Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Chinese Academy of Medical Sciences Research Unit (No.2018RU006), Peking University, Beijing, China.
National Institute on Drug Dependence and Beijing Key Laboratory of Drug Dependence, Peking University, Beijing, China.
Mol Psychiatry. 2021 Nov;26(11):6277-6292. doi: 10.1038/s41380-021-01113-1. Epub 2021 May 7.
Sleep deprivation (SD) is increasingly common in modern society, which can lead to the dysregulation of inflammatory responses and cognitive impairment, but the mechanisms remain unclear. Emerging evidence suggests that gut microbiota plays a critical role in the pathogenesis and development of inflammatory and psychiatric diseases, possibly via gut microbiota-brain interactions and neuroinflammation. The present study investigated the impact of SD on gut microbiota composition and explored whether alterations of the gut microbiota play a causal role in chronic inflammatory states and cognitive impairment that are induced by SD. We found that SD-induced gut dysbiosis, inflammatory responses, and cognitive impairment in humans. Moreover, the absence of the gut microbiota suppressed inflammatory response and cognitive impairment induced by SD in germ-free (GF) mice. Transplantation of the "SD microbiota" into GF mice activated the Toll-like receptor 4/nuclear factor-κB signaling pathway and impaired cognitive function in the recipient mice. Mice that harbored "SD microbiota" also exhibited increases in neuroinflammation and microglial activity in the hippocampus and medial prefrontal cortex. These findings indicate that gut dysbiosis contributes to both peripheral and central inflammatory processes and cognitive deficits that are induced by SD, which may open avenues for potential interventions that can relieve the detrimental consequences of sleep loss.
睡眠剥夺（SD）在现代社会中越来越普遍，可导致炎症反应失调和认知障碍，但机制尚不清楚。新出现的证据表明，肠道微生物群在炎症性和精神疾病的发病机制和发展中起关键作用，可能通过肠道微生物群-脑相互作用和神经炎症。本研究调查了 SD 对肠道微生物群组成的影响，并探讨了肠道微生物群的改变是否在 SD 诱导的慢性炎症状态和认知障碍中起因果作用。我们发现 SD 可诱导人类肠道菌群失调、炎症反应和认知障碍。此外，无菌（GF）小鼠中缺乏肠道微生物群可抑制 SD 诱导的炎症反应和认知障碍。将“SD 微生物群”移植到 GF 小鼠中可激活 Toll 样受体 4/核因子-κB 信号通路，并损害受体小鼠的认知功能。携带“SD 微生物群”的小鼠还表现出海马体和内侧前额叶皮层中神经炎症和小胶质细胞活性增加。这些发现表明，肠道菌群失调可导致 SD 诱导的外周和中枢炎症过程以及认知缺陷，这可能为缓解睡眠剥夺的有害后果提供潜在干预途径。
