研究发现肠道菌群与睡眠的调节密切相关，但肠道菌群在失眠障碍中的病理生理机制目前国内外均未见相关研究报道。我们的预实验结果显示失眠障碍患者存在肠道菌群紊乱，且拟杆菌门、梭菌目和罗氏菌属是区分正常人群和失眠障碍患者的3个关键菌种，且与快速眼动（REM）睡眠密切相关。另有研究表明，梭菌目和罗氏菌属能分泌β-羟丁酸并可选择性作用于脑源性神经营养因子（BDNF）生成。BDNF与TrkB结合后能促进神经递质的释放，激活细胞内信号传导通路，调控GABA能神经元的传递。同时，脑干中BDNF可调控REM期睡眠稳定性。本研究拟在此基础上，从大样本量临床随访研究中进一步证实肠道菌群及其代谢产物与失眠障碍发生、发展的联系；同时，通过肠道菌群移植和代谢产物干扰等动物实验进一步探讨肠道菌群及其代谢产物在失眠障碍中的分子调控机制。此研究能够为肠道菌群精准靶向治疗失眠障碍提供理论和实践依据。

Increasing evidence has shown that gut microbiota are closely associated with sleep-wake regulation. However, the molecular mechanism of gut microbiota on insomnia disorder remains unknown. Our preliminary studies have shown that gut microbiota homeostasis is the key factor associated with insomnia disorder, especially Bacteroides, Clostridiales, and Roseburia, which are three key microbiota to distinguish the healthy population and patients with insomnia disorder and closely associated with the REM sleep stability. Recent studies have shown that β-hydroxybutyrate from Clostridiales and Roseburia could selectively affect the BDNF production. BDNF interacting with TrkB promote neurotransmitter releases, activate the intracellular signaling pathway and regulates the activity GABAergic neuron. Meanwhile, BDNF could regulates REM sleep stability. In present study, we sought to take further step to investigate the relationship between gut microbiota and the metabolites on the development and progression of insomnia disorder. Furthermore, the molecular mechanisms of insomnia disorder will be further explored by investigating the microbiota transplantation and metabolites supplementation on experimental mice. The current attempt will provide clinical and therapeutic strategies for the treatment of insomnia disorder.