Tourette syndrome results from a complex interaction between social–environmental factors, multiple genetic abnormalities, and neurotransmitter disturbances. People with Tourette syndrome have an 85% lifetime prevalence of psychiatric comorbidities such as ADHD and OCD, followed by mood disorders, anxiety disorders, and disruptive behaviour disorders.
The therapeutic effect of antidopaminergic agents on Tourette symptoms supports the pathogenesis that neurotransmitters play an important role in Tourette syndrome. Probiotics are capable of altering the brain and behaviours of the host via the gut–brain axis (GBA). Studies examining the effects of probiotics and paediatric neurodevelopmental and neuropsychiatric diseases have been done but the contribution of gut microbiota to neurodevelopmental or neuropsychiatric diseases is complicated, with many influencing factors.
Hence, the authors of the current study felt more studies were needed to explore microbiome modulation as a possible intervention for paediatric neurodevelopment and neuropsychiatric diseases.
Probiotic PS128 has been demonstrated in animal studies to be a psychobiotic strain shown to modulate the levels of neurotransmitters in the brain, and increase concentrations of dopamine, serotonin, and their metabolites in the striatum. Moreover, in a recent randomised controlled trial studying the effects of PS128 on children with autistic spectrum disorder (ASD), the participants’ teachers observed a decrease in tic severity. A previous study on children with ASD, also found there was improvement in attention after treatment with PS128.
Therefore, the current double-blinded randomized-controlled trial was conducted at the National Taiwan University Children’s Hospital to test the hypothesis that PS128 may improve symptoms in children with Tourette syndrome and its comorbidities. This is the first clinical trial that has used probiotics in randomised, double-blind, and placebo-controlled settings to assess its effect on Tourette syndrome severity and its comorbidities.
A total of 58 participants, aged 5 to 18 and diagnosed with Tourette Syndrome, were enrolled from the children’s hospital between 2017 and 2019. Participants were allowed to continue their regular Tourette or ADHD medications but without alteration in medication and dosage during the trial. Participants were asked to refrain from consuming probiotic products during the two month study period.
Participants were randomly assigned to two groups in a 1:1 ratio. One group received Lactobacillus plantarum PS128 (provided by Bened Biomedical Co., Ltd.), and the other received a placebo that contained microcrystalline cellulose. The PS128 capsules contained 3 × 1010 CFU/capsule of PS128. Patients were assessed before the trial and at one and two months after randomisation.
The primary outcome, tic severity, was evaluated using the Yale Global Tic Severity Scale (YGTSS) through direct assessment by the experienced physician.
The secondary outcomes - assessed before and after the two-month trial - were the possible comorbidities in these children, including attention deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), migraine, and depression.
Probiotic impact on ADHD
The resulting data suggests that intervention with PS128 did not have a superior response in tic severity improvement compared to the control group. However, there was a significant improvement in some parameters of the most common comorbidity of Tourette syndrome patients, ADHD.
The CPT test was performed to evaluate the change in the parameters in ADHD and the team found that the intervention group showed improvement in commission t score and detectability parameters while the control group did not show any improvement.
Explaining the possible mechanism of action behind this finding, the team note that the pathophysiology behind selective attention involves the cholinergic and dopaminergic systems. Current evidence also suggests that ADHD symptoms may be caused by the reduction of two other neurotransmitters: norepinephrine and serotonin. There are known benefits of noradrenergic drugs in ADHD. As PS128 increases dopamine and serotonin levels in germ-free mice, an increase in brain dopamine might explain the findings in improved ADHD symptoms.
The authors argue that ADHD is as troubling, if not more, as tics in school learning. Although most children with Tourette syndrome do not need treatment due to mild symptoms, the severity of ADHD in these children may need medications to improve attention.
The authors conclude: "This study has demonstrated that probiotics PS128 does not affect children’s tic severity but improves ADHD symptoms. Our study demonstrates that two months of use of probiotics PS128 treatment improved Tourette children’s SNAP-IV (parent) and CPT scores. PS128 may be an appealing adjunctive therapy for Tourette children who have ADHD without adverse effects. Larger and longer trials should be done to fully understand the effect of probiotics on Tourette children’s behavior."
Wu, C.-C.; Wong, L.-C.; Hsu, C.-J.; Yang, C.-W.; Tsai, Y.-C.; Cheng, F.-S.; Hu, H.-Y.; Lee, W.-T.
"Randomized Controlled Trial of Probiotic PS128 in Children with Tourette Syndrome"
https://doi.org/10.3390/nu13113698 (registering DOI)