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

Micronutrients have demonstrated promise in managing inattention and emotional dysregulation in children with attention-deficit/hyperactivity disorder (ADHD). One plausible pathway by which micronutrients improve symptoms is the gut microbiome. This study examines changes in fecal microbial composition and diversity after micronutrient supplementation in children with ADHD (<i>N</i> = 44) and highlights potential mechanisms responsible for the behavioral improvement, as determined by blinded clinician-rated global improvement response to micronutrients. Participants represent a sub-group of the Micronutrients for ADHD in Youth (MADDY) study, a double blind randomized controlled trial in which participants received micronutrients or placebo for 8 weeks, followed by an 8-week open extension. 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 investigated changes in fecal microbial composition between micronutrients versus placebo and responders versus non-responders. A significant change in microbial evenness, as measured by alpha diversity, and beta-diversity, as measured by Bray-Curtis, was observed following micronutrients supplementation. The phylum <i>Actinobacteriota</i> decreased in the micronutrients group compared to placebo. Two butyrate-producing bacterial families: <i>Rikenellaceae</i> and <i>Oscillospiraceae</i>, exhibited a significant increase in change following micronutrients between responders versus non-responders. These findings suggest that micronutrients modulated the composition of the fecal microbiota and identified specific bacterial changes associated with micronutrient responders.