Treating impulsivity with probiotics in adults (PROBIA): study protocol of a multicenter, double-blind, randomized, placebo-controlled trial

Abstract

Background: Impulsivity and compulsivity are related to emotional and social maladjustment and often underlie psychiatric disorders. Recently, alterations in microbiota composition have been shown to have implications for brain development and social behavior via the microbiota-gut-brain axis. However, the exact mechanisms are not fully identified. Recent evidence suggests the modulatory effect of synbiotics on gut microbiota and the contribution of these agents in ameliorating symptoms of many psychiatric diseases. To date, no randomized controlled trial has been performed to establish the feasibility and efficacy of this intervention targeting the reduction of impulsivity and compulsivity. We hypothesize that supplementation with synbiotics may be an effective treatment in adults with high levels of impulsivity and/or compulsivity. Methods/design: This is a prospective, multicenter, double-blind, randomized controlled trial with two arms: treatment with a synbiotic formula versus placebo treatment. The primary outcome is the response rate at the end of the placebocontrolled phase (response defined as a Clinical Global Impression-Improvement Scale score of 1 or 2 = very much improved or much improved, plus a reduction in the Affective Reactivity Index total score of at least 30% compared with baseline). A total of 180 participants with highly impulsive behavior and a diagnosis of attention deficit/hyperactivity disorder (ADHD) and/or borderline personality disorder, aged 18-65 years old, will be screened at three study centers. Secondary outcome measures, including changes in general psychopathology, ADHD symptoms, neurocognitive function, somatic parameters, physical activity, nutritional intake, and health-related quality of life, will be explored at assessments before, during, and at the end of the intervention. The effect of the intervention on genetics, microbiota, and several blood biomarkers will also be assessed. Gastrointestinal symptoms and somatic complaints will additionally be explored at 1-week follow-up. Discussion: This is the first randomized controlled trial to determine the effects of supplementation with synbiotics on reducing impulsive and compulsive behavior. This clinical trial can contribute to explaining the mechanisms involved in the crosstalk between the intestinal microbiome and the brain. If effects can be established by reducing impulsive and compulsive behavior, new cost-effective treatments might become available to these patients.

Dietary interventions, the gut microbiome, and aggressive behavior: Review of research evidence and potential next steps

“…The authors found the incidence of these neuropsychiatric disorders to be 17% in the control group of 35 children and zero in the experimental group of 40 children who received the early probiotic intervention (with about half of the sample lost to attrition during the long follow‐up period). Interestingly, one of the first double‐blind, randomized, placebo‐controlled research projects has recently been launched to test the effects of probiotics on impulsivity in adults with ADHD (Arteaga‐Henriquez et al, 2020).…”

“…Thus, given the evidence presented above that the gut–brain axis likely plays a role in determining aggressive behavior (Sherwin et al, 2019; Sylvia et al, 2019) and that dietary supplementation is one of the most effective ways to influence the microbiome (Carmody et al, 2015; Gentile & Weir, 2018; Zmora et al, 2019), it may be surprising that so few studies test this relationship in humans (the rare exceptions are Arteaga‐Henríquez et al, 2020; Gao et al, 2019; Kato‐Kataoka et al, 2016). Part of the reason for this scarcity of studies must be the fact that the market of probiotics and prebiotics is diverse and largely unregulated (Quigley, 2019), due to the status of being “not quite a medicine.”…”

Exposure to Antibiotics and Neurodevelopmental Disorders: Could Probiotics Modulate the Gut–Brain Axis?

“…Interestingly, in 2019 a promising multinational clinical trial has been started to evaluate the effect of the administration of a symbiotic formula (Synbiotic 2000 Forte 400) containing a mixture of different probiotics ( Pediococcus pentosaceus , Lactobacillus paracasei subsp. Paracasei , L. plantarum , and Leuconostoc mesenteroides ) and four prebiotics (β-glucan, inulin, pectin, and resistant starch) in a cohort of 180 adults with ADHD [ 219 ]. To date, clinical studies applying probiotics in ADHD patients are still limited and future studies are needed to achieve sufficient evidence to recommend probiotics administration as beneficial treatment in ADHD.…”

Beyin ve Bağırsak Mikrobiyotası Arasındaki İlişkinin Bilişsel Duygusal Davranışsal ve Fizyolojik Açıdan Değerlendirilmesi

“…In this respect, some contributions are expected in the contexts of cognition, emotion and behavior by using probiotic supplements. Some studies suggested that probiotic supplementation in adults was used for the effective treatment of impulsivity, which is the underlying mechanism of certain psychiatric disorders or problem behaviors (Arteaga-Henríquez et al 2020). It is thought that probiotics have important contributions not only in impulsivity but also in the above-mentioned mechanisms.…”