Zhang Yingying, Zhou Siyu, Han Hanghang, Du Xueke
Department of Anesthesiology, The Second Affiliated Hospital of Guangxi Medical University, Nanning 530007, Guangxi Zhuang Autonomous Region, China.
Department of Anesthesiology, The Second Affiliated Hospital of Guangxi Medical University, Nanning 530007, Guangxi Zhuang Autonomous Region, China.
J Affect Disord. 2025 Apr 1;374:350-355. doi: 10.1016/j.jad.2024.12.104. Epub 2025 Jan 11.
Research has suggested an interaction between gut microbiota and sleep, yet the causal relationships between gut microbiota, metabolites, and sleep disorders remain unclear. This study aims to uncover these relationships.
We obtained genome-wide data for 196 gut microbiota (GM) species (N = 18,340), 1,400 metabolites (N = 8,299), and sleep disorders (N = 361,194). Mendelian randomization(MR) analyses were conducted using the Inverse Variance Weighted (IVW) method, MR-Egger, Weighted Median method, Weighted Mode method, and Simple Mode method to infer causality. The IVW method was used for primary analysis results. Significant microbiota and causal metabolites were further analyzed to clarify the associations between the three. All results were tested for heterogeneity, pleiotropy, and sensitivity to assess the stability of the findings.
The Mendelian randomization results revealed causal relationships between four gut microbiota species and sleep disorders: Genus.Dorea, Genus.Parasutterell, Genus.Slackia, and Order.Bacillales. Additionally, we identified 39 causal metabolites Related to sleep disorders, with 7 of these being associated with 3 causal microbiota species at the genus level. All results showed no heterogeneity or horizontal pleiotropy.
Through two-sample Mendelian randomization studies, we identified three gut microbiota species at the genus level genetically linked to sleep disorders through seven plasma metabolites, revealing causal relationships between these three factors. These biomarkers provide new insights into the mechanisms of sleep disorders and may contribute to their prevention, diagnosis, and treatment.
研究表明肠道微生物群与睡眠之间存在相互作用，但肠道微生物群、代谢产物和睡眠障碍之间的因果关系仍不清楚。本研究旨在揭示这些关系。
我们获取了196种肠道微生物群（GM）物种（N = 18,340）、1400种代谢产物（N = 8,299）和睡眠障碍（N = 361,194）的全基因组数据。使用逆方差加权（IVW）方法、MR-Egger、加权中位数方法、加权模式方法和简单模式方法进行孟德尔随机化（MR）分析以推断因果关系。IVW方法用于主要分析结果。对显著的微生物群和因果代谢产物进行进一步分析，以阐明三者之间的关联。对所有结果进行异质性、多效性和敏感性检验，以评估研究结果的稳定性。
孟德尔随机化结果揭示了四种肠道微生物群物种与睡眠障碍之间的因果关系：多雷亚属、副萨特氏菌属、斯拉基菌属和芽孢杆菌目。此外，我们确定了39种与睡眠障碍相关的因果代谢产物，其中7种在属水平上与3种因果微生物群物种相关。所有结果均未显示异质性或水平多效性。
通过两样本孟德尔随机化研究，我们在属水平上确定了三种肠道微生物群物种，它们通过七种血浆代谢产物与睡眠障碍存在遗传联系，揭示了这三个因素之间的因果关系。这些生物标志物为睡眠障碍的机制提供了新的见解，并可能有助于其预防、诊断和治疗。
