Table_1_Associations between gut microbiota and sleep: a two-sample, bidirectional Mendelian randomization study.XLSX

IntroductionPrevious research has reported that the gut microbiota performs an essential role in sleep through the microbiome–gut–brain axis. However, the causal association between gut microbiota and sleep remains undetermined.MethodsWe performed a two-sample, bidirectional Mendelian randomization (MR) analysis using genome-wide association study summary data of gut microbiota and self-reported sleep traits from the MiBioGen consortium and UK Biobank to investigate causal relationships between 119 bacterial genera and seven sleep-associated traits. We calculated effect estimates by using the inverse-variance weighted (as the main method), maximum likelihood, simple model, weighted model, weighted median, and MR-Egger methods, whereas heterogeneity and pleiotropy were detected and measured by the MR pleiotropy residual sum and outlier method, Cochran’s Q statistics, and MR-Egger regression.ResultsIn forward MR analysis, inverse-variance weighted estimates concluded that the genetic forecasts of relative abundance of 42 bacterial genera had causal effects on sleep-associated traits. In the reverse MR analysis, sleep-associated traits had a causal effect on 39 bacterial genera, 13 of which overlapped with the bacterial genera in the forward MR analysis.DiscussionIn conclusion, our research indicates that gut microbiota may be involved in the regulation of sleep, and conversely, changes in sleep-associated traits may also alter the abundance of gut microbiota. These findings suggest an underlying reciprocal causal association between gut microbiota and sleep.

引言：既往研究表明，肠道微生物群通过微生物组-肠道-大脑轴在睡眠中发挥着至关重要的作用。然而，肠道微生物群与睡眠之间的因果关联尚未确定。方法：本研究采用双向孟德尔随机化（MR）分析，利用MiBioGen联盟和英国生物样本库提供的全基因组关联研究（GWAS）摘要数据，对肠道微生物群的基因组和自我报告的睡眠特征进行两样本分析，以探究119个细菌属与七个睡眠相关特征之间的因果关系。我们通过逆方差加权（作为主要方法）、最大似然、简单模型、加权模型、加权中位数和MR-Egger方法计算效应估计值，同时利用MR多效性残差和异常值方法、Cochran的Q统计量和MR-Egger回归检测和测量异质性和多效性。结果：在正向MR分析中，逆方差加权估计结果表明，42个细菌属的遗传预测对睡眠相关特征具有因果效应。在反向MR分析中，睡眠相关特征对39个细菌属具有因果效应，其中13个与正向MR分析中的细菌属重叠。讨论：综上所述，本研究表明肠道微生物群可能参与睡眠的调节，反之，睡眠相关特征的变化也可能改变肠道微生物群的丰度。这些发现暗示了肠道微生物群与睡眠之间存在的潜在双向因果关联。