Causal Relationships Between the Gut Microbiota, Inflammatory Cytokines, and Amyotrophic Lateral Sclerosis: A Mendelian Randomization Analysis
Brain and Behavior, 2025
Changqing L., Leying Y., Caiyun M., Hebao W., Laiguo H., Xiaojiang Z.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Neurology | Pathophysiology | Plasma |  Olink Target 96 |
Abstract
Background
The relationship between gut microbiota (GM) and amyotrophic lateral sclerosis (ALS) is well‐documented. However, the causal nature of this association and the potential mediating role of inflammatory cytokines (ICs) have yet to be elucidated.
Methods
We performed Mendelian randomization (MR) analyses utilizing data derived from genome‐wide association studies (GWAS) of GM, ICs, and ALS. Initially, we conducted bidirectional two‐sample MR analysis to determine the causal relationships between GM, ICs, and ALS. Subsequently, a two‐step MR mediation analysis was performed to investigate the role of ICs as mediators. The primary statistical approach was the inverse variance weighted (IVW) method.
Results
Through MR analysis, we identified one positive causal relationship and three negative causal relationships between GM and ALS. There was one positive association and one negative association between ICs and ALS. In addition, ICs do not appear to mediate the pathway from GM to ALS.
Conclusion
This study established a causal relationship between GM, ICs, and ALS, suggesting that ICs do not function as mediators in the pathway from GM to ALS. These findings provide new perspectives on potential ALS prevention and treatment strategies.