作者：郭玉梦1 ，崔杨霖1 ，孔雨晨1 ，高磊2 ，张宪忠2

单位：

1.250014山东省济南市，山东中医药大学　2.276800山东省日照市中医医院中医经典科

单位（英文）：

1.Shandong University of Traditional Chinese Medicine, Jinan 250014, China 2.Classic Department of Traditional Chinese medicine, Rizhao Hospital of Traditional Chinese Medicine, Rizhao 276800, China

关键词：

丛集性头痛；胃肠道微生物组；肠道菌群；孟德尔随机化分析；因果关系

关键词（英文）：

Cluster headache; Gastrointestinal microbiome; Intestinal flora; Mendelian randomization analysis; Causation

中图分类号：

R 741.041

DOI：

10.12114/j.issn.1008-5971.2024.00.061

基金项目：

第七批全国老中医药专家学术经验继承工作项目（国中医人教函（2022）76号）；山东省中医临床优秀人才培养项 目（鲁卫函（2022）233号）；日照市重点研发计划项目（公益性科技攻关）（2021ZDYF020212）

摘要：

　目的　采用两样本孟德尔随机化（MR）分析探讨肠道菌群与丛集性头痛（CH）的因果关系。方法 肠道菌群数据集来自MiBioGen联盟的汇总数据，共涉及1 053 032 560个单核苷酸多态性（SNP）；CH数据集来自 R9版本的芬兰数据库，共涉及20 167 676个SNP。本研究主要采用逆方差加权法（IVW）进行MR分析，以探讨肠道菌 群与CH的潜在因果关系，并采用错误发现率（FDR）校正P值；其次，以MR-Egger回归、加权中位数法（WME）、 加权众数法（WM）、简单众数法（SM）作为IVW的补充方法。采用IVW、MR-Egger回归分析肠道菌群与CH的反向 因果关系。结果　IVW分析结果显示，放线菌门是CH的危险因素〔OR=1.786，95%CI（1.154～2.764），P=0.009， PFDR=0.046〕，粪球菌属1是CH的保护因素〔OR=0.563，95%CI（0.355～0.894），P=0.015，PFDR=0.074〕，副拟杆菌 属、普雷沃氏菌属9、瘤胃球菌属UCG003组与CH具有潜在关联（P＜0.05，PFDR＞0.10）。且MR-Egger回归、WME、 WM、SM的β值与IVW的β值方向一致。反向MR分析结果显示，CH与放线菌门、粪球菌属1、副拟杆菌属、普雷沃氏 菌属9、瘤胃球菌属UCG003组不存在反向因果关系（P＞0.05）。结论　放线菌门是CH的危险因素，粪球菌属1是CH 的保护因素，副拟杆菌属、普雷沃氏菌属9、瘤胃球菌属UCG003组与CH具有潜在关联。

英文摘要：

Objective To analyze the causal relationship between intestinal flora and cluster headache (CH) by two sample Mendelian randomization (MR) analysis. Methods The intestinal flora dataset was from the MiBioGen consortium, involving 1 053 032 560 single nucleotide polymorphisms (SNPs) . The CH dataset was from the R9 version of the Finnish database, involving 20 167 676 SNPs. In this study, inverse variance weighting (IVW) was used for MR analysis to investigate the potential causal relationship between intestinal flora and CH, and the P value was corrected with false discovery rate (FDR) . Secondly, MR-Egger regression, weighted median estimator (WME) , weighted mode (WM) , and simple mode (SM) were used as supplementary methods for IVW. IVW and MR-Egger regression were used to analyze the reverse causal relationship between intestinal flora and CH. Results IVW analysis results showed that, Actinobacteria was a risk factor for CH [OR=1.786, 95%CI (1.154-2.764) , P=0.009, P FDR=0.046] , Coprococcus 1 was a protective factor for CH [OR=0.563, 95%CI (0.355-0.894) , P=0.015, PFDR=0.074] , Parabacteroides, Prevotella 9 and Ruminococcus UCG003 group were potentially associated with CH (P < 0.05, PFDR > 0.10) . The β values of MR-Egger regression, WME, WM and SM were consistent with the β values of IVW. The results of reverse MR analysis showed that there was no causal relationship between CH and Actinobacteria, Enterococcus 1, Parabacteroides, Prevotella 9, Ruminococcus UCG003 group (P > 0.05) . Conclusion Actinobacteria is a risk factor for CH, Enterococcus 1 is a protective factor for CH, and Parabacteroides, Prevotella 9, Ruminococcus UCG003 group are potentially associated with CH.

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