Butyrate, a metabolite of intestinal bacteria, enhances sleep

Butyrate, a metabolite of intestinal bacteria, enhances sleep Éva Szentirmai 1 2, Nicklaus S Millican 3, Ashley R Massie 3, Levente Kapás 3 4 Affiliations expand PMID: 31065013 PMCID: PMC6504874 DOI: 10.1038/s41598-019-43502-1 Free PMC article 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. Conflict of interest statement The authors declare no competing interests. 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Rep. 2017;7:958. doi: 10.1038/s41598-017-01047-1. - DOI - PMC - PubMed Show all 64 references Publication types Research Support, N.I.H., Extramural MeSH terms Administration, Oral Animals Butyrates / administration & dosage Butyrates / metabolism Butyrates / pharmacology* Butyric Acid / administration & dosage Butyric Acid / pharmacology Gastrointestinal Microbiome / physiology* Injections Mice, Inbred C57BL Rats, Sprague-Dawley Sleep / drug effects* Sleep / physiology* Triglycerides / administration & dosage Triglycerides / pharmacology Substances Butyrates Triglycerides Butyric Acid tributyrin Related information MedGen PubChem Compound (MeSH Keyword) Grant support R01 HL122390/HL/NHLBI NIH HHS/United States LinkOut - more resources Full Text Sources Europe PubMed Central Nature Publishing Group PubMed Central