广州中医药大学吴宝剑课题组宣布他们的研究显示，肠道生物钟通过维持谷氨酰胺平衡来塑造睡眠-觉醒周期。相关论文于2025年11月17日发表在《细胞—代谢》杂志上。

肠道生物钟在传递进食信号和产生昼夜节律事件中发挥作用，但这个生物钟系统如何调节与睡眠-觉醒调节相关的稳态过程尚不清楚。他们对肠上皮细胞（IECs）生物钟的功能解剖表明，维持昼夜睡眠-觉醒周期需要生物钟的完整性。在IECs中，BMAL1产生昼夜节律性的SLC6A19表达，促进肠道在活跃期对谷氨酰胺的吸收，从而增强下丘脑核谷氨酸能神经元的活动，导致觉醒增加和睡眠减少。在休息阶段，谷氨酰胺稳态参与睡眠-觉醒调节也很明显，因为在休息阶段，由REV-ERBα缺乏引起的谷氨酰胺升高与以睡眠减少为特征的睡眠异常密切相关。总的来说，肠道生物钟通过暂时控制谷氨酰胺稳态来塑造昼夜睡眠-觉醒周期，并作为促进睡眠节奏和管理睡眠障碍的潜在目标。

附：英文原文

Title: Intestinal clock shapes sleep-wake cycle via sustaining glutamine homeostasis

Author: Lianxia Guo, Yifei Xiao, Zanjin Li, Yuwei Huang, Haobin Cen, Zicong Wu, Hongbo Wang, Xinyu Liu, Zhehan Yang, Caifeng Zhao, Tingying Hao, Hui Chen, Meng Jin, Danyi Lu, Min Chen, Baojian Wu

Issue&Volume: 2025-11-17

Abstract: The intestinal clock plays a role in transmitting feeding signals and generating circadian events, but how this clock system may time homeostatic processes related to sleep-wake regulation is unknown. Our functional dissections of the circadian clock in intestinal epithelial cells (IECs) demonstrate that its integrity is required for maintenance of the diurnal sleep-wake cycle. In IECs, BMAL1 generates diurnal rhythmic SLC6A19 expression that promotes intestinal absorption of glutamine during the active phase, which enhances glutamatergic neuron activities in hypothalamic nuclei and contributes to increased wakefulness and decreased sleep. The involvement of glutamine homeostasis in sleep-wake regulation is also pronounced during the rest phase, as an elevation of glutamine in the rest phase caused by IEC deficiency of REV-ERBα is causally linked to sleep abnormalities characterized by reduced sleep. Overall, the intestinal clock shapes the diurnal sleep-wake cycle through temporally gating glutamine homeostasis and serves as a potential target for boosting the sleep rhythm and for managing sleep disorders.

DOI: 10.1016/j.cmet.2025.10.010

Source: https://www.cell.com/cell-metabolism/abstract/S1550-4131(25)00444-9