Causal Effects of Gut Microbiota on Sleep-Related Phenotypes: A Two-Sample Mendelian Randomization Study.

IF 2.1 Q3 CLINICAL NEUROLOGY
Min Yue, Chuandi Jin, Xin Jiang, Xinxin Xue, Nan Wu, Ziyun Li, Lei Zhang
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引用次数: 1

Abstract

Increasing evidence suggests a correlation between changes in the composition of gut microbiota and sleep-related phenotypes. However, it remains uncertain whether these associations indicate a causal relationship. The genome-wide association study summary statistics data of gut microbiota (n = 18,340) was downloaded from the MiBioGen consortium and the data of sleep-related phenotypes were derived from the UK Biobank, the Medical Research Council-Integrative Epidemiology Unit, Jones SE, the FinnGen consortium. To test and estimate the causal effect of gut microbiota on sleep traits, a two-sample Mendelian randomization (MR) approach using multiple methods was conducted. A series of sensitive analyses, such as horizontal pleiotropy analysis, heterogeneity test, MR Steiger directionality test and "leave-one-out" analysis as well as reverse MR analysis, were conducted to assess the robustness of MR results. The genus Anaerofilum has a negative causal effect on getting up in the morning (odd ratio = 0.977, 95% confidence interval: 0.965-0.988, p = 7.28 × 10-5). A higher abundance of order Enterobacteriales and family Enterobacteriaceae contributed to becoming an "evening person". Six and two taxa were causally associated with longer and shorter sleep duration, respectively. Specifically, two SCFA-produced genera including Lachnospiraceae UCG004 (odd ratio = 1.029, 95% confidence interval = 1.012-1.046, p = 6.11 × 10-4) and Odoribacter contribute to extending sleep duration. Two obesity-related genera such as Ruminococcus torques (odd ratio = 1.024, 95% confidence interval: 1.011-1.036, p = 1.74 × 10-4) and Senegalimassilia were found to be increased and decreased risk of snoring, respectively. In addition, we found two risk taxa of insomnia such as the order Selenomonadales and one of its classes called Negativicutes. All of the sensitive analysis and reverse MR analysis results indicated that our MR results were robust. Our study revealed the causal effect of gut microbiota on sleep and identified causal risk and protective taxa for chronotype, sleep duration, snoring and insomnia, which has the potential to provide new perspectives for future mechanistic and clinical investigations of microbiota-mediated sleep abnormal patterns and provide clues for developing potential microbiota-based intervention strategies for sleep-related conditions.

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肠道微生物群对睡眠相关表型的因果影响:一项两样本孟德尔随机化研究。
越来越多的证据表明,肠道微生物群组成的变化与睡眠相关表型之间存在相关性。然而,目前尚不确定这些关联是否表明存在因果关系。肠道微生物群(n=18340)的全基因组关联研究汇总统计数据从MiBioGen联盟下载,睡眠相关表型数据来自英国生物库、医学研究委员会综合流行病学部门、Jones SE和FinnGen联盟。为了测试和估计肠道微生物群对睡眠特征的因果影响,使用多种方法进行了两样本孟德尔随机化(MR)方法。进行了一系列敏感分析,如水平多效性分析、异质性测试、MR Steiger方向性测试和“漏一”分析以及反向MR分析,以评估MR结果的稳健性。Anaerofilum属对早晨起床具有负因果效应(奇数比=0.977,95%置信区间:0.965-0.988,p=7.28×10-5)。肠杆菌目和肠杆菌科的丰度较高有助于成为“夜猫子”。六个和两个分类群分别与较长和较短的睡眠时间有因果关系。具体而言,两个产生SCFA的属,包括Lachnospiraceae UCG004(奇数比=1.029,95%置信区间=1.012-1.046,p=6.11×10-4)和气味杆菌,有助于延长睡眠时间。两个与肥胖相关的属,如Ruminococcus torques(奇数比=1.024,95%置信区间:1.011-1.036,p=1.74×10-4)和Senegalisalia,分别增加和降低打鼾的风险。此外,我们还发现了两个失眠的风险分类群,如Selenomonadales目和其中一个名为负性门的分类群。所有的敏感性分析和反向MR分析结果都表明我们的MR结果是稳健的。我们的研究揭示了肠道微生物群对睡眠的因果影响,并确定了时间类型、睡眠持续时间、打鼾和失眠的因果风险和保护分类群,这有可能为微生物群介导的睡眠异常模式的未来机制和临床研究提供新的视角,并为开发潜在的基于微生物群的睡眠相关疾病干预策略提供线索。
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来源期刊
Clocks & Sleep
Clocks & Sleep Multiple-
CiteScore
4.40
自引率
0.00%
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审稿时长
7 weeks
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