Zheng Feng, Liu Shuai, Wei Tian, Wang Lei, Chang Yuanyuan, Qu Hao, Zheng Lei
School of Food and Biological Engineering, Hefei University of Technology, Hefei, China.
Department of Toxicology, School of Public Health, Anhui Medical University, Hefei, China.
Sci Adv. 2025 Jul 18;11(29):eadr8592. doi: 10.1126/sciadv.adr8592.
Prolonged sleep deprivation (SD) results in increased accumulation of reactive oxygen species (ROS) in gut, although the underlying mechanisms remain to be elucidated. This study identifies d-serine as a crucial regulator of gut ROS during SD. Knockdown of serine racemase (SR), the enzyme responsible for d-serine production, prevents the enhanced ROS buildup during SD in . Gut enterocytes (ECs) respond to γ-aminobutyric acid (GABA) signaling by producing d-serine, which influences downstream -methyl-d-aspartate receptor (NMDAR) activity and modulates sleep pressure. However, the continuous demand for sleep disrupts this feedback loop. Prolonged SD leads to increased levels of d-serine in the gut, an elevated pyruvate pool in ECs, enhanced mitochondrial oxidative phosphorylation, impaired lipid metabolism in peroxisomes, and the accumulation of harmful ROS. In conclusion, our findings illuminate the metabolic alterations and brain-gut communication pathways that may contribute to the increase in gut d-serine and subsequent ROS accumulation induced by SD.
长期睡眠剥夺（SD）会导致肠道中活性氧（ROS）的积累增加，尽管其潜在机制仍有待阐明。本研究确定d-丝氨酸是睡眠剥夺期间肠道ROS的关键调节因子。敲低负责产生d-丝氨酸的丝氨酸消旋酶（SR），可防止睡眠剥夺期间肠道中ROS的增强积累。肠道肠上皮细胞（ECs）通过产生d-丝氨酸对γ-氨基丁酸（GABA）信号作出反应，d-丝氨酸会影响下游N-甲基-D-天冬氨酸受体（NMDAR）的活性并调节睡眠压力。然而，对睡眠的持续需求会破坏这一反馈回路。长期睡眠剥夺会导致肠道中d-丝氨酸水平升高、肠上皮细胞中丙酮酸池增加、线粒体氧化磷酸化增强、过氧化物酶体中脂质代谢受损以及有害ROS的积累。总之，我们的研究结果揭示了可能导致睡眠剥夺引起肠道d-丝氨酸增加和随后ROS积累的代谢改变和脑-肠通讯途径。
