Sleep Duration and the Gut Microbiota in Infancy: an exploration of the determinants of sleep and the association between sleep and the gut microbiota at 3 months of age in a Canadian birth cohort

• Author / Creator

  Matenchuk, Brittany A.

• RATIONALESleep duration is critical to growth, cognitive development, and overall health status in infancy. Strategies to ensure that national recommendations for sleep duration in infants are met require knowledge of perinatal factors that affect infant sleep. Parental socioeconomic status (income, education, and occupation) has been linked to shorter infant sleep duration. Study I attempts to explain which factors mediate this relationship. Recent research has shown that sleep and the gut microbiome are intimately linked – as little as a few days of sleep deprivation leads to overgrowth of the intestinal microbiome. The influence of short sleep on the gut microbiota in infancy may be exceedingly important, as the composition of the infant gut microbiota plays a significant role in the development of the immune system. OBJECTIVESStudy I - To investigate the mechanistic pathways linking maternal education and infant sleep. Study II – To investigate the relationship between sleep duration and gut microbiota composition at 3 months of age after adjustment for significant covariates.METHODSStudy I - An observational study was conducted on 619 infants whose mothers were enrolled at the Edmonton site of the CHILD birth cohort. Infant sleep duration at 3 months was assessed using the Brief Infant Sleep Questionnaire (BISQ). Maternal education was collected via maternal report. Prenatal and postnatal depression scores were obtained from the 20-item Center for Epidemiologic Studies Depression Scale (CES-D). Birth records and maternal report were the source of covariate measures. Mediation analysis (PROCESS v3.0) was used to examine the indirect effects of maternal education on infant sleep duration mediated through prenatal depression and birth mode.Study II - A sub-study was conducted on 437 infants for whom microbiome data was available whose mothers were enrolled at the Edmonton site of the CHILD birth cohort. Infant gut microbiota were profiled using 16S rRNA sequencing from faecal samples collected at 3 months of age. Nonparametric statistical testing and logarithmic regression modelling was used to examine the relationship between sleep and abundance of gut microbial taxa. MaAsLin was utilized to determine which microbial taxa were associated with shorter infant sleep while adjusting for covariates. Linear regression was conducted on arcsine square root transformed gut bacterial relative abundance.RESULTSStudy I - At 3 months of age, infants sleep on average 14.1 hours. Sixty-one percent of infants met the National Sleep Foundation recommendation of ≥14 hours. Lower maternal education and prenatal depression were associated with significantly shorter infant sleep duration. Emergency cesarean section birth was associated with 1-hour shorter sleep duration at 3 months compared to vaginal birth without intrapartum antibiotic prophylaxis. Thirty percent of the effect of lower maternal education on infant total sleep duration was mediated sequentially through prenatal depression and birth mode (Total Indirect Effects: -0.12, 95%CI: -0.22, -0.03, p<0.05).Study II - Sleep duration (as a continuous measure) was negatively associated with the relative abundance of Clostridium (Spearman Rho: -0.10, p=0.03). Short sleepers (<14 hours per 24-hour period) were more likely to be colonized with Enterococcus (76.5% vs 65.2%, p=0.01; Exact) and Clostridium (80.6% vs 67.4%, p<0.01) and less likely to be colonized with Erwinia ( 5.9% vs 12.7%, p=0.02) than infants obtaining ≥14 hours of sleep. Additionally, arcsine square root transformed Lachnospiraceae was positively associated with continuous sleep duration in exclusively breastfed (β:-0.07, 95% CI: -0.12; -0.02;p=0.01) and in infants born vaginally without exposure to maternal antibiotics (β:-0.07, 95% Confidence Interval [CI]: -0.13; -0.01;p=0.02) following adjustment. Erwinia was the only bacterial taxa identified by MaAsLin to be associated with short sleep following adjustment for metadata (beta-coefficient: -0.00065, p=0.016). CONCLUSIONSPrenatal depression and birth mode sequentially mediate the effect of maternal education on infant sleep duration. Furthermore, the relative abundances and colonization frequency of biologically important gut bacteria for infant growth are significantly associated with infant sleep duration at three months of age. Additional counselling on infant sleep for mothers who experience prenatal depression, or an emergency caesarean section birth, may help to decrease the sleep duration gap between infants of mothers with and without postsecondary education. ACKNOWLEDGEMENTSThe author would like to acknowledge the CHILD study participants and Investigators, without whom this research would not be possible.

• Subjects / Keywords

  • socioeconomic status
  • microbiota
  • pediatric
  • infant sleep
  • birth mode
  • sleep

• Graduation date

  Spring 2019

• Type of Item

  Thesis

• Degree

  Master of Science

• DOI

  https://doi.org/10.7939/r3-1nmx-tv30

• License

  Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.