Repeated sleep disruption in mice leads to persistent shifts in the fecal microbiome and metabolome

• Published in: PloS one Vol. 15; no. 2; p. e0229001
• Main Authors: Bowers, Samuel J, Vargas, Fernando, González, Antonio, He, Shannon, Jiang, Peng, Dorrestein, Pieter C, Knight, Rob, Wright, Jr, Kenneth P, Lowry, Christopher A, Fleshner, Monika, Vitaterna, Martha H, Turek, Fred W
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 20.02.2020; Public Library of Science (PLoS)
• Subjects: Advertising executives; Animal cognition; Animals; Bacteria - classification; Bacteria - genetics; Bacteria - growth & development; Bile acids; Biology; Biology and Life Sciences; Collaboration; Diseases; Disruption; Dysbacteriosis; Experiments; Fecal microflora; Feces; Feces - microbiology; Gastrointestinal Microbiome; Genes; Hydrolase; Hydrolases; Hypotheses; Intestinal microflora; Laboratories; Male; Mass spectrometry; Mass spectroscopy; Medical research; Medicine; Medicine and Health Sciences; Metabolism; Metabolites; Mice; Microbiomes; Microorganisms; Neurobiology; Neurosciences; Pediatrics; Pharmaceutical sciences; Pharmacy; Physical Sciences; Physiology; Protocol; Recovery; Research and Analysis Methods; RNA; RNA, Bacterial - genetics; RNA, Ribosomal, 16S - genetics; rRNA 16S; Scientific imaging; Sleep; Sleep deprivation; Sleep Deprivation - microbiology; Spectroscopy; Taxa; Therapeutic applications; La Jolla California; California; Chicago Illinois; United States > US; Illinois; Colorado
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0229001

It has been established in recent years that the gut microbiome plays a role in health and disease, potentially via alterations in metabolites that influence host physiology. Although sleep disruption and gut dysbiosis have been associated with many of the same diseases, studies investigating the gut microbiome in the context of sleep disruption have yielded inconsistent results, and have not assessed the fecal metabolome. We exposed mice to five days of sleep disruption followed by four days of ad libitum recovery sleep, and assessed the fecal microbiome and fecal metabolome at multiple timepoints using 16S rRNA gene amplicons and untargeted LC-MS/MS mass spectrometry. We found global shifts in both the microbiome and metabolome in the sleep-disrupted group on the second day of recovery sleep, when most sleep parameters had recovered to baseline levels. We observed an increase in the Firmicutes:Bacteroidetes ratio, along with decreases in the genus Lactobacillus, phylum Actinobacteria, and genus Bifidobacterium in sleep-disrupted mice compared to control mice. The latter two taxa remained low at the fourth day post-sleep disruption. We also identified multiple classes of fecal metabolites that were differentially abundant in sleep-disrupted mice, some of which are physiologically relevant and commonly influenced by the microbiome. This included bile acids, and inference of microbial functional gene content suggested reduced levels of the microbial bile salt hydrolase gene in sleep-disrupted mice. Overall, this study adds to the evidence base linking disrupted sleep to the gut microbiome and expands it to the fecal metabolome, identifying sleep disruption-sensitive bacterial taxa and classes of metabolites that may serve as therapeutic targets to improve health after poor sleep.