Association of the Infant Gut Microbiome With Early Childhood Neurodevelopmental Outcomes An Ancillary Study to the VDAART Randomized Clinical Trial

IMPORTANCE In animal models, the early life gut microbiome influences later neurodevelopment. Corresponding data in human populations are lacking. OBJECTIVE To study associations between the gut microbiome in infants and development at preschool age measured by the Ages and Stages Questionnaire, third edition (ASQ-3). DESIGN, SETTING, AND PARTICIPANTS This ancillary cohort study of the Vitamin D Antenatal Asthma Reduction Trial (VDAART) used data from 715 participants who had development assessed at 3 years of age by the ASQ-3, which included scores in 5 domains (gross motor skills, fine motor skills, problem solving, communication, and personal and social skills). A total of 309 stool samples were collected from infants aged 3 to 6 months for microbiome analysis using 16S rRNA gene sequencing. EXPOSURES Infant gut microbiome. MAIN OUTCOMES AND MEASURES Continuous ASQ-3 scores and typical vs potential delay in the 5 developmental domains. Factor scores for bacterial coabundance groups were used as predictors in regression models of continuous ASQ-3 scores. Logistic regression was used to examine bacterial coabundance scores and odds of scoring below the threshold for typical development. Multivariate analysis examined the abundance of individual taxa and ASQ-3 scores. RESULTS The 309 participants (170 [55.0%] male) with ASQ-3 scores and stool samples were ethnically diverse (136 [44.0%] black, 41 [13.3%] Hispanic, 86 [27.8%] white, and 46 [14.9%] other race/ethnicity); the mean (SD) age at ASQ-3 assessment was 3.0 (0.07) years. Coabundance scores dominated by Clostridiales (Lachnospiraceae genera and other, unclassified Clostridiales taxa) were associated with poorer ASQ-3 communication (beta, -1.12; 95% CI, -2.23 to -0.01; P=.05) and personal and social (beta, -1.44; 95% CI, -2.47 to -0.40; P=.01) scores and with increased odds of potential delay for communication (odds ratio [OR], 1.69; 95% CI, 1.06 to 2.68) and personal and social skills (OR, 1.96; 95% CI, 1.22 to 3.15) per unit increase in coabundance score. The Bacteroides-dominated coabundance grouping was associated with poorer fine motor scores (beta, -2.42; 95% CI, -4.29 to -0.55; P=.01) and with increased odds of potential delay for fine motor skills (OR, 1.52; 95% CI, 1.07 to 2.16) per unit increase in coabundance score. Multivariate analysis detected similar family-level and order-level associations. CONCLUSIONS AND RELEVANCE These findings suggest an association between infant gut microbiome composition and communication, personal and social, and fine motor skills at age 3 years. The majority of associations were driven by taxa within the order Clostridiales.