Bidirectional mediation between microbiota and immune system in Parkinson disease: A two-sample Mendelian...

Area of Science:

• Genetics
• Microbiology
• Immunology
• Neuroscience

Background:

• Emerging evidence suggests a connection between the gut microbiome, skin microbiome, immune system, and Parkinson disease (PD).
• The precise causal links and biological mechanisms underlying these associations remain largely undetermined.

Purpose of the Study:

• To investigate the causal relationships between gut microbiota, skin microbiota, immune cell phenotypes, inflammatory proteins, and Parkinson disease (PD).
• To explore potential mediating pathways in the "microbiota-immune-PD" axis using genetic data.

Main Methods:

• A two-sample Mendelian randomization analysis was performed using genome-wide association study summary data.
• Included were 473 gut microbial taxa, 150 skin microbial taxa, 731 immune cell phenotypes, and 91 inflammatory proteins.
• Sensitivity and mediation analyses were conducted to ensure robustness and identify biological pathways.

Main Results:

• Significant causal associations were found between 16 gut microbial taxa, 2 skin microbial taxa, 19 immune cell phenotypes, and 4 inflammatory proteins with PD.
• Two-step mediation analyses identified "microbiota-immune-PD" and "immune-microbiota-PD" pathways.
• Specific examples include mediation by HLA DR on myeloid dendritic cells and the bacterium Bifidobacterium adolescentis, with IL-18 showing substantial mediation via Lentimicrobiaceae.

Conclusions:

• This study provides novel genetic evidence supporting the role of the microbiota-immune axis in Parkinson disease pathogenesis.
• The findings highlight specific microbial taxa, immune cells, and inflammatory proteins as potential therapeutic targets for PD intervention.