Data_Sheet_1_Associations between gut microbiota and sleep: a two-sample, bidirectional Mendelian randomization study.docx

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：既往研究指出，肠道微生物群通过微生物组-肠道-大脑轴在睡眠过程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得到明确界定。
方法：本研究采用双向孟德尔随机化（MR）分析，利用来自MiBioGen联盟和UK Biobank的肠道微生物群全基因组关联研究汇总数据和自报睡眠特征，旨在探究119种细菌属与七种与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，而异质性和多效性则通过MR多效性残差总和及异常值方法、Cochran的Q统计量和MR-Egger回归进行检测和测量。
结果：在正向MR分析中，逆方差加权估计结果表明，42种细菌属的遗传预测相对丰度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种细菌属具有因果效应，其中13种与正向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潜在的相互因果关联。