Autism Spectrum Disorder and the Gut Microbiota in Children: A Systematic Review

Bezawada, Navya; Phang, Tze Hui; Hold, Georgina L.; Hansen, Richard

doi:10.1159/000505363

Cited by 70 publications

(42 citation statements)

References 71 publications

(233 reference statements)

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“…The etiopathogenesis of this complex and heterogeneous condition is attributable to early deviation in structural and functional brain development caused by interactions between several genetic and environmental factors, most of which are not yet determined. In recent years, neuroscience research has focused on the role of the microbiotabrain-gut axis in the etiopathogenesis of neurodevelopmental disorders including ASD, thus providing interesting targets for novel psychotropic development (2)(3)(4)(5)(6)(7)(8). The gut microbiota can impact brain function, both directly and indirectly, through the production of neurotransmitters, short-chain fatty acids (SCFAs) and key dietary amino acids and their metabolites, as well as through the activation of the immune system that, in turn, could act through inflammatory cytokines and chemokines, such as IL-6 and TNF-a.…”

Section: Introductionmentioning

confidence: 99%

“…The brain, in turn, modulates gut peristalsis, sensory and secretion function, through the vagus nerve. Gut microbiota perturbations can lead to alterations of all these pathways, thus contributing to the onset or the phenotypic expression of neuropsychiatric and neurodevelopmental disorders (2)(3)(4)(5)(6)(7)(8). The possible role of the gut microbiota in ASD has been conceptualized starting from several lines of evidence.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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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.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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“…Many studies have reported that ASD is associated with abnormal gut microbial metabolism [49][50][51]. Gut microbiota metabolites, including phenylalanine, tyrosine, hippurate and tryptophan, have been reported to be factors in the development of ASD [52][53][54][55].…”

Section: Discussionmentioning

confidence: 99%

Differential Metabolites in Chinese Autistic Children: A Multi-Centre Study Based on Urinary 1H-NMR Metabolomics Analysis

Zhou

et al. 2020

Preprint

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Background: Autism spectrum disorder (ASD) is a group of early-onset neurodevelopmental disorders. However, there is no valuable biomarker for the early diagnosis of ASD. Our large-scale and multi-centre study aims to identify metabolic variations between ASD and healthy children and to investigate differential metabolites and associated pathogenic mechanisms.Methods: 117 autistic children and 119 healthy children were recruited from research centres of 7 cities. Urine samples were assayed by 1H-NMR metabolomics analysis to detect metabolic variations. Multivariate statistical analysis, including principal component analysis (PCA) and orthogonal projection to latent structure discriminant analysis (OPLS-DA), as well as univariate analysis were used to assess differential metabolites between the ASD and control groups. The differential metabolites were further analysed by receiver operating characteristics (ROC) curve analysis and metabolic pathways analysis.Results: Compared with the control group, the ASD group showed higher levels of glycine, guanidinoacetic acid, creatine, hydroxyphenylacetylglycine, phenylacetylglycine and formate and lower levels of 3-aminoisobutanoic acid, alanine, taurine, creatinine, hypoxanthine and N-methylnicotinamide. ROC curve showed relatively significant diagnostic values for hypoxanthine (area under the curve (AUC) = 0.657, 95% CI 0.588 to 0.726), creatinine (AUC = 0.639, 95% CI 0.569 to 0.709), creatine (AUC = 0.623, 95% CI 0.552 to 0.694), N-methylnicotinamide (AUC = 0.595, 95% CI 0.523 to 0.668) and guanidinoacetic acid (AUC = 0.574, 95% CI 0.501 to 0.647) in the ASD group. Combining the metabolites creatine, creatinine and hypoxanthine, the AUC of the ROC curve reached 0.720 (95% CI 0.659 to 0.777). Significantly altered metabolite pathways associated with differential metabolites were glycine, serine and threonine metabolism, arginine and proline metabolism, and taurine and hypotaurine metabolism.Limitations: Due to the restriction of research centres, inconsistent urine collection times may have affected the quality of metabolic analyses. Moreover, it is necessary to compare metabolite levels that vary with ASD severity to better clarify the pathogenesis of ASD.Conclusions: Urinary amino acid metabolites significantly altered in children with ASD. Amino acid metabolic pathways might play important roles in the pathogenic mechanisms of ASD.Clinical Trial registration: National Study on Autism Spectrum Disorder in China (NCT02200679). Registered July 24, 2014. https://www.clinicaltrials.gov/ct2/show/NCT02200679

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“…They pointed out that many studies observed an increase in some Clostridium species, and a lower proportion of Bifidobacterium. Bezawada et al (2020) [19] also reported that the Sutterella genus was found to be more abundant in ASD children in many studies.…”

Section: Clinical Evidencementioning

confidence: 92%

Role of the Gut Microbiota in the Pathophysiology of Autism Spectrum Disorder: Clinical and Preclinical Evidence

et al. 2020

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Autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting 1 in 160 people in the world. Although there is a strong genetic heritability to ASD, it is now accepted that environmental factors can play a role in its onset. As the prevalence of gastrointestinal (GI) symptoms is four-times higher in ASD patients, the potential implication of the gut microbiota in this disorder is being increasingly studied. A disturbed microbiota composition has been demonstrated in ASD patients, accompanied by altered production of bacterial metabolites. Clinical studies as well as preclinical studies conducted in rodents have started to investigate the physiological functions that gut microbiota might disturb and thus underlie the pathophysiology of ASD. The first data support an involvement of the immune system and tryptophan metabolism, both in the gut and central nervous system. In addition, a few clinical studies and a larger number of preclinical studies found that modulation of the microbiota through antibiotic and probiotic treatments, or fecal microbiota transplantation, could improve behavior. Although the understanding of the role of the gut microbiota in the physiopathology of ASD is only in its early stages, the data gathered in this review highlight that this role should be taken in consideration.

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Autism Spectrum Disorder and the Gut Microbiota in Children: A Systematic Review

Cited by 70 publications

References 71 publications

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

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

Differential Metabolites in Chinese Autistic Children: A Multi-Centre Study Based on Urinary 1H-NMR Metabolomics Analysis

Role of the Gut Microbiota in the Pathophysiology of Autism Spectrum Disorder: Clinical and Preclinical Evidence

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