通讯作者: 华琳, hualin7750@139.com

DOI：10.12201/bmr.202409.00006

Identification of links between sleepiness and gut microbiota using Mendelian randomization analysis

• 摘要：目的 白天嗜睡可由多种原因引起，如阻塞性睡眠呼吸暂停（obstructive sleep apnea, OSA）、失眠、睡眠卫生不良等，然而只有约一半的OSA患者主诉白天嗜睡，此外，在经过充分的睡眠和有效的治疗OSA后有小部分患者仍有白天嗜睡的症状。造成嗜睡的原因以及在人群中差异性表现的确切原因尚不清楚。众多的证据表明肠道微生物群与睡眠疾病和觉醒状态密切相关。本研究将探讨白天嗜睡人群的肠道菌群有何变化特点，为深入认识嗜睡原因提供参考。方法 利用全基因组关联研究（genome-wide association study，GWAS）数据，进行两样本的孟德尔随机化（Mendelian randomization, MR）分析，将肠道菌群作为暴露因素，嗜睡作为结局因素，以单核苷酸多态性（single nucleotide polymorphisms, SNPs）作为工具变量，使用逆方差加权法来筛查白天嗜睡的潜在致病肠道微生物。通过使用不同的敏感性分析，确保MR分析结果的稳健性。结果 综合多重分析结果，发现丁酸单胞菌(Butyricimonas)、消化球菌(Peptococcus)、嗜胆菌(Bilophila)、厌氧菌(Anaerofilum)、瘤胃球菌(Ruminococcusgnavus)和粪球菌(Coprococcus)在嗜睡人群中丰度相对较高，而颤螺旋菌(Oscillospira)和脱硫弧菌(Desulfovibrio)丰度相对较低。 结论 本研究结果表明嗜睡人群存在肠道菌群失调，通过采取措施（如饮食结构的改变、益生菌的使用等）对肠道菌群结构的调整，是否成为改善白天嗜睡的新方法，有待于今后进一步研究证实。

  关键词： 嗜睡; 肠道菌群; 微生物群-肠道-大脑轴; 单核苷酸多态性; 孟德尔随机化

   

  Abstract: Objective Daytime sleepiness can be caused by a variety of reasons, such as sleep apnea (OSA), insomnia, poor sleep hygiene, etc. However, only about half of OSA patients complain of daytime sleepiness. In addition, after adequate sleep and effective treatment of OSA, a small number of patients still have symptoms of daytime sleepiness. The exact reasons for sleepiness and differences in the population are not clear. Numerous evidences have shown that the gut microbiota is closely associated with sleep disorders and waikefulness. This study will investigate whether there is an association between daytime sleepiness and gut microbiota, and provide a refence for further understanding of sleepiness. Methods Two-sample Mendelian randomization (Mr) analysis was performed using genome-wide association study (GWAS) data, with gut microbiota as an exposure factor, sleepiness as an outcome factor, and single nucleotide polymorphisms (SNPs) as an instrumental variable, and inverse variance weighting (IVW) was used to screen potential pathogenic gut microbes for daytime sleepiness. The robustness of the results of the Mr analysis was ensured by using different sensitivity analyses. Results Based on the results of the multiple analyses, Butyricimonas, Peptococcus, Bilophila, Anaerofilum, Ruminococcus gnavus and Coprococcus were relatively abundant in the sleepiness population, while Oscillospira and Desulfovibrio were relatively less abundant. Conclusion The results of this study indicated that there was an imbalance of gut microbiota in sleepiness people. Whether the adjustment of intestinal flora structure by taking measures (such as the change of dietary structure, the use of probiotics, etc.) Is a new way to improve daytime sleepiness remains to be confirmed by further studies in the future.

  Key words: Daytime sleepiness; Gut microbiota; Microbiota-gut-brain axis; Single Nucleotide Polymorphisms (SNP); Mendelian randomization

  提交时间：2024-09-03

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• 序号	提交日期	编号	操作
  1	2024-07-10	bmr.202409.00006V1	下载

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