Children who go to bed early have a richer gut microbiome and better sleep efficiency, paving the way for potential interventions that leverage the gut-brain connection to improve sleep quality and overall health.
Study: Characteristics of gut flora in children who go to bed early versus late. Image Credit: Africa Studio / Shutterstock
In a recent study published in the journal Scientific Reports, researchers investigated the gut microbial composition and metabolite expression of 88 healthy children to evaluate the role of sleep timings and routines on gut health and associated outcomes.
Multi-omics sequencing of participants’ fecal samples revealed that the gut microbial composition (beta diversity; P = 0.045) varied significantly between early (before 9:30 pm) and late sleepers. Specific species such as Akkermansia muciniphila (P = 0.00024), Alistipes finegoldii (P = 0.028), and Holdemania filiformis (P = 0.0077) were notably more abundant in early sleepers. Alpha diversity indices (Simpson’s index, P = 0.0011; Shannon’s index, P = 0.0013) validated these findings and demonstrated a significantly higher diversity and abundance of beneficial gut microbiota in early sleepers compared to their late-sleeping counterparts.
Together, these findings support and highlight the importance of the ‘early to bed…’ refrain in children (and potentially adolescents), emphasizing the beneficial impacts of good and regular sleep habits. It may further form the basis for future pharmacological interventions against sleep disorders by leveraging the hitherto untapped gut-brain axis.
Background
Sleep, the state of altered consciousness, and reduced activity (physical and mental) are essential for both recovery and normal growth and development. Recent studies suggest that sleep plays a vital role in housekeeping, allowing for the removal of toxic metabolites from the brain, anabolism in muscles, and enhanced generalized recovery.
In today’s world of rapidly rising chronic disease incidence, sleep (alongside other good health behaviors such as diet and physical activity) is increasingly being investigated for its associations with human health and wellbeing. A growing body of evidence suggests that adequate sleep duration and regular sleep routines can significantly attenuate the risk of cardiovascular diseases, neurological distress, obesity, and diabetes. These findings are especially relevant for children and adolescents, wherein sleep has been shown to extensively modulate average growth and development.
Despite substantial research on the impacts of sleep (particularly ‘sleep duration’) on children’s health, the potential implications of sleep on gut microflora remain unknown. While most school-age children are known to maintain regular routines on school days, a portion of them are expected to alter these routines significantly (especially sleep timings) on weekends and holidays, potentially increasing the risk of adverse health outcomes.
“Research has demonstrated that establishing early bedtimes and mornings can bring numerous advantages for children. These advantages encompass ensuring sufficient sleep and establishing regular patterns, which are crucial for children’s well-being and educational achievements. While prior investigations have primarily concentrated on observing children’s sleep patterns and implementing interventions to enhance these patterns, there exists a substantial research gap in examining children’s sleep from a physiological and metabolic viewpoint.”
About the study
The present study aims to address existing knowledge gaps by using next-generation multi-omics sequencing to unravel the metabolic mechanisms (gut microbial composition and metabolic pathways) associated with a spectrum of sleep durations and bed timings. Study data was obtained from 88 healthy children (ages 2-14) from Lanzhou City, Gansu province, Northwest China (female n = 44). Children were excluded from the study if: 1. Their parents had not successfully completed an author-administered course on sleep-dairy maintenance, 2. Had consumed antibiotics in the 30 days preceding study initiation, 3. Were currently suffering from an antibiotic infection.
Data collection included a pediatric assessment of participants’ birth weight, birth length, daily physical activity duration, bowel movement frequency, meal consumption frequency, and current height and weight. Additionally, psychological assessments of participants and their parents were conducted. Biological sample collection included blood and fecal samples for multiomics procedures.
“Sleep diary monitoring and recording includes: Time to sleep, Woke up a few times during sleep, How long did you sleep at night?, sleep efficiency(Total time sleeping/total time lying in bed), number of dreams, Sleep Quality Score (1 is poor, 5 is fair, 10 is excellent), Daytime nap time(min), How long did you sleep at night? Total time spent in bed at night, Daytime nap time. The analysis revealed that the early sleep group had a significantly lower ‘time to fall asleep’ (P = 1e-06), fewer ‘nighttime waking incidents’ (P = 0.015), and higher ‘sleep efficiency’ (P = 9.9e-06) compared to late sleepers.”
Metagenomics sequencing was carried out using the DNBSEQ Platform, following which the Metaphlan 3.0 software was used for participant-specific gut microbiome taxonomic profiling. Functional metabolic pathways profiling was achieved using the HUMAnN 3.0 database. Specific pathways such as the aerobic breakdown of toluene I (P = 0.025), the superpathway of threonine metabolism (P = 0.027), and the second pathway for L-lysine biosynthesis (P = 0.028) were found to be significantly upregulated in early sleepers, suggesting a distinct metabolic profile that might be linked to their improved gut health. Alpha and Beta diversity indices were computed in R software (v4.0.3; vegan and ape packages). Finally, the impacts of sleep on gut microbiome abundance profiles were estimated using Permutational Multivariate Analysis of Variance (PERMANOVA).
Study findings
The study design ensured that 88 participants were divided equally between early sleep (bedtime before 9:30 p.m.) and late sleep (bedtime after 9:30 p.m.) cohorts, each with equal male and female representation. Descriptive analysis of covariates (age, sex, daily behaviors, geographical distribution, physical activity) revealed no statistical baseline differences between early—and late-sleep cohorts.
Notably, early sleep participants significantly outperformed their late sleep counterparts across almost all measured sleep quality metrics (P-values ranging from 1e-06 to 0.015). In contrast, sleep duration, number of dreams, and nap duration were statistically indistinguishable between cohorts.
Substantial inter-cohort differences were noted in the microbiome species composition and relative abundance, with early sleepers demonstrating a significantly higher abundance of Bacteroidetes, Verrucomicrobia, and Firmicutes phyla (P = 0.045). Genus-level alpha and beta diversity were also substantially higher in early sleepers.
“During the analysis of metabolic pathways, it was observed that various metabolic routes experienced a significant increase. These pathways encompass the aerobic breakdown of toluene I through o-cresol (P = 0.025), the aerobic breakdown of toluene II through 4-methylcatechol (P = 0.025), the superpathway of threonine metabolism (P = 0.027), the second pathway for L-lysine biosynthesis (P = 0.028), the TCA cycle with incomplete reduction (P = 0.039), the second pathway for L-ornithine biosynthesis (P = 0.040), and the initial step in formaldehyde oxidation (P = 0.041).”
Conclusions
The present study provides the first evidence of a direct relationship between sleep and gut microflora, highlighting the importance of early and regular sleep in younger children (ages 2-14). Early sleepers showed higher abundances of beneficial species such as Akkermansia muciniphila and Alistipes finegoldii as well as increased activity in multiple metabolic pathways that support gut health. Study findings revealed that early sleepers harbor greater diversity and abundance of beneficial gut bacteria, directly impacting metabolic pathways and overall health for the better. Associations drawn between sleep patterns and metabolic pathways may further pave the way for future anti-sleep disorder pharmacological interventions.