Dissecting Causal Links Between Gut Microbiota, Inflammatory Cytokines, and Parkinson's Disease: A Mendelian Randomization Study.

Background: The association between gut microbiota (GM) and Parkinson's disease (PD) has been well established, but whether there is a causal relationship between the two and whether inflammatory cytokines (ICs) act as mediators remain unclear.

Methods: We utilized the summary databases of large-scale genome-wide association studies (GWAS) conducting Mendelian randomization (MR) analyses to investigate the causal relationships between GM, ICs, and PD. The inverse-variance weighted (IVW) method was primarily used to identify GM and ICs associated with PD and to examine the mediating role of ICs, supplemented by MR Egger and weighted median.

Results: Through MR analysis, we identified three positive causal relationships and six negative causal relationships between GM and PD. Additionally, there were three positive associations and five negative associations between ICs and PD. However, after adjusting for FDR, none of these associations were significant. In reverse MR analysis, we also found causal relationships between PD and various GM and ICs. Further, two-step MR analysis indicated that the negative impact of phylum Actinobacteria on PD may be mediated through Fms-related tyrosine kinase 3 ligand levels.

Conclusion: This study strengthens the link between GM and the risk of PD, while also revealing the potential mediating role of ICs in the causal relationships between these factors.