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Early-life gut microbiota and attention deficit hyperactivity disorder in preadolescents

Pediatric Research volume 93, pages 2051–2060 (2023)Cite this article

Abstract

Background

Gut microbiota maturation coincides with nervous system development. Cross-sectional data suggest gut microbiota of individuals with and without attention deficit hyperactivity disorder (ADHD) differs. We hypothesized that infant gut microbiota composition is associated with later ADHD development in our on-going birth cohort study, WHEALS.

Methods

Gut microbiota was profiled using 16S ribosomal RNA and the internal transcribed spacer region 2 (ITS2) sequencing in stool samples from 1 month and 6 months of age. ADHD was defined by parent-reported or medical record doctor diagnosis at age 10.

Results

A total of 314 children had gut microbiota and ADHD data; 59 (18.8%) had ADHD. After covariate adjustment, bacterial phylogenetic diversity (p = 0.017) and bacterial composition (unweighted UniFrac p = 0.006, R2 = 0.9%) at age 6 months were associated with development of ADHD. At 1 month of age, 18 bacterial and 3 fungal OTUs were associated with ADHD development. At 6 months of age, 51 bacterial OTUs were associated with ADHD; 14 of the order Lactobacillales. Three fungal OTUs at 6 months of age were associated with ADHD development.

Conclusions

Infant gut microbiota is associated with ADHD development in pre-adolescents. Further studies replicating these findings and evaluating potential mechanisms of the association are needed.

Impact

  • Cross-sectional studies suggest that the gut microbiota of individuals with and without ADHD differs.

  • We found evidence that the bacterial gut microbiota of infants at 1 month and 6 months of age is associated with ADHD at age 10 years.

  • We also found novel evidence that the fungal gut microbiota in infancy (ages 1 month and 6 months) is associated with ADHD at age 10 years.

  • This study addresses a gap in the literature in providing longitudinal evidence for an association of the infant gut microbiota with later ADHD development.

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Fig. 1: Gut bacterial microbiota alpha diversity metrics at 1 and 6 months of age in children who later developed attention deficit hyperactivity disorder (ADHD) or were neurotypical (NT).
Fig. 2: Gut fungal microbiota alpha diversity metrics at 1 and 6 months of age in children who later developed attention deficit hyperactivity disorder (ADHD) or were neurotypical (NT).

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Funding

This study was supported by the National Institutes of Health (R01 AI050681, R01 HL113010, R01 HD082147, and P01 AI089473) and the Fund for Henry Ford Hospital. The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Author information

Authors and Affiliations

  1. Department of Public Health Sciences, Henry Ford Hospital, Detroit, MI, USA

    Andrea E. Cassidy-Bushrow, Alexandra R. Sitarik, Christine Cole Johnson, Zeinab Kassem, Albert M. Levin, Ganesa Wegienka & Jennifer K. Straughen

  2. Center for Urban Responses to Environmental Stressors, Wayne State University, Detroit, MI, USA

    Andrea E. Cassidy-Bushrow, Christine Cole Johnson, Ganesa Wegienka & Jennifer K. Straughen

  3. Department of Pediatrics, Henry Ford Hospital, Detroit, MI, USA

    Tisa M. Johnson-Hooper

  4. Center for Autism and Developmental Disabilities, Henry Ford Hospital, Detroit, MI, USA

    Tisa M. Johnson-Hooper & Jannel M. Phillips

  5. Department of Medicine, University of California, San Francisco, CA, USA

    Susan V. Lynch & Germaine J. M. Yong

  6. Division of Allergy and Clinical Immunology, Department of Pediatrics, Augusta University, Augusta, GA, USA

    Dennis R. Ownby

  7. Department of Psychiatry and Behavioral Health Services, Division of Neuropsychology, Henry Ford Hospital, Detroit, MI, USA

    Jannel M. Phillips

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  1. Andrea E. Cassidy-Bushrow
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Contributions

All authors provided substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data, in drafting and/or revising critically the article for important intellectual content; and in the final approval of the version to be published.

Corresponding author

Correspondence to Andrea E. Cassidy-Bushrow.

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Competing interests

S.V.L. is a board member and consultant for Siolta Therapeutics Inc. All other authors declare no conflict of interest.

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Parental written informed consent and pre-adolescent written informed assent were obtained for the conduct of the study. Specific patient consent was not required for the current manuscript.

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Cassidy-Bushrow, A.E., Sitarik, A.R., Johnson, C.C. et al. Early-life gut microbiota and attention deficit hyperactivity disorder in preadolescents. Pediatr Res 93, 2051–2060 (2023). https://doi.org/10.1038/s41390-022-02051-6

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