Elson S. Floyd College of Medicine, Department of Biomedical Sciences, Washington State University, Spokane, Washington, United States of America.
Sleep and Performance Research Center, Washington State University, Spokane, Washington, United States of America.
Sci Rep. 2019 May 7;9(1):7035. doi: 10.1038/s41598-019-43502-1.
Emerging evidence suggests that the intestinal microbiota is a source of sleep-promoting signals. Bacterial metabolites and components of the bacterial cell wall are likely to provide important links between the intestinal commensal flora and sleep-generating mechanisms in the brain. Butyrate is a short-chain fatty acid produced by the intestinal bacteria by the fermentation of nondigestible polysaccharides. We tested the hypothesis that butyrate may serve as a bacterial-derived sleep-promoting signal. Oral gavage administration of tributyrin, a butyrate pro-drug, elicited an almost 50% increase in non-rapid-eye movement sleep (NREMS) in mice for 4 hours after the treatment. Similarly, intraportal injection of butyrate led to prompt and robust increases in NREMS in rats. In the first 6 hours after the butyrate injection, NREMS increased by 70%. Both the oral and intraportal administration of butyrate led to a significant drop in body temperature. Systemic subcutaneous or intraperitoneal injection of butyrate did not have any significant effect on sleep or body temperature. The results suggest that the sleep-inducing effects of butyrate are mediated by a sensory mechanism located in the liver and/or in the portal vein wall. Hepatoportal butyrate-sensitive mechanisms may play a role in sleep modulation by the intestinal microbiota.
新出现的证据表明，肠道微生物群是促进睡眠的信号源。细菌代谢物和细菌细胞壁的组成部分可能为肠道共生菌群与大脑中产生睡眠的机制之间提供重要联系。丁酸是肠道细菌通过发酵不可消化的多糖产生的短链脂肪酸。我们检验了丁酸可能作为细菌来源的促睡眠信号的假说。丁三酯，一种丁酸前体药物，经口灌胃给药后，在治疗后 4 小时内可使小鼠的非快速眼动睡眠（NREMS）增加近 50%。同样，门静脉内注射丁酸可使大鼠的 NREMS 迅速而强烈地增加。在丁酸注射后的头 6 小时内，NREMS 增加了 70%。丁酸的口服和门静脉内给药均导致体温明显下降。丁酸的全身皮下或腹腔内注射对睡眠或体温没有任何显著影响。结果表明，丁酸的催眠作用是通过位于肝脏和/或门静脉壁中的感觉机制介导的。肠道微生物群对睡眠的调节可能涉及肝门丁酸敏感机制。
