Effects of gut microbiota-derived metabolites on iPSC-derived dopaminergic neurons from individuals with ADHD

Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders, affecting more than 5% of children and adolescents worldwide and persisting into adulthood in approximately 60% of cases. Its etiology involves a complex interplay between genetic and environmental factors. Emerging evidence indicates altered gut microbiota composition in individuals with ADHD, while maternal dietary patterns during pregnancy have been associated with ADHD traits in offspring. Together, these findings suggest a potential involvement of the microbiota-gut-brain axis (MGBA) in ADHD pathophysiology. Oxidative stress, neuroinflammation, and dopaminergic dysregulation have also been implicated in the disorder.

Human induced pluripotent stem cell (iPSC)-derived neural models provide an opportunity to investigate these mechanisms while preserving the donors’ genetic backgrounds. Here, we investigated whether gut microbiota-derived metabolites modulate cell viability, oxidative stress, and neuroinflammatory markers in iPSC-derived dopaminergic neurons from individuals with ADHD and controls.

Our preliminary findings suggest that selected gut microbiota-derived metabolites might differentially modulate cell viability, reactive oxygen species levels, and the release of IL-6 and TNFα between groups. These findings may help identify ADHD-associated cellular phenotypes and elucidate how microbiota-derived metabolites influence dopaminergic neurons, providing a platform for investigating microbiota-related mechanisms and potential novel therapeutic strategies for ADHD.