Gut to brain interaction in Autism Spectrum Disorders: a randomized controlled trial on the role of probiotics on clinical, biochemical and neurophysiological parameters.
A high prevalence of a variety of gastrointestinal (GI) symptoms is frequently reported in patients with Autism Spectrum Disorders (ASD). The GI disturbances in ASD might be linked to gut dysbiosis representing the observable phenotype of a "gut-brain axis" disruption. The exploitation of strategies which can restore normal gut microbiota and reduce the gut production and absorption of toxins, such as probiotics addition/supplementation in a diet, may represent a non-pharmacological option in the treatment of GI disturbances in ASD. The aim of this randomized controlled trial is to determine the effects of supplementation with a probiotic mixture (Vivomixx®) in ASD children not only on specific GI symptoms, but also on the core deficits of the disorder, on cognitive and language development, and on brain function and connectivity. An ancillary aim is to evaluate possible effects of probiotic supplementation on urinary concentrations of phthalates (chemical pollutants) which have been previously linked to ASD.



A group of 100 preschoolers with ASD will be classified as belonging to a GI group or to a Non-GI (NGI) group on the basis of a symptom severity index specific to GI disorders. In order to obtain four arms, subjects belonging to the two groups (GI and NGI) will be blind randomized 1:1 to regular diet with probiotics or with placebo for 6 months. All participants will be assessed at baseline, after three months and after six months from baseline in order to evaluate the possible changes in: (1) GI symptoms; (2) autism symptoms severity; (3) affective and behavioral comorbid symptoms; (4) plasmatic, urinary and fecal biomarkers related to abnormal intestinal function; (5) neurophysiological patterns.



The effects of treatments with probiotics on children with ASD need to be evaluated through rigorous controlled trials. Examining the impact of probiotics not only on clinical but also on neurophysiological patterns, the current trial sets out to provide new insights into the gut-brain connection in ASD patients. Moreover, results could add information to the relationship between phthalates levels, clinical features and neurophysiological patterns in ASD.



ClinicalTrials.gov Identifier: NCT02708901 . Retrospectively registered: March 4, 2016.
IRCCS Stella Maris Foundation, Viale del Tirreno 331, 56018, Calambrone, Pisa, Italy. e.santocchi@fsm.unipi.it.
Elisa
E
Santocchi
National Research Council, Institute of Clinical Physiology, Via Moruzzi 1, Pisa, 56124, Italy.
Letizia
L
Guiducci
IRCCS Stella Maris Foundation, Viale del Tirreno 331, 56018, Calambrone, Pisa, Italy.
Francesca
F
Fulceri
National Research Council, Institute of Clinical Physiology, Via Moruzzi 1, Pisa, 56124, Italy.|Department of Clinical and Experimental Medicine, University of Pisa, Via Savi, 10, 56126, Pisa, Italy.
Lucia
L
Billeci
National Research Council, Institute of Clinical Physiology, Via Moruzzi 1, Pisa, 56124, Italy.
Emma
E
Buzzigoli
IRCCS Stella Maris Foundation, Viale del Tirreno 331, 56018, Calambrone, Pisa, Italy.
Fabio
F
Apicella
IRCCS Stella Maris Foundation, Viale del Tirreno 331, 56018, Calambrone, Pisa, Italy.
Sara
S
Calderoni
Department of Autism Research, Villa Santa Maria Institute, Via IV Novembre 15 22038, Tavernerio, Italy.
Enzo
E
Grossi
National Research Council, Institute of Clinical Physiology, Via Moruzzi 1, Pisa, 56124, Italy.
Maria Aurora
MA
Morales
IRCCS Stella Maris Foundation, Viale del Tirreno 331, 56018, Calambrone, Pisa, Italy.|Department of Clinical and Experimental Medicine, University of Pisa, Via Savi, 10, 56126, Pisa, Italy.
Filippo
F
Muratori
D000067877:Autism Spectrum Disorder / Q000150:complications / Q000188:drug therapy* / Q000382:microbiology; D001921:Brain / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D015897:Comorbidity; D019587:Dietary Supplements; D005260:Female; D005767:Gastrointestinal Diseases / Q000150:complications / Q000188:drug therapy* / Q000382:microbiology; D000069196:Gastrointestinal Microbiome / Q000187:drug effects; D006801:Humans; D008297:Male; D015995:Prevalence; D019936:Probiotics / Q000627:therapeutic use*
Autism Spectrum Disorders (ASD); Endophenotype; Gut-brain axis; Phtalates; Probiotic Vivomixx®; Quantitative electroencephalography (QEEG)