Abstract
Introduction: Healthy infant development is driven by the maturation of different physiological processes. Two crucial processes are the establishment of sleep rhythms and the growth of a complex holobiontic ecosystem with gut bacteria. Studies have shown a bi-directional link between sleep and gut bacteria in animal models and human adults. However, no study has investigated how these two processes are linked in the first year of life nor how they contribute to healthy behavioral development.
Materials and Methods: We quantified habitual sleep (actigraphy-derived sleep composites Sleep Day, Sleep Night, Sleep Timing, Sleep Variability, and Sleep Activity), gut bacteria markers (16S rRNA gene profiling for computing bacterial diversity, enterotype, and bacterial maturation index), and behavioral development (Ages and Stages Questionnaire) in 162 infants at 3, 6 and 12 months of age. With multilevel and regression models we analyzed links between habitual sleep and gut bacteria, with random intercept cross-lagged panel models we evaluated interactions with behavioral developmental outcomes. Furthermore, in a subset of 32 6-months-old infants, we collected high-density EEG data during the first 2-h of nighttime sleep to quantify slow-wave activity, theta power, and sigma power.
Results: We found evidence of a sleep-gut link: daytime sleep (Sleep Day) was negatively linked to gut bacteria diversity (p = 0.02), and nighttime sleep fragmentation (Sleep Activity) was positively linked to bacterial maturation index (p = 0.03) and enterotype (p = 0.048). Sleep Variability was linked to enterotype patterns (p = 0.02). We also found evidence of a sleep-brain-gut link: The two enterotypes differed in slow-wave activity (p = 0.02).
Lastly, we found associations between both gut bacteria and habitual sleep and behavioral development both at the same age and predictive for later ages. General patterns revealed that habitual sleep was associated more strongly with personal-social development, with daytime sleep showing most associations. Gut bacteria were associated mainly with gross motor development, with bacterial diversity showing most associations.
Conclusions: We find novel evidence for a sleep-brain-gut link in infants that is relevant for behavioral development. This research provides sleep and gut bacteria targets as fundamental anchors for non-invasive modification to promote healthy development. Considering that many adult diseases root in early childhood, early interventions can improve lifelong health.
Acknowledgements: This research was funded by the University of Zurich (Clinical Research Priority Program “Sleep and Health”, Forschungskredit FK-18-047, Faculty of Medicine), the Swiss National Science Foundation (PCEFP1-181279, P0ZHP1-178697), Foundation for Research in Science and the Humanities (STWF-17-008), and the Olga Mayenfisch Stiftung. We thank the parents and infants for participating in our study.
Schoch, S