1. Introduction
Attention deficit hyperactivity disorder, ADHD, attention deficit hyperactivity disorder
SECONDARY
Synbiotic 2000, a pre + probiotic, reduced comorbid autistic traits and emotion dysregulation in attention deficit hyperactivity disorder (ADHD) patients. Immune activity and bacteria-derived short-chain fatty acids (SCFAs) are microbiota–gut–brain axis mediators. The aim was to investigate Synbiotic 2000 effects on plasma levels of immune activity markers and SCFAs in children and adults with ADHD. ADHD patients (n = 182) completed the 9-week intervention with Synbiotic 2000 or placebo and 156 provided blood samples. Healthy adult controls (n = 57) provided baseline samples. At baseline, adults with ADHD had higher pro-inflammatory sICAM-1 and sVCAM-1 and lower SCFA levels than controls. Children with ADHD had higher baseline sICAM-1, sVCAM-1, IL-12/IL-23p40, IL-2Rα, and lower formic, acetic, and propionic acid levels than adults with ADHD. sICAM-1, sVCAM-1, and propionic acid levels were more abnormal in children on medication. Synbiotic 2000, compared to placebo, reduced IL-12/IL-23p40 and sICAM-1 and increased propionic acid levels in children on medication. SCFAs correlated negatively with sICAM-1 and sVCAM-1. Preliminary human aortic smooth-muscle-cell experiments indicated that SCFAs protected against IL-1β-induced ICAM-1 expression. These findings suggest that treatment with Synbiotic 2000 reduces IL12/IL-23p40 and sICAM-1 and increases propionic acid levels in children with ADHD. Propionic acid, together with formic and acetic acid, may contribute to the lowering of the higher-than-normal sICAM-1 levels.Attention deficit hyperactivity disorder (ADHD) is a common childhood-onset neurodevelopmental psychiatric disorder with about 5% worldwide prevalence among children and adolescents and 3% in adults [Preclinical studies from germ-free and antibiotic drug-treated mouse models have shown that the absence or alteration of normal gut microbiota early in life has significant effects on immune activity [Short-chain fatty acids (SCFAs) have been proposed to be messengers for microbiota–gut–brain communication. They are fatty acids with less than six carbon atoms, which are mainly generated by anaerobic colonic bacteria via fermentation of dietary fibers or branched-chain amino acids [Immune activity is also considered to be an important mediator in the microbiota–gut–brain axis [The aim of this study was to explore the effects of Synbiotic 2000 on concentrations of plasma immune activity markers and SCFAs in ADHD. These analyte concentrations constitute secondary outcome measures in the placebo-controlled randomized trial ISRCTN57795429 (