Prevalence and clinical features of celiac disease in a cohort of italian children with autism spectrum disorders

Background: Autism spectrum disorders (ASD) are a heterogeneous group of neurodevelopmental conditions whose etiopathogenesis derives from a complex interaction between genetic liability and environmental factors. In this framework, mounting evidence suggests that immune system dysfunction could be a risk factor contributing to the development of ASD in at least a subpopulation of individuals. In particular, some studies suggest an association between celiac disease (CD)—a long‐term autoimmune disorder that primarily affects the small intestine triggered by the ingestion of gluten—and ASD, while others hypothesized a random link. This investigation aimed to evaluate the prevalence of CD in a large sample of school‐aged children with ASD and to characterize their clinical profile. Methods: Medical records of 405 children with ASD aged 5–11 years (mean age: 7.2 years; SD: 1.8 years) consecutively referred to a tertiary‐care university hospital between January 2014 and December 2018 were reviewed; among them, 362 had carried out serological testing for CD. Results: Nine patients with positive CD serology were identified, eight of which satisfied the criteria for CD diagnosis. The estimated CD prevalence in ASD children was 2.18% (95% CI, 0.8–3.7), which was not statistically different (1.58%; p = 0.36) from that of an Italian population, matched for age range, considered as a control group (95% CI, 1.26–1.90). Three out of the eight ASD patients with CD did not have any symptoms suggestive of CD. Conclusions: Our findings did not show a higher prevalence of CD in ASD children than in the control population, but could suggest the utility of routine CD screening, given its frequent atypical clinical presentation in this population

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

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. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT02708901

Are fecal metabolome and microbiota profiles correlated with autism severity? A cross-sectional study on asd preschoolers

Autism spectrum disorders (ASD) make up a heterogeneous group of neurodevelopmental disorders characterized by social and communication difficulties associated with repetitive and restrictive behaviors. Besides core features, metabolic imbalances, inflammation, gastrointestinal (GI) symptoms, and altered gut microbiota composition were often described in association with ASD, but their connection with the severity of autism (SA) remains unexplored. In this study, fecal metabolome, microbiota, and calprotectin levels of 80 ASD preschoolers were quantified and correlated with SA. Twelve of the fifty-nine molecules that were quantified by fecal metabolome analysis were significantly associated with SA. No links between SA or GI symptoms and microorganisms’ relative abundance were highlighted. Significant correlations between bifidobacteria, Sutterella, lactobacilli relative abundance, and metabolomics profiles were found. These results suggest that fecal metabolome discriminates the SA and intestinal microorganisms mediate the link between metabolome and SA regardless of GI symptomatology. The study raises the possibility that grouping ASD populations through metabolomics and fecal microbiota could aid the identification of specific ASD endophenotypes, on the basis of the SA. Mechanistic studies focusing on detected biomarkers might be an option for future studies

Interventions on Microbiota: Where Do We Stand on a Gut– Brain Link in Autism? A Systematic Review

The alteration of the microbiota–gut–brain axis has been recently recognized as a critical modulator of neuropsychiatric health and a possible factor in the etiopathogenesis of autism spectrum disorders (ASD). This systematic review offers practitioners an overview of the potential therapeutic options to modify dysbiosis, GI symptoms, and ASD severity by modulating the microbiota–gut–brain axis in ASD, taking into consideration limits and benefits from current findings. Comprehensive searches of PubMed, Scopus, the Web of Science Core Collection, and EMBASE were performed from 2000 to 2021, crossing terms referred to ASD and treatments acting on the microbiota–gut–brain axis. A total of 1769 publications were identified, of which 19 articles met the inclusion criteria. Data were extracted independently by two reviewers using a preconstructed form. Despite the encouraging findings, considering the variability of the treatments, the samples size, the duration of treatment, and the tools used to evaluate the outcome of the examined trials, these results are still partial. They do not allow to establish a conclusive beneficial effect of probiotics and other interventions on the symptoms of ASD. In particular, the optimal species, subspecies, and dosages have yet to be identified. Considering the heterogeneity of ASD, double‐blind, randomized, controlled trials and treatment tailored to ASD characteristics and host‐microbiota are recommended

Inflammatory biomarkers are correlated with some forms of regressive autism spectrum disorder

Background: Several studies have tried to investigate the role of inflammatory biomarkers in Autism Spectrum Disorder (ASD), and their correlations with clinical phenotypes. Despite the growing research in this topic, existing data are mostly contradictory. Methods: Eighty-five ASD preschoolers were assessed for developmental level, adaptive functioning, gastrointestinal (GI), socio-communicative and psychopathological symptoms. Plasma levels of leptin, resistin, plasminogen activator inhibitor-1 (PAI-1), macrophage chemoattractant protein-1 (CCL2), tumor necrosis factor-alfa (TNF-α), and interleukin-6 (IL-6) were correlated with clinical scores and were compared among different ASD subgroups according to the presence or absence of: (i) GI symptoms, (ii) regressive onset of autism. Results: Proinflammatory cytokines (TNF-α, IL-6 and CCL2) were lower than those reported in previous studies in children with systemic inflammatory conditions. GI symptoms were not correlated with levels of inflammatory biomarkers except for resistin that was lower in ASD-GI children (p = 0.032). Resistin and PAI-1 levels were significantly higher in the group with “regression plus a developmental delay” onset (Reg+DD group) compared to groups without regression or with regression without a developmental delay (p < 0.01 for all). Conclusions: Our results did not highlight the presence of any systemic inflammatory state in ASD subjects neither disentangling children with/without GI symptoms. The Reg + DD group significantly differed from others in some plasmatic values, but these differences failed to discriminate the subgroups as possible distinct ASD endo-phenotypes