Wu Jun, Zhang Baofu, Zhou Shengjie, Huang Ziyi, Xu Yindong, Lu Xinwu, Zheng Xiangtao, Ouyang Dong
Department of Vascular Surgery, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Department of Obstetrics and Gynecology, Taizhou Women and Children's Hospital of Wenzhou Medical University, Taizhou, Zhejiang, China.
Front Microbiol. 2023 Aug 14;14:1236847. doi: 10.3389/fmicb.2023.1236847. eCollection 2023.
Previous 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.
We 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.
In 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.
In 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.
先前的研究报告称，肠道微生物群通过微生物-肠道-脑轴在睡眠中发挥重要作用。然而，肠道微生物群与睡眠之间的因果关系仍未确定。
我们使用来自MiBioGen联盟和英国生物银行的肠道微生物群全基因组关联研究汇总数据以及自我报告的睡眠特征进行了两样本双向孟德尔随机化（MR）分析，以研究119个细菌属与七个睡眠相关特征之间的因果关系。我们使用逆方差加权法（作为主要方法）、最大似然法、简单模型、加权模型、加权中位数法和MR-Egger法计算效应估计值，而通过MR多效性残差和离群值法、 Cochr an's Q统计量和MR-Egger回归检测和测量异质性和多效性。
在前向MR分析中，逆方差加权估计得出结论，42个细菌属相对丰度的遗传预测对睡眠相关特征有因果效应。在反向MR分析中，睡眠相关特征对39个细菌属有因果效应，其中13个与前向MR分析中的细菌属重叠。
总之，我们的研究表明肠道微生物群可能参与睡眠调节，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。这些发现提示了肠道微生物群与睡眠之间潜在的相互因果关系。
