August 7, 2025
Journal Article

Gut microbiome changes with micronutrient supplementation in children with attention–deficit/hyperactivity disorder: the MADDY study

Abstract

Micronutrients have demonstrated promise in managing inattention and emotional dysregulation in children with attention-deficit/hyperactivity disorder (ADHD). The biological mechanism by which micronutrients improve these symptoms remains unclear. One plausible pathway is through the gut-brain axis, the bi-directional communication network that links the gastrointestinal tract with the brain. This study examines changes in gut microbiome composition and diversity after micronutrients supplementation in children with ADHD (N=44) and sheds light on potential mechanisms responsible for the response to micronutrients as measured by clinician-rated global impression. Participants from this investigation represent a sub-group of the Micronutrients for ADHD in Youth (MADDY) study, a double blind randomized controlled study in which participants received either micronutrients or a placebo for 8 weeks, followed by an 8-week open label extension with micronutrients for all participants. Stool samples collected at baseline, week 8, and week 16 were analyzed using 16S rRNA amplicon sequencing targeting the V4 hypervariable region. Pairwise compositional analyses served as the primary means for investigating changes in gut microbiome composition between micronutrients versus placebo groups and responders versus non-responders. A significant change in microbial evenness, as measured by alpha diversity, was observed following micronutrients, and the phylum Actinobacteriota decreased in the micronutrients group compared to placebo. Additionally, two bacterial families: Rikenellaceae and Oscillospiraceae, exhibited a significant increase in change of gut microbiome composition following micronutrients between responders and non-responders. These findings suggest that micronutrients modulated the composition of the gut microbiome and point towards specific bacterial changes associated with response to micronutrients.

Published: August 7, 2025

Citation

Ast H., M.J. Hammer, S. Zhang, A.M. Bruton, I. Hatsu, B. Leung, and R.S. McClure, et al. 2025. Gut microbiome changes with micronutrient supplementation in children with attention–deficit/hyperactivity disorder: the MADDY study. Gut Microbes 17, no. 1:Art. No. 2463570. PNNL-SA-200316. doi:10.1080/19490976.2025.2463570

Research topics