Behavioural, cognitive, and neurophysiological effects of a synbiotic supplementation enriched with pigmented corn extract or cornstarch in drug-naïve children with attention-deficit hyperactivity disorder: A randomised, double-blind, comparison-controlled clinical trial.

Background & aims: Considerable interest has been recently given to the potential role of the gut-brain axis (GBA) -a two-way communication network between the gut microbiota and the central nervous system- in the pathogenesis of attention-deficit hyperactivity disorder (ADHD), suggesting the potential usefulness of probiotic and synbiotic supplementations. In light of the limited available evidence, synbiotic efficacy in ADHD children not taking medications should be clarified. This study aimed to investigate the efficacy of a synbiotic dietary supplementation on fatty acids levels as well as on microbiota composition, behaviour, cognition, and brain function in children with ADHD.

Methods: A total of 41 drug-naïve school-aged children diagnosed with ADHD were enrolled in a 3-month randomised, double-blind, comparison-controlled clinical trial, receiving either a synbiotic mix (COMP group) or the same synbiotic mix enriched with an additional extract from pigmented corn (EXP group). Changes in levels of some specific short-chain and branched-chain fatty acids were considered as primary outcomes. Secondary outcome measures included gut microbiota profiling, Child Behaviour Checklist, Conners Parent Rating Scale-revised, computerised cognitive tasks, and haemodynamic response to a Go-NoGo task measured by fNIRS.

Results: No superiority of the EXP synbiotic mix was observed. Analysis of fatty acids did not reveal any significant difference between groups. Children in the COMP group reported a slightly greater improvement than those in the EXP group in focused attention and in the haemodynamic response to a cognitive task.

Conclusions: This study shows that pigmented corn extract does not enhance the effects of the synbiotic supplementation in ADHD children in terms of fatty acid production, microbiota composition, clinical, cognitive and neurophysiological measures. However, a synbiotic mix of probiotics plus prebiotic acacia fibre and cornstarch could have some promising effects on ADHD symptoms, which warrants further research. Future studies should also continue to explore the potential of fNIRS for monitoring the effects of interventions that target the GBA.

Trial registration: ClinicalTrials.gov: NCT06005506.