Gut microbiota modulates the inflammatory response and cognitive impairment induced by sleep deprivation
Gut microbiota modulates the inflammatory response and cognitive impairment induced by sleep deprivation
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肠道微生物群调节睡眠剥夺引起的炎症反应和认知障碍。
DOI：
10.1038/s41380-021-01113-1
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发表时间：
2021-05-07
影响因子：
11
通讯作者：
Han, Ying
中科院分区：
文献类型：
--
作者：
Wang, Zhong;Chen, Wen-Hao;Han, Ying
睡眠剥夺（SD）在现代社会越来越普遍，这可能导致炎症反应失调和认知障碍，但其机制仍不清楚。新的证据表明，肠道微生物群可能通过肠道微生物群与大脑的相互作用和神经炎症，在炎症和精神疾病的发病机制和发展中发挥着关键作用。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 引起的慢性炎症状态和认知障碍中起因果作用。我们发现 SD 会引起人类肠道菌群失调、炎症反应和认知障碍。此外，肠道微生物群的缺失抑制了无菌 (GF) 小鼠由 SD 引起的炎症反应和认知障碍。将“SD微生物群”移植到GF小鼠体内会激活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皮质的神经炎症和小胶质细胞活性增加。这些发现表明，肠道菌群失调会导致 SD 引起的外周和中枢炎症过程以及认知缺陷，这可能为潜在的干预措施开辟途径，减轻睡眠不足的有害后果。
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-kappa B 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.