背景：许多观察性研究已经记录了昼夜节律与肠道微生物群组成之间的关联。然而,早晨时间型对肠道菌群的双向因果效应尚不清楚.
方法：进行了双样本孟德尔随机化研究，使用来自欧洲联盟的早晨型和来自最大可用的全基因组关联研究荟萃分析的肠道微生物群的汇总统计数据，由MiBioGen财团进行。逆方差加权(IVW)，加权模式，加权中位数，MR-Egger回归，和简单的模式方法被用来检查早晨时间型和肠道微生物群之间的因果关系。对肠道微生物群进行了反向孟德尔随机化分析，在最初的孟德尔随机分析中被确定为与早晨时间型有因果关系。Cochran的Q统计量被用来评估工具变量的异质性。
结果：反向方差加权估计表明，早晨时间型对细菌科具有保护作用（β=-0.072；95％CI：-0.143，-0.001；p=0.047），副杆菌属（β=-0.112；95％CI：-0.184，-0.039；p=0.002），和拟杆菌属（β=-0.072；95%CI：-0.143，-0.001；p=0.047）。此外,肠道菌群（拟杆菌科（OR=0.925；95％CI：0.857，0.999；p=0.047），副杆菌属(OR=0.915;95%CI:0.858,0.975;p=0.007),和拟杆菌属（OR=0.925；95％CI：0.857，0.999；p=0.047）对早晨型显示出积极作用。工具变量没有显著的异质性，或者水平多功能性，找到了。
结论：这项孟德尔随机双样本研究发现，副杆菌属,和拟杆菌属与早晨时间型有因果关系。需要进一步的随机对照试验来阐明肠道微生物群对早晨时间型的影响，以及它们的特定保护机制。
BACKGROUND: Numerous observational studies have documented an association between the circadian rhythm and the composition of the gut microbiota. However, the bidirectional causal effect of the morning chronotype on the gut microbiota is unknown.
METHODS: A two-sample Mendelian randomization study was performed, using the summary statistics of the morning chronotype from the European Consortium and those of the gut microbiota from the largest available genome-wide association study meta-analysis, conducted by the MiBioGen consortium. The inverse variance-weighted (IVW), weighted mode, weighted median, MR-Egger regression, and simple mode methods were used to examine the causal association between the morning chronotype and the gut microbiota. A reverse Mendelian randomization analysis was conducted on the gut microbiota, which was identified as causally linked to the morning chronotype in the initial Mendelian randomization analysis. Cochran\'s Q statistics were employed to assess the heterogeneity of the instrumental variables.
RESULTS: Inverse variance-weighted estimates suggested that the morning chronotype had a protective effect on Family Bacteroidaceae (β = -0.072; 95% CI: -0.143, -0.001; p = 0.047), Genus Parabacteroides (β = -0.112; 95% CI: -0.184, -0.039; p = 0.002), and Genus Bacteroides (β = -0.072; 95% CI: -0.143, -0.001; p = 0.047). In addition, the gut microbiota (Family Bacteroidaceae (OR = 0.925; 95% CI: 0.857, 0.999; p = 0.047), Genus Parabacteroides (OR = 0.915; 95% CI: 0.858, 0.975; p = 0.007), and Genus Bacteroides (OR = 0.925; 95% CI: 0.857, 0.999; p = 0.047)) demonstrated positive effects on the morning chronotype. No significant heterogeneity in the instrumental variables, or in horizontal pleiotropy, was found.
CONCLUSIONS: This two-sample Mendelian randomization study found that Family Bacteroidaceae, Genus Parabacteroides, and Genus Bacteroides were causally associated with the morning chronotype. Further randomized controlled trials are needed to clarify the effects of the gut microbiota on the morning chronotype, as well as their specific protective mechanisms.
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