Shi Shangyun, Liu Dongming, Baranova Ancha, Cao Hongbao, Zhang Fuquan
Department of Psychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
Department of Radiology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China.
Gen Psychiatr. 2025 Aug 12;38(4):e101855. doi: 10.1136/gpsych-2024-101855. eCollection 2025.
Although studies in recent years have explored the impact of gut microbiota on various sleep characteristics, the interaction between gut microbiota and insomnia remains unclear.
We aimed to evaluate the mutual influences between gut microbiota and insomnia.
We conducted Mendelian randomisation (MR) analysis using genome-wide association studies datasets on insomnia (N=386 533), gut microbiota data from the MiBioGen alliance (N=18 340) and the Dutch Microbiome Project (N=8208). The inverse variance weighted (IVW) technique was selected as the primary approach. Then, Cochrane's Q, Mendelian randomization-Egger (MR-Egger) and MR Pleiotropy RESidual Sum and Outlier test (MR-PRESSO) tests were used to detect heterogeneity and pleiotropy. The leave-one-out method was used to test the stability of the MR results. In addition, we performed the Steiger test to thoroughly verify the causation.
According to IVW, our results showed that 14 gut bacterial taxa may contribute to the risks of insomnia (odds ratio (OR): 1.01 to 1.04), while 8 gut bacterial taxa displayed a protective effect on this condition (OR: 0.97 to 0.99). Conversely, reverse MR analysis showed that insomnia may causally decrease the abundance of 7 taxa (OR: 0.21 to 0.57) and increase the abundance of 12 taxa (OR: 1.65 to 4.43). Notably, the genus showed a significant positive causal relationship after conducting the Steiger test. Cochrane's Q test indicated no significant heterogeneity between most single-nucleotide polymorphisms. In addition, no significant level of pleiotropy was found according to MR-Egger and MR-PRESSO.
Our study highlighted the reciprocal relationships between gut microbiota and insomnia, which may provide new insights into the treatment and prevention of insomnia.
尽管近年来的研究探讨了肠道微生物群对各种睡眠特征的影响，但肠道微生物群与失眠之间的相互作用仍不清楚。
我们旨在评估肠道微生物群与失眠之间的相互影响。
我们使用全基因组关联研究数据集进行孟德尔随机化（MR）分析，其中失眠数据集（N = 386533）、来自MiBioGen联盟的肠道微生物群数据（N = 18340）以及荷兰微生物组计划（N = 8208）。选择逆方差加权（IVW）技术作为主要方法。然后，使用Cochrane's Q检验、孟德尔随机化Egger（MR-Egger）检验和MR多效性残差总和与异常值检验（MR-PRESSO）来检测异质性和多效性。采用留一法检验MR结果的稳定性。此外，我们进行了Steiger检验以全面验证因果关系。
根据IVW，我们的结果表明，14种肠道细菌分类群可能导致失眠风险增加（优势比（OR）：1.01至1.04），而8种肠道细菌分类群对这种情况具有保护作用（OR：0.97至0.99）。相反，反向MR分析表明，失眠可能会导致7种分类群的丰度下降（OR：0.21至0.57），并使12种分类群的丰度增加（OR：1.65至4.43）。值得注意的是，在进行Steiger检验后，该属显示出显著的正因果关系。Cochrane's Q检验表明大多数单核苷酸多态性之间无显著异质性。此外，根据MR-Egger和MR-PRESSO未发现显著的多效性水平。
我们的研究强调了肠道微生物群与失眠之间的相互关系，这可能为失眠的治疗和预防提供新的见解。
