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JAMA Netw Open. 2019 Mar 1;2(3):e190905. doi: 10.1001/jamanetworkopen.2019.0905.

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

Author information

1
Department of Population Medicine, Harvard Medical School, Harvard Pilgrim Health Care Institute, Boston, Massachusetts.
2
Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
3
Channing Division of Network Medicine, Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts.
4
The Jackson Laboratory for Genomic Medicine, Farmington, Connecticut.
5
Department of Medicine, Boston University School of Medicine, Boston, Massachusetts.
6
Division of Allergy, Immunology, and Pulmonary Medicine, Washington University School of Medicine in St Louis, St Louis, Missouri.
7
Department of Allergy and Research and Evaluation, Kaiser Permanente Southern California Region, San Diego and Pasadena.
8
Department of Pediatrics, University of Rochester, Rochester, New York.

Abstract

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 (β, -1.12; 95% CI, -2.23 to -0.01; P = .05) and personal and social (β, -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 (β, -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.

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