Dataset Information

Sex-specific relationships of the infant microbiome and early-childhood behavioral outcomes.

ABSTRACT:

Background

A link between the gut microbiome and behavior is hypothesized, but most previous studies are cross-sectional or in animal models. The modifying role of host sex is poorly characterized. We aimed to identify sex-specific prospective associations between the early-life gut microbiome and preschool-age neurobehavior.

Methods

In a prospective cohort, gut microbiome diversity and taxa were estimated with 16S rRNA sequencing at 6 weeks, 1 year, and 2 years. Species and gene pathways were inferred from metagenomic sequencing at 6 weeks and 1 year. When subjects were 3 years old, parents completed the Behavioral Assessment System for Children, second edition (BASC-2). A total of 260 children contributed 523 16S rRNA and 234 metagenomics samples to analysis. Models adjusted for sociodemographic characteristics.

Results

Higher diversity at 6 weeks was associated with better internalizing problems among boys, but not girls [β_Boys = -1.86 points/SD Shannon diversity; 95% CI (-3.29, -0.42), p_Boys = 0.01, β_Girls = 0.22 (-1.43, 1.87), p_Girls = 0.8, p_interaction = 0.06]. Among other taxa-specific associations, Bifidobacterium at 6 weeks was associated with Adaptive Skills scores in a sex-specific manner. We observed relationships between functional features and BASC-2 scores, including vitamin B6 biosynthesis pathways and better Depression scores.

Conclusions

This study advances our understanding of microbe-host interactions with implications for childhood behavioral health.

Impact

This is one of the first studies to examine the early-life microbiome and neurobehavior, and the first to examine prospective sex-specific associations. Infant and early-childhood microbiomes relate to neurobehavior including anxiety, depression, hyperactivity, and social behaviors in a time- and sex-specific manner. Our findings suggest future studies should evaluate whether host sex impacts the relationship between the gut microbiome and behavioral health outcomes.

SUBMITTER: Laue HE

PROVIDER: S-EPMC9065210 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Publications

Sex-specific relationships of the infant microbiome and early-childhood behavioral outcomes.

Laue Hannah E HE Karagas Margaret R MR Coker Modupe O MO Bellinger David C DC Baker Emily R ER Korrick Susan A SA Madan Juliette C JC

Pediatric research 20211104 2

<h4>Background</h4>A link between the gut microbiome and behavior is hypothesized, but most previous studies are cross-sectional or in animal models. The modifying role of host sex is poorly characterized. We aimed to identify sex-specific prospective associations between the early-life gut microbiome and preschool-age neurobehavior.<h4>Methods</h4>In a prospective cohort, gut microbiome diversity and taxa were estimated with 16S rRNA sequencing at 6 weeks, 1 year, and 2 years. Species and gene ...[more]

PMID: 34732816

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Project description:IntroductionVery Low Birth Weight (VLBW) infants, born weighing less than 1,500 grams, are at risk for both gut dysbiosis and later neuropsychological developmental deficits. Behavioral effects, while related to neurodevelopment, are often more subtle and difficult to measure. The extent of later neurobehavioral consequences associated with such microbial dysbiosis has yet to be determined. We explored associations between the infants' gut microbiome and early childhood behavior at 4 years of age and identified the bacterial taxa through a multivariate analysis by linear models.MethodsParents completed the Child Behavior Checklist (CBCL) focused on different DSM diagnostic categories: affective, anxiety, pervasive developmental, attention deficit/hyperactivity, and oppositional defiant. All the CBCL scores were corrected for gender, delivery method, gestational age, infant birth weight, occurrence of sepsis, and days on antibiotics prior statistical analyses. Canonical correlation analysis (CCA) was performed to determine the relationship between early life gut microbiome and the adjusted CBCL scores. The association of bacterial Amplicon sequence Variants (ASVs) to the CBCL scores were tested with multivariate analysis by linear models (MaAsLin).ResultsNineteen children who were previously born with very low birth weight and studied while hospitalized in the Neonatal Intensive Care Unit (NICU) were included in this study. Statistically significant associations were observed between early life gut bacteria such as Veillonella dispar, Enterococcus, Escherichia coli, and Rumincococcus to later behavior at 4 years. No significant association could be observed with early-life gut microbiome alpha diversity and behavioral measures at 4 years.DiscussionThese preliminary observational data provide insight into the relationships between VLBW gut microbiome dysbiosis and childhood behavior. This study contributes to the literature on gut microbiome analysis by examining various behavioral domains using a standardized tool linked to the Diagnostic and Statistical Manual of Mental Disorders (DSM).

Project description:ImportanceIn animal models, the early life gut microbiome influences later neurodevelopment. Corresponding data in human populations are lacking.ObjectiveTo 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 participantsThis 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.ExposuresInfant gut microbiome.Main outcomes and measuresContinuous 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.ResultsThe 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 relevanceThese 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.

Project description:ObjectivesTo evaluate a preventative behavioral intervention for managing early childhood caries (ECC) in a cohort of high-risk children.MethodsThis pragmatic trial of the MySmileBuddy Program (MSB) evaluated preventive behavioral outcomes in a 1-y community health worker-delivered intervention to prevent ECC progression. Pre-/postintervention surveys assessed parent-reported child engagement in therapeutic toothbrushing (i.e., adult-assisted brushing with fluoridated toothpaste twice daily) and caries-related dietary behaviors and barriers. Generalized linear model with identity link for continuous variables and logit link for dichotomous outcomes evaluated pre-/postintervention comparisons and generalized estimating equations accounted for within-participant correlation (α = 0.05).ResultsAmong 1,130 children with postintervention data, the average age was 3.97 y, 99% were Medicaid insured, and 88% were Hispanic. Most parents (95%) were mothers/grandmothers, married or in a committed partnership (75%), unemployed (62%), and with modest education (80% high school degree or less). The odds of reported therapeutic brushing nearly doubled (n = 864; odds ratio [OR] = 1.79, 95% confidence interval [CI] = 1.46, 2.20, P < 0.001); day and night bottle/sippy cup frequencies dropped 0.29 units (n = 871; 95% CI = -0.37, -0.33, P < 0.001) and 0.22 units (n = 1,130; 95% CI = -0.30, -0.15, P < 0.001); nighttime breastfeeding reduced 0.15 units (n = 870; 95% CI = -0.21, -0.10, P < 0.001); sharing utensils reduced 0.30 units (n = 572; 95% CI = -0.39, -0.21, P < 0.001); not using sugary foods to calm child improved 0.37 units (n = 664; 95% CI = 0.31, 0.44, P < 0.001); odds of eating meals and snacks at a table increased (n = 572; OR = 1.57, 95% CI = 1.28, 1.93, P < 0.001; n = 572; OR = 1.80, 95% CI = 1.50, 2.15, P < 0.001) respectively; and reducing barriers to behaviors improved 0.38 units for toothbrushing (n = 666; 95% CI = 0.31, 0.44, P < 0.001) and 0.33 units for diet (n = 668; 95% CI = 0.29, 0.38, P < 0.001).ConclusionDespite limitations inherent to pragmatic trials, significant behavioral changes suggest that MSB yielded an important salutary impact. Forthcoming mediation analyses will explore causal pathways. Findings support integration of MSB's behavior change program in caries management initiatives.Knowledge transfer statementThe results of this study can be used by clinicians, public health leaders, and researchers to inform the development and implementation of community-based, preventative behaviorally focused early childhood caries prevention programs. Study findings may enhance the understanding of the impact of behavioral interventions that engage parents of young children and could lead to more effective prevention for populations at high-risk of caries.

Dataset Information

Sex-specific relationships of the infant microbiome and early-childhood behavioral outcomes.

Background

Methods

Results

Conclusions

Impact

Publications

Sex-specific relationships of the infant microbiome and early-childhood behavioral outcomes.

Similar Datasets

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