Microbiome signatures correlate with diet-mediated ADHD symptom reduction

Attention-deficit hyperactivity disorder (ADHD) is one of the most common childhood neuropsychiatric conditions. Both (epi)genetic and environmental factors are suggested to contribute to the aetiology of ADHD. In the last decade, nutrition has received considerable attention as potential environmental factor triggering ADHD behaviour, particularly applying a few-foods diet (FFD) has been shown to elicit considerable behavioural improvements. In the present study 79 children with ADHD followed a (progressive) FFD diet for 5 weeks, demonstrating that 63% of the participating children showed a more than 40% behaviour score improvement, with an average improvement of 73%. Minimally invasive samples (faeces, urine, blood and buccal swab) were collected before and after the intervention to obtain a multi-omics perspective of the dietary responses in the participating children. Integrated analysis of all omics data collected confirmed the children's compliance to the FFD intervention by conserved diet-induced microbiome and metabolome changes. However, these analysis did not reveal multi-omics signatures that were associated to the diet-induced ADHD symptom changes in the children. Nevertheless, the behaviour changes were significantly correlated with gut-microbiome composition, which was especially apparent when applying species-stratified abundance values of the previously defined gut-brain modules in the faecal metagenomic data. Moreover, these microbiome signatures also correlated with previously reported FFD-induced activation of the praecuneus region in the brain of children displaying significant behaviour improvements. These findings implicate an important role of the gut-microbiome and capacity to communicate with the central nervous system in FFD-mediated ADHD symptom reduction in children with food-associated ADHD.