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

Hannah E Laue; Margaret R Karagas; Modupe O Coker; David C Bellinger; Emily R Baker; Susan A Korrick; Juliette C Madan

doi:10.1038/s41390-021-01785-z

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

Pediatr Res. 2022 Aug;92(2):580-591. doi: 10.1038/s41390-021-01785-z. Epub 2021 Nov 4.

Authors

Hannah E Laue¹, Margaret R Karagas², Modupe O Coker^{2

3}, David C Bellinger⁴, Emily R Baker⁵, Susan A Korrick^#^{6

7}, Juliette C Madan^#^{2

8}

Affiliations

¹ Department of Epidemiology, Geisel School of Medicine at Dartmouth College, Hanover, NH, USA. Hannah.E.Laue@Dartmouth.edu.
² Department of Epidemiology, Geisel School of Medicine at Dartmouth College, Hanover, NH, USA.
³ School of Dental Medicine, Rutgers, The State University of New Jersey, Newark, NJ, USA.
⁴ Department of Neurology, Harvard Medical School and Boston Children's Hospital, Boston, MA, USA.
⁵ Department of Obstetrics and Gynecology, Dartmouth Hitchcock Medical Center, Lebanon, NH, USA.
⁶ Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
⁷ Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
⁸ Departments of Pediatrics and Psychiatry, Children's Hospital at Dartmouth, Lebanon, NH, USA.

^# Contributed equally.

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.

Publication types

Research Support, U.S. Gov't, Non-P.H.S.
Research Support, N.I.H., Extramural

MeSH terms

Animals
Child
Child, Preschool
Cross-Sectional Studies
Female
Gastrointestinal Microbiome* / genetics
Humans
Male
Microbiota*
RNA, Ribosomal, 16S / genetics
Vitamin B 6

Substances

RNA, Ribosomal, 16S
Vitamin B 6

Abstract

Publication types

MeSH terms

Substances

Grants and funding