Several studies have described in autistic patients an overgrowth of unusual gut bacterial strains, able to push the fermentation of tyrosine up to the formation of p-cresol. We compared levels of urinary p-cresol, measured by high-performance liquid chromatography-ultraviolet, in 59 matched case-control pairs. Urinary p-cresol was significantly elevated in autistic children smaller than 8 years of age (p < 0.01), typically females (p < 0.05), and more severely affected regardless of sex (p < 0.05). Urinary cotinine measurements excluded smoking-related hydrocarbon contaminations as contributors to these differences. Hence, elevated urinary p-cresol may serve as a biomarker of autism liability in small children, especially females and more severely affected males.

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.

Microbiota-gut brain axis involvement in neuropsychiatric disorders Background The microbiota-gut brain (MGB) axis is the bidirectional communication between the intestinal microbiota and the brain. An increasing body of preclinical and clinical evidence has revealed that the complex gut microbial ecosystem can affect neuropsychiatric health. However, there is still a need of further studies to elucidate the complex gene-environment interactions and the role of the MGB axis in neuropsychiatric diseases, with the aim of identifying biomarkers and new therapeutic targets, to allow early diagnosis and improving treatments. Areas covered To review the role of MGB axis in neuropsychiatric disorders, prediction and prevention of disease through exploitation, integration and combination of data from existing gut microbiome/microbiota projects and appropriate other International "-Omics" studies. We also evaluated the new technological advances to investigate the microbiome and evidence-based treatment modulating the gut microbiota through nutritional and other interventions. Expert Opinion The clinical studies have documented an association between alterations in gut microbiota composition and/or function, whereas the preclinical studies support a role for the gut microbiota in impacting behaviours which are of relevance to psychiatry and other central nervous system (CNS) disorders. Targeting MGB axis could be an additional approach for treating CNS disorders and all conditions in which alterations of the gut microbiota are involved.

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Aims.To study the potential use of child behaviour checklist (CBCL) 1.5–5 scales for the early identification of preschoolers at risk of autism.Methods.CBCL scores of three groups of preschoolers were compared: (1) an experimental group of 101 preschoolers with autism spectrum disorder (ASD); (2) a control group of 95 preschoolers with other psychiatric disorders (OPD); (3) a control group of 117 preschoolers with typical development (TD). One-way analysis of variance (ANOVA), logistic regression with odds ratio (OR) and receiver operating characteristic (ROC) analyses were performed.Results.ANOVA revealed that ASD and OPD had significantly higher scores in almost all CBCL scales than TD. ASD presented significantly higher scores than OPD on Withdrawn, Attention Problems and Pervasive Developmental Problems (PDP) scales. Logistic regression analysis demonstrated that these same CBCL scales have validity in predicting the presence of an ASD towards both TD and OPD. ROC analysis indicated high sensitivity and specificity for PDP (0.85 and 0.90) and Withdrawn (0.89 and 0.92) scales when ASD is compared to TD. Specificity (0.60 for PDP and 0.65 for Withdrawn) decreases when comparing ASD and OPDConclusions.The PDP and Withdrawn scales have a good predictive validity so that they could be proposed as a first-level tool to identify preschoolers at risk of autism in primary care settings. Problems regarding the lower specificity when comparing ASDv. OPD are discussed.

BackgroundA 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.MethodsA 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.DiscussionThe 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.Trial registrationClinicalTrials.gov Identifier: NCT02708901. Retrospectively registered: March 4, 2016.

This study investigated the prevalence and type of gastrointestinal (GI) and food selectivity (FS) symptoms in 163 preschoolers with ASD, and their possible links with core ASD features and emotional/behavioural problems. 40.5% of children with ASD had at least one severe GI symptom or FS. Preschoolers with and without GI symptoms and with and without FS were significantly different on several emotional/behavioural problems and restrictive/repetitive behaviours, whereas they did not differ significantly on performance IQ and autistic severity. The GI plus FS group presented with Sleep Problems, Self-injurious Behaviors and Anxiety Problems. Results indicated the need for early identification of GI disturbances and FS in order to design tailored intervention for these symptoms frequently associated to challenging behaviours in ASD.

BackgroundRecent investigations suggest a possible common genetic background between Autism Spectrum Disorders (ASD) and Celiac Disease (CD). However, studies regarding this association are scarce and often limited by the small sample sizes and/or large heterogeneity among ASD groups in terms of demographic and clinical features. The present study aims to investigate the overall CD prevalence (biopsy proven-CD patients plus screening detected tTG and EMA positive cases) in a large population of pre-schoolers with ASD referred to a tertiary care University Hospital.MethodsWe retrospectively collected data about 382 children (mean age: 46.97 ± 13.55 months; age-range: 18-72 months) consecutively diagnosed as ASD (according to the Diagnostic and Statistical Manual of Mental Disorders 4th edition criteria) over the period 2010–2013, and who performed a serological CD screening.ResultsThe overall CD prevalence was 2.62%, which is statistically significant higher to that reported in the Italian paediatric population (p = 0.0246). Half of these children had no symptoms or risk factors related to CD when they performed the serological screening.ConclusionsIf replicated, these data suggest the importance of regular screening for CD in young patients with ASD, and are of relevance for clinical and public health.