Abstract
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.
Highlights
Emerging evidence suggests that the intestinal microbiota is a source of sleep-promoting signals
Our results demonstrate that oral and intraportal administration of butyrate induces robust increases in non-rapid-eye movement sleep (NREMS), while systemic butyrate treatment has no effect on sleep
In the first four hours after the treatment, time spent in NREMS increased by 47% above baseline at the expense of rapid-eye movement sleep (REMS) and wakefulness (NREMS baseline: 97.9 ± 3.3 min/4 h, tributyrin: 143.7 ± 10.0 min/4 h, p < 0.01; REMS baseline: 6.8 ± 1.0 min/4 h, tributyrin: 0.8 ± 0.3 min/4 h, p < 0.001)
Summary
Emerging evidence suggests that the intestinal microbiota is a source of sleep-promoting signals. Cell wall components of bacteria induce sleep when injected systemically[15,16,17,18] suggesting that fragments of disintegrating intestinal bacteria, once translocated into the portal circulation, could serve in sleep signaling. In addition to the cell wall fragments, live intestinal bacteria are a source of biologically active metabolites, such as short-chain fatty acids (SCFAs), secondary bile acids, indole-derivatives, succinate or hormones and neurotransmitters (reviewed in[19]). Our results demonstrate that oral and intraportal administration of butyrate induces robust increases in non-rapid-eye movement sleep (NREMS), while systemic butyrate treatment has no effect on sleep. These findings indicate the existence of a butyrate-sensitive hepatoportal sleep-inducing sensory mechanism
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
