Exploring a new developmental concept: the sleep-brain-gut axis in infants
1Department of Pulmonology, University Hospital Zurich, Zurich, CH; 2University of Zurich, Zurich, CH; 3Department of Food Science, University of Copenhagen, DK; 4Child Development Center, University Children's Hospital Zurich, Zurich, CH; 5Department of Child and Adolescent Psychiatry and Psychotherapy, Psychiatric Hospital, University of Zurich, CH; 6Department for Gastroenterology and Hepatology, University Hospital Zurich, Zurich, CH; 7Genetic Diversity Centre (GDC), Department of Environmental Systems Science, ETH Zurich, Zurich, CH; 8Department of Psychology, University of Fribourg, Fribourg, CH
Evidence from adults and animals reveals a relationship between sleep and gut bacteria. However, it is unclear when in life this relationship emerges. Neuronal networks, sleep regulation, and gut bacteria undergo significant development; we thus hypothesized their co-maturation and interaction across human infancy.
From 162 infants (3, 6, 12mo) we quantified habitual sleep (actigraphy), gut bacteria (16S-rRNA gene profiling), and behavioral development (Ages and Stages Questionnaire). For neuronal markers we measured high-density EEG during nighttime sleep (n= 32, 6mo). Following standard processing (bandpass 0.5–50 Hz, down-sampling to 128 Hz, sleep stage scoring, artifact rejection, FFT), we computed EEG power in the delta (1–4.5 Hz), theta (4.75–7.75 Hz) and sigma (10–16 Hz) frequencies. We analyzed sleep-brain-gut associations using multilevel and regression models.
Overall, we report a sleep-gut link: First, daytime sleep was linked to gut bacterial diversity (p=0.02), and nighttime sleep fragmentation was linked to gut bacteria maturity (p=0.03) and enterotype evolution (p=0.048). Second, a sleep-brain-gut axis was found: Enterotype at 6mo was associated with delta power (p=0.02). Theta power at 6mo predicted later bacterial diversity (p=0.04). Third, both gut bacteria and habitual sleep were linked with behavioral development, both concurrently and predictively in longitudinal associations, with the strongest associations at 3mo.
We find evidence for a sleep-brain-gut link in infants, with a sensitive period at 3mo. As both sleep and gut bacteria can be modified non-invasively, this new concept represents a promising health target.