Effects of Probiotic Supplementation on Gastrointestinal, Sensory and Core Symptoms in Autism Spectrum Disorders: A Randomized Controlled Trial

Abstract

The microbiota-gut-brain axis has been recently recognized as a key modulator of neuropsychiatric health. In this framework, probiotics (recently named "psychobiotics") may modulate brain activity and function, possibly improving the behavioral profiles of children with Autism Spectrum Disorder (ASD). We evaluated the effects of probiotics on autism in a double-blind randomized, placebo-controlled trial of 85 preschoolers with ASD (mean age, 4.2 years; 84% boys). Participants were randomly assigned to probiotics (De Simone Formulation) (n=42) or placebo (n=43) for six months. Sixty-three (74%) children completed the trial. No differences between groups were detected on the primary outcome measure, the Total Autism Diagnostic Observation Schedule-Calibrated Severity Score (ADOS-CSS). An exploratory secondary analysis on subgroups of children with or without Gastrointestinal Symptoms (GI group, n= 30; NGI group, n=55) revealed in the NGI group treated with probiotics a significant decline in ADOS scores as compared to that in the placebo group, with a mean reduction of 0.81 in Total ADOS CSS and of 1.14 in Social-Affect ADOS CSS over six months. In the GI group treated with probiotics we found greater improvements in some GI symptoms, adaptive functioning, and sensory profiles than in the GI group treated with placebo. These results suggest potentially positive effects of probiotics on core autism symptoms in a subset of ASD children independent of the specific intermediation of the probiotic effect on GI symptoms. Further studies are warranted to replicate and extend these promising findings on a wider population with subsets of ASD patients which share targets of intervention on the microbiota-gut-brain axis.

Probiotics, prebiotics, synbiotics, and fecal microbiota transplantation in the treatment of behavioral symptoms of autism spectrum disorder: A systematic review

“…Ten of them provided information on sex ratio of subjects with ASD (predominantly male). Most studies ( n = 10) documented the presence of at least one comorbid condition in their study cohort, primarily GI symptoms (Arnold et al, 2019; Grimaldi et al, 2018; Inoue et al, 2019; Kang et al, 2017; Niu et al, 2019; Sanctuary et al, 2019; Santocchi et al, 2020; Shaaban et al, 2018; Wang et al, 2020; West et al, 2013). Only five studies monitored participant compliance (Arnold et al, 2019; Grimaldi et al, 2018; Sanctuary et al, 2019; Santocchi et al, 2020; Shaaban et al, 2018), of which three reported their assessment results (high compliance rates [> 90%]) (Arnold et al, 2019; Sanctuary et al, 2019; Santocchi et al, 2020).…”

“…The selected articles reported on 13 different interventional studies that examined the use of microbial‐based therapies for the treatment of children with ASD. Eight probiotic trials were identified, of which two evaluated the effect of administering a single probiotic strain (Liu, Liong, et al, 2019; Parracho et al, 2010), while six investigated multiple probiotic strains in combination (Arnold et al, 2019; Liu, Liong, et al, 2019; Santocchi et al, 2020; Shaaban et al, 2018; Tharawadeephimuk et al, 2019; West et al, 2013). These interventions were primarily Bifidobacterium , Lactobacillus , and Lacticaseibacillus based; the most commonly tested strains were Bifidobacterium longum ( n = 5) and Lactobacillus acidophilus ( n = 4).…”

“…Notably, two RCTs had high dropout rates (72.6% and 36.6%, respectively) and did not adjust for an attrition bias in their analyses, which might give rise to considerable problems concerning the generalizability of results obtained (Grimaldi et al, 2018; Parracho et al, 2010). Only three RCTs scored a low risk of bias in all domains (Liu, Liong, et al, 2019; Sanctuary et al, 2019; Santocchi et al, 2020).…”

Paving the Way toward Personalized Medicine: Current Advances and Challenges in Multi-OMICS Approach in Autism Spectrum Disorder for Biomarkers Discovery and Patient Stratification

“…Interestingly, a specific species of Bacteroidetes called Bacteroidetes fragilis (B. fragilis) was shown to improve gut integrity and reduce ASD behavioral symptoms such as anxiety and repetitive behavior when it was administrated in ASD induced mice [ 123 ]. The administration of probiotics seems to be beneficial for ASD patients, as it has been explored in clinical trials (NCT02708901), and it showed a positive impact on ASD core symptoms in a subset of ASD patients [ 124 ].…”

Critical review on role of Microbiota transfer therapy in Autism spectrum disorder

“…The ef icacy of probiotics as a treatment option to suppress GI symptoms in ASD affected individuals was demonstrated through a randomized controlled study by Santocchi et al (2020). The study involved 85 participants diagnosed with ASD, who were randomly given probiotic or placebo mixture for six months.…”