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

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.