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Effect of Probiotic Supplementation on Behavioral and Gastrointestinal Symptoms in Autism Spectrum Disorders: A Randomized Double Blind, Placebo-Controlled Trial
Recent open studies have shown some promising results of probiotic supplementation in ASD on gastrointestinal (GI) symptoms, reporting also significant changes in behavioural symptoms. To date only one study was carried out as a randomized placebo controlled trial but it was affected by a high drop-out rate and other methodological limitations.
Therefore, efficacy of probiotics in patients with ASD remains undefined.
Objectives:
The main aim of this study is to determine the effects of a 6 months supplementation with a probiotic preparation in preschoolers with ASD on behavioral and GI symptoms.
Methods:
Eighty-five children with ASD (age-range: 2.18-6.11 years; mean ± DS: 4.15 ± 1.08 years) diagnosed according to DSM-5 criteria, were included in this randomized double-blind randomized controlled trial (funded by the Italian Ministry of Health, grant GR-2011-02348280). Methodology was reported in Santocchi et al. 2016 (DOI 10.1186/s12888-016-0887-5) and in ClinicalTrials.gov (NCT02708901).
At baseline each subject was classified as belonging to the Gastro-Intestinal (GI) group or to the Non-GI (NGI) group on the basis of the presence of significant GI symptoms measured through the Gastrointestinal Severity Index (GI Severity Index) (cut-off = 4.0).
ASD participants belonging to the two groups (30 subjects for GI group and 55 for NGI group) were blindly randomized 1:1 to regular diet with probiotics or with placebo for 6 months-treatment. The probiotic preparation selected for this study is Vivomixx®, a multicomponent product containing 450 billions of lyophilized bacterial cells belonging to eight probiotic strains: one strain of Streptococcus thermophilus, three strains of Bifidobacterium and four strains of Lactobacillus. Vivomixx® is a patented and marketed product and it has been approved for the use in children. The primary end point of the trial was the reduction in ADOS total composite score (TCS).
Results:
Sixty-three subjects (74%; 17 subjects for GI group and 46 for NGI group) completed the treatment follow-up; no significant difference between the dropout rates was observed in the two treatment groups. The placebo and probiotic groups resulted to be homogeneous at baseline with regard to all prognostic variables.
The two treatments showed a very good tolerability profile, with negligible and similar adverse event rates.
The mean difference between ADOS at baseline and post treatment TCS values resulted to be +0.03 in placebo group and -0.65 in probiotic group (p= 0.91 vs P= 0.02 respectively). The ADOS mean change in the probiotic group was not affected by the presence of GI symptoms. In fact, this value resulted -0.81 in subgroup without GI symptoms in comparison with -0.22 in subgroup with GI symptoms. The mean improvement in GI Severity Index in probiotic group (-0.83) was significant (p= 0.04) at variance with the same in placebo group (mean improvement = -0.08; P= 0.90).
Conclusions:
Six-month treatment with probiotics at variance with placebo is significantly effective in reducing the severity of ASD. The response is not related to the presence of GI symptoms, which, incidentally, improve significantly in the probiotic group.