures collectively suggest a proinflammatory dysbiosis capable of contributing to oxidative stress, intestinal permeability, and subsequent propagation of alpha-synuclein pathology.

Key implications

The study demonstrates that dysbiosis—characterized by reduced SCFA-producing bacteria and increased proinflammatory taxa—is closely associated with PD. These microbial shifts may promote mucosal inflammation, oxidative injury, and gut barrier dysfunction, all of which could precede or exacerbate alpha-synuclein aggregation. The enrichment of LPS-related and type III secretion pathways further supports the hypothesis that microbial products contribute to enteric and central neuroinflammation. These findings build a mechanistic bridge between gut microbial imbalance and PD progression, highlighting therapeutic opportunities for microbiome-targeted interventions such as prebiotics, probiotics, and dietary modulation.

Citation

Keshavarzian A, Green SJ, Engen PA, et al. Colonic bacterial composition in Parkinson’s disease.Movement Disorders. 2015;30(10):1351-1360. doi:10.1002/mds.26307