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Updated: Sep 16, 2025
Microbiota Analysis Using Two-step PCR and Next-generation 16S rRNA Gene Sequencing
Published on: October 15, 2019
Dissecting Causal Relationships Between Gut Microbiota, Immunocyte Phenotype, and Migraine: A Mendelian Randomization
Yupei Lai1, Yike Liu1, Jiahao Chen2
1The Third Affiliated Hospital of Southern Medical University, Guangzhou, China.
Background:
Migraines impose a substantial economic and societal burden, yet their underlying mechanisms remain poorly understood. While observational studies suggest associations between gut microbiota dysbiosis, immunophenotypic alterations, and migraine risk, causal evidence is lacking. This study leverages Mendelian Randomization to investigate the causal relationship between gut microbiota and migraine while exploring the mediating role of immune traits in this association.
Methods:
We employed a two-sample, two-step Mendelian Randomization approach to examine the mediating effects of immunocyte phenotypes on the relationship between gut microbiota and migraine outcomes, including migraine with aura and migraine without aura. The primary analysis utilized inverse-variance weighted estimation, supplemented by sensitivity analyses to ensure robustness. Summary statistics for gut microbiota were sourced from the MiBioGen consortium and NHGRI-EBI, immunocyte phenotypes from the GWAS catalog, and migraine data from the FinnGen consortium. Next, we evaluated Prevotella histicola level by qPCR.
Results:
Our analysis identified suggestive associations between 34 gut microbiota taxa and migraine subtypes. Notably, Family Bifidobacteriaceae (id.433, PIVW: 1.51×10⁻⁵, ORIVW: 0.861, 95% CI: 0.765-0.970) and Order Bifidobacteriales (id.432, PIVW: 1.51×10⁻⁵, ORIVW: 0.861, 95% CI: 0.765-0.970) demonstrated strong causal links to a reduced risk of migraine. Mediation analysis revealed that HLA-DR on monocytes mediated 7.74% of the causal pathway from Genus Prevotella9 (id.11183, PIVW: 0.002, ORIVW: 0.834, 95% CI: 0.744-0.936) to MA.
Conclusions:
This study provides robust evidence of a causal relationship between Bifidobacteriaceae and a decreased risk of migraine. Furthermore, we identify HLA-DR on monocytes as a key inflammatory mediator in the protective effect of Prevotella against migraine with aura. These findings highlight the potential of gut microbiota modulation and immune-targeted therapies in migraine prevention and treatment, offering novel insights into the gut-brain-immune axis in migraine pathogenesis.
Insights
Certain gut bacteria, like Bifidobacteriaceae, may causally reduce migraine risk. Immune cells, specifically HLA-DR on monocytes, mediate this protective effect for migraine with aura, suggesting new therapeutic avenues.
Area of Science:
- Genetics
- Microbiology
- Immunology
Background:
- Migraines represent a significant health and economic burden.
- The precise mechanisms underlying migraine remain unclear.
- Observational studies suggest links between gut microbiota dysbiosis, immune alterations, and migraine, but causal evidence is limited.
Purpose of the Study:
- To investigate the causal relationship between gut microbiota and migraine using Mendelian Randomization.
- To explore the mediating role of immune traits in the gut microbiota-migraine association.
- To analyze causal links for specific migraine subtypes (migraine with aura and without aura).
Main Methods:
- A two-sample, two-step Mendelian Randomization approach was employed.
- Inverse-variance weighted estimation was the primary analytical method, supported by sensitivity analyses.
- Summary statistics were obtained from large-scale consortia for gut microbiota (MiBioGen, NHGRI-EBI), immunocyte phenotypes (GWAS Catalog), and migraine (FinnGen).
Main Results:
- Suggestive causal associations were found between 34 gut microbiota taxa and migraine subtypes.
- Family Bifidobacteriaceae and Order Bifidobacteriales showed significant causal links to reduced migraine risk.
- HLA-DR on monocytes was identified as a mediator in the protective pathway from Genus Prevotella to migraine with aura.
Conclusions:
- This study provides robust evidence for a causal link between Bifidobacteriaceae and decreased migraine risk.
- HLA-DR on monocytes acts as a key inflammatory mediator in the protective effect of Prevotella against migraine with aura.
- Findings suggest potential for gut microbiota modulation and immune-targeted therapies in migraine management.
