Causal Pathways Linking Gut Microbiota, Serum Metabolites, and Meningioma Risk: A Mendelian Randomization Analysis

Area of Science:

• Neuro-oncology
• Microbiome research
• Metabolomics

Background:

• Meningioma is a common adult central nervous system (CNS) tumor with an unclear origin.
• The gut microbiota-CNS axis is implicated in neurological disorders, but its role in meningioma is unknown.

Purpose of the Study:

• To investigate causal relationships between gut microbial taxa, serum metabolites, and meningioma using Mendelian randomization (MR).
• To explore potential mediation of meningioma risk by serum metabolites.

Main Methods:

• A two-sample MR framework utilizing genome-wide association study data for 473 gut microbial taxa, 1400 serum metabolites, and meningioma.
• Inverse variance weighted, MR-Egger, and weighted median methods for primary and complementary analyses.
• Two-step MR for mediation analysis and sensitivity analyses for robustness.

Main Results:

• Nineteen gut microbial taxa showed a causal association with meningioma risk.
• Forty-nine serum metabolites were potentially causally linked, involving inflammatory, hormonal, and lipid pathways.
• Arachidonate (20:4n6) was identified as a potential mediator between a specific microbial group (CAG-873 sp001701165) and meningioma.

Conclusions:

• This research provides novel insights into the gut microbiota's and metabolites' causal roles in meningioma development.
• Findings suggest potential new strategies for meningioma prevention and treatment targeting the gut microbiome and metabolic pathways.