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The Promising Role of Probiotics in Managing the Altered Gut in Autism Spectrum Disorders.

ABSTRACT: Gastrointestinal symptoms (GIS) have been reported repeatedly in people with autism spectrum disorder (ASD) and studies have reported interesting correlations between severity of behavioral and gastrointestinal symptoms. Growing evidence indicates that the gut microbiota in ASD is altered with various shifts described at different taxonomic levels, pointing to the importance of considering the gut-brain axis in treatment of these disorders. Probiotics are live beneficial bacteria that are ingested as food or customized pills. These beneficial bacteria, when added in sufficient amounts, can correct the dysbiosis. Because probiotics have shown success in treating irritable bowel syndrome (IBS), it is plausible to investigate whether they can induce alleviation of behavioral symptoms as well. Probiotics show, in some clinical studies, their potential benefits (1) in improving gastrointestinal dysfunction, (2) in correcting dysbiosis, (3) in consequently reducing the severity of ASD symptoms. This review compiles data from selected studies that investigate these benefits and the mechanisms that mediate these effects, which include the production of metabolites, hormones, and neurotransmitters and the regulation of pro-inflammatory and regulatory cytokines. Future research based on more randomized, controlled studies with a larger population size and standardized use of strains, concentration of probiotics, duration of treatments, and methods of DNA extraction is still needed in this area, which may lead to more robust results.

SUBMITTER: Abdellatif B

PROVIDER: S-EPMC7312735 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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The Promising Role of Probiotics in Managing the Altered Gut in Autism Spectrum Disorders.

Abdellatif Basma B McVeigh Clare C Bendriss Ghizlane G Chaari Ali A

International journal of molecular sciences 20200610 11

Gastrointestinal symptoms (GIS) have been reported repeatedly in people with autism spectrum disorder (ASD) and studies have reported interesting correlations between severity of behavioral and gastrointestinal symptoms. Growing evidence indicates that the gut microbiota in ASD is altered with various shifts described at different taxonomic levels, pointing to the importance of considering the gut-brain axis in treatment of these disorders. Probiotics are live beneficial bacteria that are ingest ...[more]

PMID: 32532137

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Project description: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.

Project description:BackgroundAutism spectrum disorder (ASD) is a type of neurodevelopmental disease that is frequently accompanied by sleep disorder. Herein, we investigated changes in the gut microbiota and its metabolites correlated with core symptoms and sleep problems in children with ASD.MethodsOne hundred and twenty children diagnosed with ASD based on Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria were enrolled in our study. The Autism Behavior Checklist (ABC), Social Responsiveness Scale (SRS), and Childhood Autism Rating Scale (CARS) were used to assess autism symptoms, and the Children Sleep Habits Questionnaire (CSHQ) was employed to evaluate sleep problems in children with ASD. The 120 children were divided into a sleep disorder group (n = 60) and a control group without sleep disorder (n = 60) according to the CSHQ answers. Illumina MiSeq analysis of 16S rRNA genes was used to compare differences in gut microbiota, and metabolomics analysis was employed to asses associated metabolites.ResultsSRS and CARS scores for the sleep disorder group were significantly higher than for the control group (p < 0.05). The abundances of butyrate-producing bacteria Faecalibacterium and Agathobacter were reduced significantly in the sleep disorder group (p < 0.05), and this was negatively correlated with CSHQ score (p = 0.007 and p = 0.014, respectively). The abundance of Agathobacter was also negatively associated with the ABC language score (p = 0.044). Furthermore, levels of 3-hydroxybutyric acid and melatonin were significantly lower (p < 0.05) while serotonin levels were higher (p < 0.05) in the sleep disorder group. The 3-hydroxybutyric acid level was positively associated with Faecalibacterium abundance (p = 0.000), and melatonin was positively associated with the abundance of Faecalibacterium (p = 0.036) and Agathobacter (p = 0.041). We also observed negative correlations between 3-hydroxybutyric acid and CSHQ (p = 0.000) and CARS (p = 0.009), between melatonin and CSHQ (p = 0.002) and ABC sensory score (p = 0.021), and a positive correlation between serotonin and CSHQ (p = 0.002) and ABC sensory score (p = 0.025).ConclusionsASD children with sleep disorder exhibited declines in the abundance of Faecalibacterium and Agathobacter, decreased levels of 3-hydroxybutyric acid and melatonin, and an increase in serotonin. These changes may aggravate sleep problems and core symptoms in children with ASD.

Project description:Autism spectrum disorders (ASD) affect 1% of children. Although there is no cure, early diagnosis and behavioral intervention can relieve the symptoms. The clinical heterogeneity of ASD has created a need for improved sensitive and specific laboratory diagnostic methods. Liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based analysis of the metabolome has shown great potential to uncover biomarkers for complex diseases such as ASD. Here, we used a two-step discovery-validation approach to identify potential novel metabolic biomarkers for ASD. Urine samples from 57 children with ASD and 81 matched children with typical development (TD) were analyzed by LS-MS/MS to assess differences in urinary amino acids and their metabolites (referred to as UAA indicators). A total of 63 UAA indicators were identified, of which 21 were present at significantly different levels in the urine of ASD children compared with TD children. Of these 21, the concentrations of 19 and 10 were higher and lower, respectively, in the urine of ASD children compared with TD children. Using support vector machine modeling and receiver operating characteristic curve analysis, we identified a panel of 7 UAA indicators that discriminated between the samples from ASD and TD children (lysine, 2-aminoisobutyric acid, 5-hydroxytryptamine, proline, aspartate, arginine/ornithine, and 4-hydroxyproline). Among the significantly changed pathways in ASD children were the ornithine/urea cycle (decreased levels of the excitatory amino acid aspartate [p = 2.15 × 10-10] and increased arginine/ornithine [p = 5.21 × 10-9]), tryptophan metabolism (increased levels of inhibitory 5-hydroxytryptamine p = 3.62 × 10-9), the methionine cycle (increased methionine sulfoxide [p = 1.46 × 10-10] and decreased homocysteine [p = 2.73 × 10-7]), and lysine metabolism (reduced lysine [p = 7.8 × 10-9], α-aminoadipic acid [p = 1.16 × 10-9], and 5-aminovaleric acid [p = 1.05 × 10-5]). Collectively, the data presented here identify a possible imbalance between excitatory and inhibitory amino acid metabolism in ASD children. The significantly altered UAA indicators could therefore be potential diagnostic biomarkers for ASD.

Dataset Information

The Promising Role of Probiotics in Managing the Altered Gut in Autism Spectrum Disorders.

Publications

The Promising Role of Probiotics in Managing the Altered Gut in Autism Spectrum Disorders.

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