Distinct gut and oral microbial profiles differentiate patients with symmetric/asymmetric Parkinson's disease

Parkinson's disease (PD) presents heterogeneous motor patterns. Symmetric and asymmetric phenotypes potentially reflect distinct pathogenic origins as proposed by the Synuclein Origin and Connectome (SOC) model. However, differences in gut and oral microbiota between these PD subtypes remain unclear.

To compare gut and oral microbiota characteristics in symmetric and asymmetric PD patients and explore correlations with clinical features.

Thirty symmetric and twenty-three asymmetric PD patients were enrolled. Fecal and salivary microbiota were analyzed using 16S rRNA sequencing, and clinical features were evaluated using standard motor and non-motor scales.

The symmetric group showed higher H-Y stage and scores of MDS-UPDRS II, DSFS, MMSE, and MoCA than the asymmetric group (all p < 0.05). Gut and oral microbiota structures differed significantly, with higher gut microbial α-diversity in the symmetric group. Desulfobacterota and related taxa were enriched in symmetric PD and correlated positively with GCSI scores, while butyrate-producing bacteria predominated in asymmetric PD. Predicted metabolic analyses indicated enrichment of six pathways in asymmetric gut microbiota and nine pathways enriched in symmetric oral microbiota.

Symmetric and asymmetric PD are associated with distinct clinical and gut microbiota features, including predicted functional profiles. This aligns with the SOC model of divergent disease origins and mechanisms and points to the microbiota as a candidate factor in PD heterogeneity, offering new testable hypotheses for future research.