Clocks & Sleep, Volume 5, Issue 3 (September 2023) – 12 articles

Increasing evidence suggests a correlation between changes in the composition of gut microbiota and sleep-related phenotypes. However, it remains uncertain whether these associations indicate a causal relationship. The genome-wide association study summary statistics data of gut microbiota (n = 18,340) was downloaded from the MiBioGen consortium and the data of sleep-related phenotypes were derived from the UK Biobank, the Medical Research Council-Integrative Epidemiology Unit, Jones SE, the FinnGen consortium. To test and estimate the causal effect of gut microbiota on sleep traits, a two-sample Mendelian randomization (MR) approach using multiple methods was conducted. A series of sensitive analyses, such as horizontal pleiotropy analysis, heterogeneity test, MR Steiger directionality test and “leave-one-out” analysis as well as reverse MR analysis, were conducted to assess the robustness of MR results. The genus Anaerofilum has a negative causal effect on getting up in the morning (odd ratio = 0.977, 95% confidence interval: 0.965–0.988, p = 7.28 × 10⁻⁵). A higher abundance of order Enterobacteriales and family Enterobacteriaceae contributed to becoming an “evening person”. Six and two taxa were causally associated with longer and shorter sleep duration, respectively. Specifically, two SCFA-produced genera including Lachnospiraceae UCG004 (odd ratio = 1.029, 95% confidence interval = 1.012–1.046, p = 6.11 × 10⁻⁴) and Odoribacter contribute to extending sleep duration. Two obesity-related genera such as Ruminococcus torques (odd ratio = 1.024, 95% confidence interval: 1.011–1.036, p = 1.74 × 10⁻⁴) and Senegalimassilia were found to be increased and decreased risk of snoring, respectively. In addition, we found two risk taxa of insomnia such as the order Selenomonadales and one of its classes called Negativicutes. All of the sensitive analysis and reverse MR analysis results indicated that our MR results were robust. Our study revealed the causal effect of gut microbiota on sleep and identified causal risk and protective taxa for chronotype, sleep duration, snoring and insomnia, which has the potential to provide new perspectives for future mechanistic and clinical investigations of microbiota-mediated sleep abnormal patterns and provide clues for developing potential microbiota-based intervention strategies for sleep-related conditions. Full article

Poor sleep is a major public health problem with implications for a wide range of critical health outcomes. Insomnia and sleep apnoea are the two most common causes of poor sleep, and recent studies have shown that these disorders frequently co-occur. Comorbid insomnia and sleep apnoea can substantially impair quality of life and increase the overall risk of mortality. However, the causal and physiological links between sleep apnoea and insomnia are unclear. It is also unknown whether having a higher risk for one condition can increase the risk of developing the other. Here, we investigated links between sleep apnoea and insomnia in a British population using a combination of self-reported questionnaires and causal inference. We found that 54.3% of the cohort had moderate insomnia, 9.4% had moderate sleep apnoea, and that 6.2% scored high for both conditions. Importantly, having a higher risk of sleep apnoea was associated with a higher risk of insomnia and vice versa. To determine the causal directionality between sleep apnoea and insomnia, we used Mendelian randomisation and found evidence that sleep apnoea could cause insomnia, but not the reverse. To elucidate how both sleep apnoea and insomnia were linked to each other, we looked at the behavioural markers of poor sleep. We found that feeling fatigued after sleeping and having noticeable sleep problems were linked to a higher burden of both sleep apnoea and insomnia. In conclusion, our results show that sleep apnoea increases the risk of developing insomnia, and both conditions can result in fatigue. We highlight the importance of considering and treating the symptoms of both conditions. Full article

A negative attitude toward sleep has greatly affected sleep habits. In addition to contributing to physical and metabolic disorders, poor sleep quality may cause emotional disturbances. This study aimed to measure sleep behavior and factors contributing to poor sleep quality in the Madinah region, Saudi Arabia. We also assessed whether the use of sleeping aids improved peoples sleep. Three hundred and ninety-nine adults in the Madinah region of Saudi Arabia participated in this cross-sectional study. Three data domains were collected using an online questionnaire between 30 January and 26 April 2022. In the first domain, the characteristics of participants were discussed. In the second domain, questions about sleep behavior were asked. In the third domain, we examined the types, frequency, and impact of sleep aid use. Out of the 399 participants, 154 (38.59%) reported sleep problems. A total of 64.94% of the 154 participants blamed stress as the leading cause of their sleep disorders, and 74.68% of those with sleep problems reported reduced productivity. Among those who reported having sleep problems, 46.10% used sleep aids, with Panadol night (antihistamine) being the most used, 49.30%, followed by Melatonin at 39.44%. Sleep quality improved by 67.6% among those who used sleep aids. A total of 71.8% of the participants think it is not safe to use sleep aids in the long term. Our findings suggest that sleep problems are a prevalent concern in Madinah, Saudi Arabia, and even though the use of sleep aids improved sleep quality, it should be considered an emerging and important public health objective in Saudi Arabia. Further studies are needed to evaluate sleep quality and the level of sleep aid usage among other Saudi Arabian regions. Full article

Achieving synchronization between the central and peripheral body clocks is essential for ensuring optimal metabolic function. Meal timing is an emerging field of research that investigates the influence of eating patterns on our circadian rhythm, metabolism, and overall health. This narrative review examines the relationship between meal timing, circadian rhythm, clock genes, circadian hormones, and metabolic function. It analyzes the existing literature and experimental data to explore the connection between mealtime, circadian rhythms, and metabolic processes. The available evidence highlights the importance of aligning mealtime with the body’s natural rhythms to promote metabolic health and prevent metabolic disorders. Specifically, studies show that consuming meals later in the day is associated with an elevated prevalence of metabolic disorders, while early time-restricted eating, such as having an early breakfast and an earlier dinner, improves levels of glucose in the blood and substrate oxidation. Circadian hormones, including cortisol and melatonin, interact with mealtimes and play vital roles in regulating metabolic processes. Cortisol, aligned with dawn in diurnal mammals, activates energy reserves, stimulates appetite, influences clock gene expression, and synchronizes peripheral clocks. Consuming meals during periods of elevated melatonin levels, specifically during the circadian night, has been correlated with potential implications for glucose tolerance. Understanding the mechanisms of central and peripheral clock synchronization, including genetics, interactions with chronotype, sleep duration, and hormonal changes, provides valuable insights for optimizing dietary strategies and timing. This knowledge contributes to improved overall health and well-being by aligning mealtime with the body’s natural circadian rhythm. Full article

Standardization plays a crucial role in ensuring the reliability, reproducibility, and interoperability of research data in the biomedical sciences. Metadata standards are one foundation for the FAIR (Findable, Accessible, Interoperable, and Reusable) principles of data management. They facilitate data discovery, understanding, and reuse. However, the adoption of metadata standards in biological research lags in practice. Barriers such as complexity, lack of incentives, technical challenges, resource constraints, and resistance to change hinder widespread adoption. In the field of chronobiology, standardization is essential but faces particular challenges due to the longitudinal nature of experimental data, diverse model organisms, and varied measurement techniques. To address these challenges, we propose an approach that emphasizes simplicity and practicality: the development of README templates tailored for particular data types and species. Through this opinion article, our intention is to initiate a dialogue and commence a community-driven standardization process by engaging potential contributors and collaborators. Full article

The visual and non-visual effectiveness of light is often determined by measuring the spectrally weighed irradiance on the corneal plane. This is typically achieved using spectral irradiance or illuminance measurements, captured in a hemispheric (2π) geometry with a diffuser. However, the human binocular field of view (FOV) is not a perfect hemisphere, as it is occluded both upward and downward. Previous research on FOV-restricted measurements is limited, leaving the error from using hemispheric measurements for non-visual quantities undefined. In our study, we tackled this issue by designing and 3D printing FOV occlusions as attachments to spectral measurement devices. We took measurements with and without the occlusion in various laboratory (light from different directions) and real-world lighting situations (light typically from above). Our findings reveal a reduction of visual and melanopic values due to the FOV occlusion. These ranged from negligible to more than 60% in realistic scenarios. Interestingly, the reduction was consistent for both visual and melanopic parameters, as the distribution of light in the FOV was generally spectrally homogeneous. An exception occurred in a specific artificial laboratory situation, where the melanopic daylight (D65) efficacy ratio changed by more than a factor of 2 solely because of the FOV occlusion. Additionally, we observed that head orientation had a marked effect on all quantities measured. In conclusion, our results highlight the potential for substantial errors when solely relying on vertical, hemispheric measurements in experiments and non-visual lighting design projects. We encourage the (additional) use of FOV occlusion in eye-level measurements for typical viewing directions, and we are providing open-source 3D-print files to facilitate this practice. Full article

Objectives: We test the hypothesis that the incidence of sleep problems is influenced by socio-demographic variables, particularly social deprivation and ethnicity. Methods: Self-reports of sleep duration and sleep difficulties (waking in the night, sleeping in the day, difficulty waking and snoring), personal wealth (household income, property-owning, etc.), ethnic group, employment, education, as well as post-code-based Townsend Social Deprivation, were extracted from UK Biobank’s cohort of c500,000 British-domiciled adults (40–70 years). Analyses contrasted the incidence of different sleep problems and a composite measure of these (the Problematic Sleep Index) across groups. Results: Almost one-third of participants reported sleeping shorter (24.7%), or longer (7.7%) than age-corrected recommended sleep durations. The incidence of shorter or longer sleep increased with social deprivation and varied with ethnicity. Snoring, waking during the night, finding it difficult to get up in the morning and sleeping in the daytime were subject to similar effects. The Problematic Sleep Index showed being younger, male, employed, home-owning, having a higher household income, having a higher level of educational achievement, and time in education were all associated with better sleep, as was living in a more affluent area and being White. Conclusions: Sleep problems in Britain show a social gradient, independently of a range of other demographic and social influences, suggesting that sleep quality differs with and between ethnic groups. These sleep inequalities suggest that the protective and recuperative effects of sleep are disproportionately distributed across society and should encourage us to consider the potential benefits of community-specific sleep interventions. Full article

(1) Background: In 2013, the results of a pioneer study on abnormalities in the levels and circadian rhythmicity of expression of circadian clock genes in cancerous thyroid nodules was published. In the following years, new findings suggesting the involvement of circadian clockwork dysfunction into malignant transformation of thyroid tissue were gradually accumulating. This systematic review provides an update on existing evidence regarding the association of these genes with thyroid tumorigenesis. (2) Methods: Two bibliographic databases (Scopus and PubMed) were searched for articles from inception to 20 March 2023. The reference lists of previously published (nonsystematic) reviews were also hand-searched for additional relevant studies. (3) Results: Nine studies published between 2013 and 2022 were selected. In total, 9 of 12 tested genes were found to be either up- or downregulated. The list of such genes includes all families of core circadian clock genes that are the key components of three transcriptional–translational feedback loops of the circadian clock mechanism (BMAL1, CLOCK, NPAS2, RORα, REV-ERBα, PERs, CRYs, and DECs). (4) Conclusions: Examination of abnormalities in the levels and circadian rhythmicity of expression of circadian clock genes in thyroid tissue can help to reduce the rate of inadequate differential preoperative diagnosis for thyroid carcinoma. Full article

Coronavirus disease (COVID-19) is a global pandemic, which is not only a severe public health issue but also significantly impacts the physical activity, sleep habits, and mental health of university students. Thus, we examined the association between behavioral restrictions due to COVID-19 and sleep patterns and mental health in first-year Japanese university students. Four hundred and twenty-two students (253 males and 169 females; age, 18.7 ± 1.0 years) participated in our questionnaire study. Under the behavioral restrictions due to COVID-19, 193 students (127 males and 66 females) responded to the questionnaire online from home. The participants did not visit the university during the survey period. The data acquired the year before the COVID-19 pandemic (2018 and 2019) were used as control data (126 males and 103 females). The questionnaire consisted of four sections: (1) demographic and lifestyle variables, (2) the Pittsburgh Sleep Quality Index, (3) the Japanese version of the Epworth Sleepiness Scale, and (4) the Patient Health Questionnaire-9. Our data revealed that self-restraint due to COVID-19 was associated with better sleep and mental health. In addition, mental health was independent of sleep, while sleep was related to mental health. These differences were more pronounced in male than in female students. This finding could be due to physical activity at night, part-time work, and long commuting times during the pre-pandemic period. Full article

Social restriction measures (SRM) implemented during the COVID-19 pandemic led to a reduction in time spent outdoors (TSO). The aim of this study was to describe TSO and evaluate its association with sleep outcomes, optimism, happiness and health-status before and during SRM. Two online surveys were conducted in 2017 (N = 1004) and 2020, during SRM (N = 1010), in samples representative of the age, sex and region of the Austrian population. Information on the duration of TSO, sleep, optimism, happiness and health-status was collected. Multivariable-adjusted logistic regression models were used to study the association of TSO with chronic insomnia, short sleep, late chronotype, optimism, happiness and self-rated health-status. The mean TSO was 3.6 h (SD: 2.18) in 2017 and 2.6 h (SD: 1.87) during times of SRM. Men and participants who were older, married or in a partnership and lived in a rural area reported longer TSO. Participants who spent less time outdoors were more likely to report short sleep or a late chronotype in both surveys and, in 2020, also chronic insomnia. Less TSO was associated with lower happiness and optimism levels and poor health-status. Our findings suggest that TSO may be a protective factor for sleep, mood and health, particularly during stressful and uncertain times. Full article

The main aim of this study was to explore how melatonin onset timing and phase angle to bedtime in healthy older adults are impacted by prior light exposure. A total of 13 healthy older (ages 56–74) individuals were studied on two successive evenings. Prior to the first evening, the participants were in self-selected lighting conditions for the first 4–6 h of the day and then were in dim light (3 lux) until their scheduled bedtime. On the second day, individuals from Project A remained in the dim lighting conditions throughout the entire day but those in Project B were in more typical indoor lighting (~90 lux) throughout the day. On both evenings, hourly blood samples were collected and assayed for melatonin, and melatonin onset timing and phase angle to sleep onset was determined. Overall, melatonin onset was earlier and the phase angle was larger on Night 1 than on Night 2. In Project A there was no significant difference between melatonin onset on night 1 vs. night 2. However, in Project B melatonin onset was significantly later on Night 2 (in typical indoor lighting) than on Night 1 (in dim lighting). Our results suggest that in older people, uncontrolled bright light early in the day did not impact the timing of dim light melatonin onset (DLMO) when assessed later that same evening. However, in older adults, exposure to ordinary room light during melatonin phase assessment appeared to suppress melatonin, leading to a later observed time of melatonin onset, as has been reported previously for young adults. Full article