Variation in Infant Feeding and Sleep-Wake Patterns are Associated with Differences in the Gut Microbiome in Toddlerhood

• In Event: Infant sleep and the development of obesity: Direct and indirect associations in four longitudinal cohorts

Abstract

Sleep-wake rhythm misalignment in animal models negatively influences the gut microbiome (GM) and increases obesity risk; however, there are limited human studies exploring this relationship, and few studies characterizing infants and toddlers. Early and rapid weight gain, formula feeding, and early introduction to solid foods during infancy have been identified as strong determinants of early life and persistent obesity. The aim of this study was to examine differences in the GM composition in toddlerhood by feeding practices, sleep-wake patterns, and rapid weight gain that occurred in infancy.

Pregnant, Latina women with obesity recruited from the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) program participated in a randomized controlled trial testing an educational intervention targeting infant development to prevent the incidence of infant overweight. The intervention was delivered across infancy until 12 months and participants were followed until 36 months. At one, six, and 12 months, mothers completed feeding surveys and the Brief Infant Sleep Questionnaire. Rapid weight gain was defined as a > 0.67 positive change in weight-for-age Z-score from birth to six months. Among a subset of children (n=35), feces were collected at 36 months. Microbial DNA was extracted and sequenced based on the V4 region of the 16S rRNA gene which is common across all bacteria. Feeding information (milk type and age at solid foods introduction), rapid weight gain, sleep duration, timing, and diurnal/nocturnal patterning were examined in relation to GM diversity metrics using Kruskal-Wallis and PERMANOVA comparisons.

GM diversity at 36 months of age differed by rapid weight gain status during infancy with lower microbial richness in those who experienced rapid weight gain (p=0.02). GM diversity in toddlerhood varied by aspects of infant sleep and feeding during the first 12 months of life with six months emerging as an important time point. At six months, babies with bedtimes earlier than 9:00 pm had a richer (p=0.03) and more even (p=0.03) microbiome composition in toddlerhood than babies with later bedtimes. Infants at six months of age with a greater proportion of nocturnal sleep per their total 24h sleep had lower microbial richness (p=0.02) and phylogenetic diversity (p=0.001) in toddlerhood. Further, at six months, napping more than five hours during the day was associated with greater phylogenetic richness than napping ≤
five hours (p<0.005). Overall community structure of the GM differed between children who were introduced to solid foods before six months and  six months which was driven by taxa abundance. GM diversity did not differ by breastmilk vs. formula feeding but persistence of exclusive breastmilk vs. formula feeding through 12 months resulted in differences in the overall GM community structure (driven by presence/absence and phylogeny; p<0.05) at 36 months of age.

Together, these data suggest that feeding and sleep practices in infancy may influence the GM in ways that persist into toddlerhood. Understanding how early life sleep and feeding practices influence the GM is important for elucidating the developmental origins of obesity. Further work is needed using temporal repeated measures in this understudied population.

Authors

• Magdalena Olson, Arizona State University
  Presenting Author

• Fang Zhou, Arizona State University

• Kiley Vander Wyst, Arizona State University

• Samantha Toffoli, Arizona State University

• Elizabeth Reifsnider, Arizona State University

• David P. McCormick, University of Texas Medical Branch at Galveston

• Megan E. Petrov, Arizona State University

• Corrie M. Whisner, Arizona State University