Li Peihong, Wang Song, Li Jiaxin, Xiao Zheng, Zhu Haoyue, Sheng Dandan, Liu Weiping, Xiao Bo, Zhou Luo
Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Am J Med Genet B Neuropsychiatr Genet. 2025 Jun;198(4):e33021. doi: 10.1002/ajmg.b.33021. Epub 2025 Jan 3.
BackgroundInsomnia is a common neurological disorder that exhibits connections with the gut microbiota; however, the exact causal relationship remains unclear. MethodsWe conducted a Mendelian randomization (MR) study to systematically evaluate the causal effects of genus-level gut microbiota on insomnia risk in individuals of European ancestry. Summary-level datasets on gut microbiota were sourced from the genome-wide association study (GWAS) of MiBioGen, while datasets on insomnia were obtained from the GWAS of Neale Lab and FinnGen. The primary analytical approach used was the inverse-variance weighted (IVW) method, supplemented by MR-Egger, maximum likelihood, MR-robust adjusted profile score, and weighted median. Sensitivity analyses were conducted to ensure robustness. ResultsThe microbial taxa Enterorhabdus, Family XIII AD3011 group, Paraprevotella, and Lachnospiraceae UCG004 were associated with an increased risk of insomnia, whereas Coprococcus1, Coprobacter, Desulfovibrio, Flavonifractor, Olsenella, Odoribacter, and Oscillibacter were linked to a decreased risk. Regarding the insomnia phenotype characterized by trouble falling asleep, the microbial taxon Eisenbergiella was correlated with an increased risk, while Haemophilus and the Eubacterium brachy group were associated with a reduced risk. Furthermore, for the insomnia phenotype characterized by waking too early, the microbial taxa Family XIII UCG001, Lachnospiraceae FCS020 group, and Olsenella were linked to an increased risk, whereas the Eubacterium brachy group and Victivallis were associated with a lower risk. The results remained robust across all sensitivity analyses. ConclusionOur MR study identified multiple genus-level gut microbial taxa that may exhibit potential causal effects on insomnia from a genetic perspective. These findings provide evidence supporting the theory of the microbiota-gut-brain axis and offer new insights into potential prevention and therapeutic targets for insomnia.
背景
失眠是一种常见的神经系统疾病，与肠道微生物群存在关联；然而，确切的因果关系仍不明确。
方法
我们进行了一项孟德尔随机化（MR）研究，以系统评估欧洲血统个体中属水平肠道微生物群对失眠风险的因果效应。肠道微生物群的汇总水平数据集来自MiBioGen的全基因组关联研究（GWAS），而失眠数据集则取自Neale实验室和FinnGen的GWAS。使用的主要分析方法是逆方差加权（IVW）法，并辅以MR-Egger、最大似然法、MR稳健调整轮廓得分法和加权中位数法。进行敏感性分析以确保结果的稳健性。
结果
肠道微生物分类群Enterorhabdus、XIII AD3011科组、副普雷沃菌属和毛螺菌科UCG004与失眠风险增加相关，而粪球菌属1、粪杆菌属、脱硫弧菌属、黄酮分解菌属、奥尔森菌属、气味杆菌属和颤杆菌属与风险降低相关。对于以入睡困难为特征的失眠表型，肠道微生物分类群艾氏菌属与风险增加相关，而嗜血杆菌属和短真杆菌组与风险降低相关。此外，对于以早醒为特征的失眠表型，肠道微生物分类群XIII UCG001科、毛螺菌科FCS020组和奥尔森菌属与风险增加相关，而短真杆菌组和Victivallis与风险降低相关。所有敏感性分析的结果均保持稳健。
结论
我们的MR研究从遗传学角度确定了多个可能对失眠具有潜在因果效应的属水平肠道微生物分类群。这些发现为微生物群-肠-脑轴理论提供了证据支持，并为失眠的潜在预防和治疗靶点提供了新的见解。
