Randomized Double-Blind Crossover Study for Evaluating a Probiotic Mixture on Gastrointestinal and Behavioral Symptoms of Autistic Children

Cristina Guidetti; Elena Salvini; Maurizio Viri; Francesca Deidda; Angela Amoruso; Annalisa Visciglia; Lorenzo Drago; Matteo Calgaro; Nicola Vitulo; Marco Pane; Anna Claudia Caucino

doi:10.3390/jcm11185263

Randomized Double-Blind Crossover Study for Evaluating a Probiotic Mixture on Gastrointestinal and Behavioral Symptoms of Autistic Children

J Clin Med. 2022 Sep 6;11(18):5263. doi: 10.3390/jcm11185263.

Affiliations

¹ Department of Child Neuropsychiatry, University Hospital Maggiore della Carità, 28100 Novara, Italy.
² Probiotical Research Srl, Via E. Mattei 3, 28100 Novara, Italy.
³ Department of Biomedical Sciences for Health, University of Milan, 20133 Milan, Italy.
⁴ Department of Biotechnology, University of Verona, 37100 Verona, Italy.

Abstract

Autism spectrum disorders (ASDs) represent a diagnostic challenge with a still partially uncertain etiology, in which genetic and environmental factors have now been assessed. Among the hypotheses underlying the involvement of biological and environmental factors, the gut-brain axis is of particular interest in autism spectrum disorders. Several studies have highlighted the related incidence of particular gastrointestinal symptoms (GISs) in children suffering from ASDs. Probiotics have shown success in treating several gastrointestinal dysbiotic disorders; therefore, it is plausible to investigate whether they can alleviate behavioral symptoms as well. On these bases, a randomized double-blind crossover study with a placebo was conducted, evaluating the effects of a mixture of probiotics in a group of 61 subjects aged between 24 months and 16 years old with a diagnosis of ASD. Behavioral evaluation was performed through the administration of a questionnaire including a Parenting Stress Index (PSI) test and the Vineland Adaptive Behavior Scale (VABS). The Psycho-Educational Profile and the Autism Spectrum Rating Scale (ASRS) were also evaluated. Microbial composition analyses of fecal samples of the two groups was also performed. The study showed significant improvements in GISs, communication skills, maladaptive behaviors, and perceived parental stress level after the administration of probiotics. Microbiome alpha diversity was comparable between treatment arms and no significant differences were found, although beta diversity results were significantly different in the treatment group between T0 and T1 time points. Streptococcus thermophilus, Bifidobacterium longum, Limosilactobacillus fermentum, and Ligilactobacillus salivarius species were identified as some of the most discriminant taxa positively associated with T1 samples. This preliminary study corroborates the relationship between intestinal microbiota and ASD recently described in the literature.

Keywords: ASD; autism spectrum disorder; autistic children; behavioral symptoms; gastrointestinal symptoms; gut–brain axis; microbiome analysis; microbiota; probiotics; randomized double-blind crossover study.

Grants and funding

No funding. The supply of probiotics for the clinical trial was provided free of charge by the Probiotical Spa, Novara Italy. At the end of the clinical study, Probiotical supports the cost of reagents for Microbiome analysis and the editing of manuscript as well.