Heavy metals, noradrenaline/adrenaline ratio, and microbiome-associated hormone precursor metabolites: biomarkers for social behaviour, ADHD symptoms, and executive function in children

The gut microbiome significantly influences physical and mental health, including the synthesis and metabolism of hormones and the detoxification of heavy metals, which are linked to behavioural disorders. This study investigated the associations of these biological factors with the behaviour of primary school children, specifically examining the effects of heavy metals, catecholamines, and microbiome-associated metabolites of dopamine, noradrenaline, adrenaline, and thyroxine precursors. Urine samples from 87 unselected primary school children were analysed to assess heavy metal load (arsenic, cadmium, lead, mercury), noradrenaline/adrenaline ratio, and microbiome-associated metabolites of phenylalanine, tyrosine and L-dopa (3-phenylpropionic acid, p-OH-phenylacetic acid, 4-hydroxybenzoic acid, 3,4-dihydroxyphenylpropionic acid). Three months later, executive functions, ADHD symptoms (inattention, hyperactivity and impulsivity), and social behaviour were evaluated via parent and teacher questionnaires. In a path model, heavy metal load, microbiome-associated metabolites, and the noradrenaline/adrenaline ratio measured in urine accounted for 32% of social behaviours. Microbiome-associated metabolites predicted 11% of the variance in executive functions and 17% in ADHD symptoms. Executive functions shared 55% of the variance with ADHD symptoms and 17% with social behaviours. Children with the lowest social behaviours had a sixfold increase in the odds of high heavy metal loads and a 3.4-fold increase in the odds of elevated microbiome-associated metabolites. Similarly, children with the most compromised executive functions had a threefold increase in the odds of such high metabolite levels. Overall, the results indicate that children's social behaviours are influenced by heavy metal accumulation, catecholamine balance, and the microbiome-associated metabolism of amino acids, that are crucial for producing stress and thyroid hormones.