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Sleep disruption is a challenging and exceedingly common physiological state that contributes to a wide range of biochemical and molecular perturbations and has been linked to numerous adverse health outcomes. Modern society exerts significant pressure on the sleep/wake cycle via myriad factors, including exposure to electric light, psychological stressors, technological interconnection, jet travel, shift work, and widespread use of sleep-affecting compounds. Interestingly, recent research has identified a link between the microbiome and the regulation of sleep, suggesting that interventions targeting the microbiome may offer unique therapeutic approaches to challenges posed by sleep disruption. In this study, we test the hypothesis that administration of a prebiotic diet containing galactooligosaccharides (GOS) and polydextrose (PDX) in adult male rats improves sleep in response to repeated sleep disruption and during recovery sleep. We found that animals fed the GOS/PDX prebiotic diet for 4 weeks exhibit increased non-rapid eye movement (NREM) and rapid eye movement (REM) sleep during 5 days of sleep disruption and increased total sleep time during 24 h of recovery from sleep disruption compared to animals fed a control diet, despite similar baseline sleep characteristics. Further, the GOS/PDX prebiotic diet led to significant changes in the fecal microbiome. Consistent with previous reports, the prebiotic diet increased the relative abundance of the species Parabacteroides distasonis, which positively correlated with sleep parameters during recovery sleep. Taken together, these findings suggest that the GOS/PDX prebiotic diet may offer an approach to improve resilience to the physiologic challenge of sleep disruption, in part through impacts on the microbiome.

Sleep disruption is a challenging and exceedingly common physiological state that contributes to a wide range of biochemical and molecular perturbations and has been linked to numerous adverse health outcomes. Modern society exerts significant pressure on the sleep/wake cycle via myriad factors, including exposure to electric light, psychological stressors, technological interconnection, jet travel, shift work, and widespread use of sleep-affecting compounds. Interestingly, recent research has identified a link between the microbiome and the regulation of sleep, suggesting that interventions targeting the microbiome may offer unique therapeutic approaches to challenges posed by sleep disruption. In this study, we test the hypothesis that administration of a prebiotic diet containing galactooligosaccharides (GOS) and polydextrose (PDX) in adult male rats improves sleep in response to repeated sleep disruption and during recovery sleep. We found that animals fed the GOS/PDX prebiotic diet for 4 weeks exhibit increased non-rapid eye movement (NREM) and rapid eye movement (REM) sleep during 5 days of sleep disruption and increased total sleep time during 24 h of recovery from sleep disruption compared to animals fed a control diet, despite similar baseline sleep characteristics. Further, the GOS/PDX prebiotic diet led to significant changes in the fecal microbiome. Consistent with previous reports, the prebiotic diet increased the relative abundance of the species Parabacteroides distasonis, which positively correlated with sleep parameters during recovery sleep. Taken together, these findings suggest that the GOS/PDX prebiotic diet may offer an approach to improve resilience to the physiologic challenge of sleep disruption, in part through impacts on the microbiome.

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.

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.

Determine stability of individual differences in executive function, cognitive processing speed, selective visual attention, and maintenance of wakefulness during simulated sustained operations with combined sleep restriction and circadian misalignment. Twenty healthy adults (eight female), aged 25.7 (±4.2 SD), body mass index (BMI) 22.3 (±2.1) kg/m2 completed an 18-day protocol twice. Participants maintained habitual self-selected 8-hour sleep schedules for 2 weeks at home prior to a 4-day laboratory visit that included one sleep opportunity per day: 8 hours on night 1, 3 hours on night 2, and 3 hours on mornings 3 and 4. After 3 days of unscheduled sleep at home, participants repeated the entire protocol. Stability and task dependency of individual differences in performance were quantified by intra-class correlation coefficients (ICC) and Kendall's Tau, respectively. Performance on Stroop, Visual Search, and the Maintenance of Wakefulness Test were highly consistent within individuals during combined sleep restriction and circadian misalignment. Individual differences were trait-like as indicated by ICCs (0.54-0.96) classified according to standard criteria as moderate to almost perfect. Individual differences on other performance tasks commonly reported in sleep studies showed fair to almost perfect ICCs (0.22-0.94). Kendall's rank correlations showed that individual vulnerability to sleep restriction and circadian misalignment varied by task and by metric within a task. Consistent vulnerability of higher-order cognition and maintenance of wakefulness to combined sleep restriction and circadian misalignment has implications for the development of precision countermeasure strategies for workers performing safety-critical tasks, e.g. military, police, health care workers and emergency responders.

To understand the health impact of long-duration spaceflight, one identical twin astronaut was monitored before, during, and after a 1-year mission onboard the International Space Station; his twin served as a genetically matched ground control. Longitudinal assessments identified spaceflight-specific changes, including decreased body mass, telomere elongation, genome instability, carotid artery distension and increased intima-media thickness, altered ocular structure, transcriptional and metabolic changes, DNA methylation changes in immune and oxidative stress-related pathways, gastrointestinal microbiota alterations, and some cognitive decline postflight. Although average telomere length, global gene expression, and microbiome changes returned to near preflight levels within 6 months after return to Earth, increased numbers of short telomeres were observed and expression of some genes was still disrupted. These multiomic, molecular, physiological, and behavioral datasets provide a valuable roadmap of the putative health risks for future human spaceflight.

The invention of electric light has facilitated a society in which people work, sleep, eat, and play at all hours of the 24-hour day. Although electric light clearly has benefited humankind, exposures to electric light, especially light at night (LAN), may disrupt sleep and biological processes controlled by endogenous circadian clocks, potentially resulting in adverse health outcomes. Many of the studies evaluating adverse health effects have been conducted among night- and rotating-shift workers, because this scenario gives rise to significant exposure to LAN. Because of the complexity of this topic, the National Toxicology Program convened an expert panel at a public workshop entitled "Shift Work at Night, Artificial Light at Night, and Circadian Disruption" to obtain input on conducting literature-based health hazard assessments and to identify data gaps and research needs. The Panel suggested describing light both as a direct effector of endogenous circadian clocks and rhythms and as an enabler of additional activities or behaviors that may lead to circadian disruption, such as night-shift work and atypical and inconsistent sleep-wake patterns that can lead to social jet lag. Future studies should more comprehensively characterize and measure the relevant light-related exposures and link these exposures to both time-independent biomarkers of circadian disruption and biomarkers of adverse health outcomes. This information should lead to improvements in human epidemiological and animal or in vitro models, more rigorous health hazard assessments, and intervention strategies to minimize the occurrence of adverse health outcomes due to these exposures.

The invention of electric light has facilitated a society in which people work, sleep, eat, and play at all hours of the 24-hour day. Although electric light clearly has benefited humankind, exposures to electric light, especially light at night (LAN), may disrupt sleep and biological processes controlled by endogenous circadian clocks, potentially resulting in adverse health outcomes. Many of the studies evaluating adverse health effects have been conducted among night- and rotating-shift workers, because this scenario gives rise to significant exposure to LAN. Because of the complexity of this topic, the National Toxicology Program convened an expert panel at a public workshop entitled “Shift Work at Night, Artificial Light at Night, and Circadian Disruption” to obtain input on conducting literature-based health hazard assessments and to identify data gaps and research needs. The Panel suggested describing light both as a direct effector of endogenous circadian clocks and rhythms and as an enabler of additional activities or behaviors that may lead to circadian disruption, such as night-shift work and atypical and inconsistent sleep-wake patterns that can lead to social jet lag. Future studies should more comprehensively characterize and measure the relevant light-related exposures and link these exposures to both time-independent biomarkers of circadian disruption and biomarkers of adverse health outcomes. This information should lead to improvements in human epidemiological and animal or in vitro models, more rigorous health hazard assessments, and intervention strategies to minimize the occurrence of adverse health outcomes due to these exposures.

The invention of electric light has facilitated a society in which people work, sleep, eat, and play at all hours of the 24-hour day. Although electric light clearly has benefited humankind, exposures to electric light, especially light at night (LAN), may disrupt sleep and biological processes controlled by endogenous circadian clocks, potentially resulting in adverse health outcomes. Many of the studies evaluating adverse health effects have been conducted among night- and rotating-shift workers, because this scenario gives rise to significant exposure to LAN. Because of the complexity of this topic, the National Toxicology Program convened an expert panel at a public workshop entitled “Shift Work at Night, Artificial Light at Night, and Circadian Disruption” to obtain input on conducting literature-based health hazard assessments and to identify data gaps and research needs. The Panel suggested describing light both as a direct effector of endogenous circadian clocks and rhythms and as an enabler of additional activities or behaviors that may lead to circadian disruption, such as night-shift work and atypical and inconsistent sleep-wake patterns that can lead to social jet lag. Future studies should more comprehensively characterize and measure the relevant light-related exposures and link these exposures to both time-independent biomarkers of circadian disruption and biomarkers of adverse health outcomes. This information should lead to improvements in human epidemiological and animal or in vitro models, more rigorous health hazard assessments, and intervention strategies to minimize the occurrence of adverse health outcomes due to these exposures.

Our overall goal is to use the mouse to identify genetic elements controlling sleep. We will use the Clock mutant mouse because of finding that Clock mutants, in addition to their circadian abnormalities, sleep less than wild-type mice. Over the past year, we have examined how the Clock mutation alters sleep and body temperature rhythms under stressful conditions. Correspondingly, body temperature decreased during the recovery dark period in wild-types but did not change in Clock/Clock mica. Finally, a negative rebound in delta power was observed in wild-type mica, but not in Clock/Clock mice. These results indicate that the Clock gene disrupts the pattern and amount of sleep, as well as the amplitude of the body temperature rhythm under baseline and stressful conditions. We have also examined sleep in neonatal pups to determine if pups could be used in mutagenesis screening. Our findings in mica, and in other studies in rats, that a simple behavior in the neonate can be used to detect genetic differences observed in adult sleep represent a 'proof of principle' that it will be possible to use behavioral states in the neonate to uncover unknown genes involved in the regulation of the sleep-wake cycle of mammals. Other studies carried out under this proposal are described.

From May 6-10, 1992, the Society for Research on Biological Rhythms held its third meeting at Amelia Island Plantation, Florida. The Society was formed in 1987 to promote the advancement of basic and applied research in all aspects of biological rhythms, to disseminate important research results concerning biological rhythms to the general public, to develop and enhance the eduction and training of students and researchers in the field and to foster interdisciplinary communication. This third meeting was successful in meeting the goals of the Society, particularly in the area of interdisciplinary communication. Researchers in the field of Biological Rhythms tend to be fragmented into many disciplines and are often divided along many different lines. One way of dividing the field is along frequency lines; while some workers study biological rhythms with a period of msec, others are interested in rhythms with periods in the range of minutes, hours (i.e. ultradian or pulsatile), a day (i.e. circadian) or a year (i.e. seasonal or circannual). The field is also divided along the lines of the major disciplines within biology since rhythms biologists can be either biochemists, molecular/cellular biologists, system physiologists, behaviorists and/or ecologists. In addition, while many workers study the basic biological mechanisms involved in generating rhythmicity, others are interested in the clinical applications of a better understanding of biological rhythmicity. Even within the clinical field, researchers fall into many traditional categories including psychiatry, endocrinology, neurology, oncology, cardiology and reproduction.

From May 9-13, 1990 the Society for Research on Biological Rhythms held its second meeting at Amelia Island Plantation, Florida. The Society was formed to promote the advancement of basic and applied research in all aspects of biological rhythms, to disseminate important research results concerning biological rhythms to the general public, to develop and enhance the education and training of students and researchers in the field and to foster interdisciplinary communication. This second meeting was successful in meeting the goals of the Society, particularly in the area of interdisciplinary communication. This second meeting promoted the interaction of workers in the various areas in a variety of different ways. First, there was a mixture of Symposia as well as slide and poster sessions on clinical and basic research topics. The Symposia were organized to insure that the entire frequency range of biological rhythms would be presented.

Partial contents: Organization of Animal Circadian Systems; Pulsatile Rhythms of Neuroendocrine Function; Neural Transplants and Restoration of Circadian Function; Stabilization of Periodic Processes Through Coupling of Oscillators; Photic Effects on Pacemakers; Pineal and Retinal Oscillators In Vitro; Computerized Data Acquisition; Involvement of Protein Synthesis in Circadian Rhythm Generation; Mechanisms of Vertebrate Pacemakers; Photoperiodism and Seasonal Rhythms; Human Rhythms and Sleep. Pharmacological Manipulation of Rhythms; Cellular, Molecular and Genetic Dissection of Clocks; Interaction Between Sleep and the Circadian System; Entraining Effects of Melatonin; Use of Periodogram Analysis and Related Procedures in Biological Rhythms Studies; Use of In Vitro Brain Slices in Studies of Circadian Function; Modulation and Control of Neural Oscillators; Chronobiology of Depression; Cellular and Molecular Basis of Rhythmicity; and Comparative Analysis of Rhythms. Keywords: Symposia.