Qu Kang, Li Ming-Xi, Gan Lin, Cui Zi-Ting, Li Jia-Jia, Yang Rong, Dong Ming
Department of Neurology and Neuroscience Center, The First Hospital of Jilin University, Changchun, China.
Front Microbiol. 2024 Apr 16;15:1325047. doi: 10.3389/fmicb.2024.1325047. eCollection 2024.
It has been suggested in several observational studies that migraines are associated with the gut microbiota. It remains unclear, however, how the gut microbiota and migraines are causally related.
We performed a bidirectional two-sample mendelian randomization study. Genome-wide association study (GWAS) summary statistics for the gut microbiota were obtained from the MiBioGen consortium ( = 18,340) and the Dutch Microbiota Project ( = 7,738). Pooled GWAS data for plasma metabolites were obtained from four different human metabolomics studies. GWAS summary data for migraine (cases = 48,975; controls = 450,381) were sourced from the International Headache Genetics Consortium. We used inverse-variance weighting as the primary analysis. Multiple sensitivity analyses were performed to ensure the robustness of the estimated results. We also conducted reverse mendelian randomization when a causal relationship between exposure and migraine was found.
(OR = 1.12, 95% CI: 1.05-1.20) was a risk factor for migraine. (OR = 0.93, 95% CI: 0.88-0.99), ( group; OR = 0.94, 95% CI: 0.90-0.98), and (OR = 0.97, 95% CI: 0.94-1.00) may have a suggestive association with a lower migraine risk. Functional pathways of methionine synthesis (OR = 0.89, 95% CI: 0.83-0.95) associated with microbiota abundance and plasma hydrocinnamate (OR = 0.85, 95% CI: 0.73-1.00), which are downstream metabolites of and , respectively, may also be associated with lower migraine risk. No causal association between migraine and the gut microbiota or metabolites was found in reverse mendelian randomization analysis. Both significant horizontal pleiotropy and significant heterogeneity were not clearly identified.
This Mendelian randomization analysis showed that was associated with an increased risk of migraine, while some bacteria in the gut microbiota may reduce migraine risk. These findings provide a reference for a deeper comprehension of the role of the gut-brain axis in migraine as well as possible targets for treatment interventions.
多项观察性研究表明偏头痛与肠道微生物群有关。然而，肠道微生物群与偏头痛之间的因果关系仍不清楚。
我们进行了一项双向双样本孟德尔随机化研究。肠道微生物群的全基因组关联研究（GWAS）汇总统计数据来自MiBioGen联盟（n = 18340）和荷兰微生物群项目（n = 7738）。血浆代谢物的汇总GWAS数据来自四项不同的人类代谢组学研究。偏头痛的GWAS汇总数据（病例 = 48975；对照 = 450381）来自国际头痛遗传学联盟。我们使用逆方差加权作为主要分析方法。进行了多项敏感性分析以确保估计结果的稳健性。当发现暴露与偏头痛之间存在因果关系时，我们还进行了反向孟德尔随机化分析。
（比值比 = 1.12，95%置信区间：1.05 - 1.20）是偏头痛的一个危险因素。（比值比 = 0.93，95%置信区间：0.88 - 0.99）、（组；比值比 = 0.94，95%置信区间：0.90 - 0.98）和（比值比 = 0.97，95%置信区间：0.94 - 1.00）可能与较低的偏头痛风险存在提示性关联。与微生物群丰度相关的甲硫氨酸合成功能途径（比值比 = 0.89，95%置信区间：0.83 - 0.95）和血浆氢化肉桂酸（比值比 = 0.85，95%置信区间：0.73 - 1.00），分别是和的下游代谢物，也可能与较低的偏头痛风险相关。在反向孟德尔随机化分析中未发现偏头痛与肠道微生物群或代谢物之间存在因果关联。未明确识别出显著的水平多效性和显著的异质性。
这项孟德尔随机化分析表明与偏头痛风险增加有关，而肠道微生物群中的一些细菌可能会降低偏头痛风险。这些发现为更深入理解肠道 - 脑轴在偏头痛中的作用以及治疗干预的可能靶点提供了参考。
