Background Autism 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. Methods One 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. Results SRS 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). Conclusions ASD children with sleep disorder exhibited declines in the abundance of Faecalibacterium and Agathobacter , decreased leve...
Metabolic disturbance may be implicated in the pathogenesis of autism. This study aimed to investigate the gut metabolomic profiles of autistic children and to analyze potential interaction between gut metabolites with autistic symptoms and neurodevelopment levels. We involved 120 autistic and 60 neurotypical children. Autistic symptoms and neurodevelopment levels were assessed. Fecal samples were analyzed using untargeted liquid chromatography-tandem mass spectrometry methods. Our results showed the metabolic disturbances of autistic children involved in multiple vitamin and amino acid metabolism pathways, with the strongest enrichment identified for tryptophan metabolism, retinol metabolism, cysteine-methionine metabolism, and vitamin digestion and absorption. Differential gut metabolites were correlated to autistic symptoms and neurodevelopment levels. Our findings improved the understanding of the perturbations of metabolome networks in autism.
Background Accumulated evidence have supported metabolic disturbance may be associated with the pathogenesis of autism spectrum disorders (ASD). Despite abnormalities of some shared metabolic pathways, specific differential compounds are inconsistent in studies, which made a challenge to elucidate the role of metabolism in the mechanism of ASD. Besides, few researches have assessed the correlation between gut metabolites with symptoms of ASD. Objectives The present study aimed to evaluate the gut metabolomic profiles of children with ASD and to analyze potential interaction between gut metabolites with symptoms and neurodevelopment of ASD children. Methods In this cross-sectional case-control study, 120 aged 2–6 years ASD children and 60 sex and age matched typically developing (TD) children were included. Autistic symptoms were assessed with the Autism Behavior Checklist (ABC), Childhood Autism Rating Scale (CARS), and the Social Responsiveness Scale (SRS). Neurodevelopment was assessed with the Gesell Developmental Scale (GDS). Fecal samples were analyzed by untargeted liquid chromatography-mass spectrometry (LC-MS) methods, then systematic bioinformatic analyses were performed to characterize the gut metabolomic profiles of ASD and TD children. The correlations between metabolites and clinical assessment scores were assessed using Spearman correlation. Results ASD children exhibit gut metabolism perturbation compared with TD children. A total of 96 differential metabolites between the ASD and TD groups were identified, with 35 increased and 61 decreased in ASD group. The metabolic disturbance of ASD involved in multiple vitamins and amino acids metabolism pathways, with the strongest enrichment identified for tryptophan metabolism, retinol metabolism, cysteine and methionine metabolism, and vitamin digestion and absorption. The imbalanced gut metabolites are significantly correlated to symptoms and neurodevelopment of ASD children. Limitations This cross-sectional study revealed a correlation, but do not allow to prove causation of symptoms and gut metabolites outcome. The disease specificity of the metabolomic disturbance need to be evaluated in future studies.Conclusions ASD children have altered gut metabolite profiles compared with TD children, which mainly involved in multiple vitamins and amino acids metabolism pathways. Notably, vitamins metabolism abnormalities may play roles in the disturbance of amino acids metabolism. Imbalanced gut metabolites are related to symptoms and neurodevelopment of ASD children. Our findings provided an improved understanding of perturbations of metabolome networks in ASD.
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