IntroductionSleep deprivation (SD) and obesity are common in modern societies. SD and obesity frequently coexist, but research on the combined consequences of SD and obesity has been limited. In this study, we investigated the gut microbiota and host responses to SD and high-fat diet (HFD)-induced obesity. In addition, we attempted to identify key mediators of the microbiota-gut-brain axis.MethodsC57BL/6J mice were divided into four groups based on whether they were sleep deprived and whether they were fed a standard chow diet (SCD) or HFD. We then performed fecal microbiome shotgun sequencing, gut transcriptome analysis using RNA sequencing, and brain mRNA expression analysis using the nanoString nCounter Mouse Neuroinflammation Panel.ResultsThe gut microbiota was significantly altered by the HFD, whereas the gut transcriptome was primarily influenced by SD. Sleep and diet are both important in the inflammatory system of the brain. When SD and the HFD were combined, the inflammatory system of the brain was severely disrupted. In addition, inosine-5' phosphate may be the gut microbial metabolite that mediates microbiota-gut-brain interactions. To identify the major drivers of this interaction, we analyzed the multi-omics data. Integrative analysis revealed two driver factors that were mostly composed of the gut microbiota. We discovered that the gut microbiota may be the primary driver of microbiota-gut-brain interactions.DiscussionThese findings imply that healing gut dysbiosis may be a viable therapeutic target for enhancing sleep quality and curing obesity-related dysfunction.

Introduction A bi-directional relationship between sleep and neuropathic pain is of interest because of its impact on human health. Numerous studies in humans and animals have examined the association between sleep and neuropathic pain. However, animal studies showed inconsistent results compared to human data. Therefore, validation of an animal model for sleep-pain association research is needed. We examined the animal models to identify a best-fit model predicting sleep disturbances with the level of neuropathic pain. Methods Adult male C57BL/6J mice (n=7 per group) were implanted with electrodes for electroencephalogram (EEG) and electromyogram. After two weeks of recovery, we obtained baseline EEG data for 24 hours and evaluated the paw withdrawal threshold, a measure of pain sensitivity, by the von Frey test. Afterward, sciatic nerve crush injury (SCI) and common peroneal nerve ligation (CPL) were conducted to make the two different neuropathic pain models. Post-surgery sleep was recorded continuously for 24 hours, followed by von Frey tests. EEG recording during the light period and von Frey tests were repeated on post-surgery days 5, 10, and 15. Results Both SCI and CPL models showed lower paw withdrawal thresholds after the peripheral nerve injury. NREM sleep duration on post-surgery day 1 was reduced significantly compared to baseline in both SCI and CPL, but only SCI showed decreased REM sleep. There was a significant positive correlation between paw withdrawal threshold and NREM sleep duration in SCI (P< 0.0001) but not CPL. Also, wake alpha and theta EEG powers were correlated with pain threshold. Conclusion We confirmed that both models of neuropathic pain disturbed sleep patterns. Nevertheless, sleep disturbances were reliably predicted by the pain sensitivity in the SCI model. Hence, we suggest SCI as a reliable pain model for studying the mechanism of sleep-pain association. Support (if any)

Sleep deprivation (SD) and obesity are common in modern societies. SD and obesity frequently coexist, but research on the combined consequences of SD and obesity has been limited. In this study, we investigated the gut microbiota and host responses to SD and high-fat diet (HFD)-induced obesity. In addition, we attempted to identify key mediators of the microbiota-gut-brain axis. C57BL/6J mice were divided into four groups based on whether they were sleep deprived and whether they were fed a standard chow diet (SCD) or HFD. We then performed fecal microbiome shotgun sequencing, gut transcriptome analysis using RNA sequencing, and brain mRNA expression analysis using the nanoString nCounter Mouse Neuroinflammation Panel. The gut microbiota was significantly altered by the HFD, whereas the gut transcriptome was primarily influenced by SD. Sleep and diet are both important in the inflammatory system of the brain. When SD and the HFD were combined, the inflammatory system of the brain was severely disrupted. In addition, inosine-5' phosphate may be the gut microbial metabolite that mediates microbiota-gut-brain interactions. To identify the major drivers of this interaction, we analyzed the multi-omics data. Integrative analysis revealed two driver factors that were mostly composed of the gut microbiota. We discovered that the gut microbiota may be the primary driver of microbiota-gut-brain interactions. These findings imply that healing gut dysbiosis may be a viable therapeutic target for enhancing sleep quality and curing obesity-related dysfunction.