Jingning formula alleviates ADHD by restoring gut microbiota dysbiosis and tryptophan metabolic dysfunction

Jingning Fang (JNF), a clinically used herbal medicine for attention deficit hyperactivity disorder (ADHD), demonstrates significant efficacy in alleviating core symptoms such as hyperactivity and impulsivity in pediatric patients. To systematically investigate its therapeutic mechanisms, we implemented an integrated approach encompassing UPLC-Q-TOF/MS-based untargeted metabolomics profiling of brain, serum, and fecal specimens, targeted quantification of tryptophan pathway metabolites across these biological compartments, and gut microbiome characterization via 16S rRNA sequencing. Our analysis revealed a prominently dysregulated metabolic pathway in ADHD, characterized by perturbations in tryptophan metabolism that were particularly pronounced in feces (P < 0.05). Notably, the kynurenic acid (KYNA)/quinolinic acid (QUINA) ratio, a pivotal indicator of kynurenine pathway homeostasis, exhibited robust correlations with both behavioral manifestations and gut microbial ecology. These findings provide a mechanistic basis for JNF's clinical efficacy in ADHD management by highlighting its role in restoring gut microbiome balance and tryptophan metabolic homeostasis.