Related Experiment Video
Updated: Jun 6, 2025
Author Spotlight: Exploring Non-Motor Symptoms in Parkinson's Disease
Published on: September 22, 2023
Dissecting Causal Links Between Gut Microbiota, Inflammatory Cytokines, and Parkinson's Disease: A Mendelian
Ma Caiyun1, Wen Hebao1,2, Ye Wenhao1
1Anhui Engineering Research Center for Neural Regeneration Technology and Medical New Materials, Bengbu Medical University, Bengbu, China.
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.
Insights
This study investigates the causal link between gut microbiota (GM) and Parkinson's disease (PD), exploring the mediating role of inflammatory cytokines (ICs). Findings suggest a connection, with potential cytokine mediation pathways identified.
Area of Science:
- Neuroscience
- Microbiology
- Genetics
Background:
- The association between gut microbiota (GM) and Parkinson's disease (PD) is known, but causality and the role of inflammatory cytokines (ICs) as mediators are unclear.
- Investigating these relationships is crucial for understanding PD pathogenesis.
Purpose of the Study:
- To investigate the causal relationships between GM, ICs, and PD using Mendelian randomization (MR).
- To examine the potential mediating role of ICs in the GM-PD association.
Main Methods:
- Utilized large-scale genome-wide association studies (GWAS) summary databases.
- Performed Mendelian randomization (MR) analyses, primarily using the inverse-variance weighted (IVW) method.
- Employed MR Egger and weighted median methods for supplementary analysis and two-step MR for mediation analysis.
Main Results:
- Identified several potential causal relationships between specific GM and PD, and between ICs and PD, though none remained significant after FDR adjustment.
- Reverse MR analysis indicated causal links between PD and various GM and ICs.
- Two-step MR suggested that phylum Actinobacteria may negatively impact PD risk, potentially mediated by Fms-related tyrosine kinase 3 ligand levels.
Conclusions:
- Strengthened the evidence linking gut microbiota to Parkinson's disease risk.
- Revealed the potential mediating role of inflammatory cytokines in the complex interplay between gut microbiota and PD.
