Dataset Information

Altered Gut Microbiota in Korean Children with Autism Spectrum Disorders.

ABSTRACT: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social and behavioral impairments. Recent studies have suggested that gut microbiota play a critical role in ASD pathogenesis. Herein, we investigated the fecal microflora of Korean ASD children to determine gut microbiota profiles associated with ASD. Specifically, fecal samples were obtained from 54 children with ASD and 38 age-matched children exhibiting typical development. Systematic bioinformatic analysis revealed that the composition of gut microbiota differed between ASD and typically developing children (TDC). Moreover, the total amounts of short-chain fatty acids, metabolites produced by bacteria, were increased in ASD children. At the phylum level, we found a significant decrease in the relative Bacteroidetes abundance of the ASD group, whereas Actinobacteria abundance was significantly increased. Furthermore, we found significantly lower Bacteroides levels and higher Bifidobacterium levels in the ASD group than in the TDC group at the genus level. Functional analysis of the microbiota in ASD children predicted that several pathways, including genetic information processing and amino acid metabolism, can be associated with ASD pathogenesis. Although more research is needed to determine whether the differences between ASD and TDC are actually related to ASD pathogenesis, these results provide further evidence of altered gut microbiota in children with ASD, possibly providing new perspectives on the diagnosis and therapeutic approaches for ASD patients.

SUBMITTER: Ha S

PROVIDER: S-EPMC8539113 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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Altered Gut Microbiota in Korean Children with Autism Spectrum Disorders.

Ha Sungji S Oh Donghun D Lee Sunghee S Park Jaewan J Ahn Jaeun J Choi Sungku S Cheon Keun-Ah KA

Nutrients 20210922 10

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social and behavioral impairments. Recent studies have suggested that gut microbiota play a critical role in ASD pathogenesis. Herein, we investigated the fecal microflora of Korean ASD children to determine gut microbiota profiles associated with ASD. Specifically, fecal samples were obtained from 54 children with ASD and 38 age-matched children exhibiting typical development. Systematic bioinformatic analysis reve ...[more]

PMID: 34684301

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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:Gastrointestinal symptoms are more prevalent in children with autism spectrum disorder (ASD) than in typically developing (TD) children. Constipation is a significant gastrointestinal comorbidity of ASD, but the associations among constipated autism spectrum disorder (C-ASD), microbiota and short-chain fatty acids (SCFAs) are still debated. We enrolled 80 children, divided into the C-ASD group (n = 40) and the TD group (n = 40). In this study, an integrated 16S rRNA gene sequencing and gas chromatography-mass spectrometry-based metabolomics approach was applied to explore the association of the gut microbiota and SCFAs in C-ASD children in China. The community diversity estimated by the Observe, Chao1, and ACE indices was significantly lower in the C-ASD group than in the TD group. We observed that Ruminococcaceae_UCG_002, Erysipelotrichaceae_UCG_003, Phascolarctobacterium, Megamonas, Ruminiclostridium_5, Parabacteroides, Prevotella_2, Fusobacterium, and Prevotella_9 were enriched in the C-ASD group, and Anaerostipes, Lactobacillus, Ruminococcus_gnavus_group, Lachnospiraceae_NK4A136_group, Ralstonia, Eubacterium_eligens_group, and Ruminococcus_1 were enriched in the TD group. The propionate levels, which were higher in the C-ASD group, were negatively correlated with the abundance of Lactobacillus taxa, but were positively correlated with the severity of ASD symptoms. The random forest model, based on the 16 representative discriminant genera, achieved a high accuracy (AUC = 0.924). In conclusion, we found that C-ASD is related to altered gut microbiota and SCFAs, especially decreased abundance of Lactobacillus and excessive propionate in faeces, which provide new clues to understand C-ASD and biomarkers for the diagnosis and potential strategies for treatment of the disorder. This study was registered in the Chinese Clinical Trial Registry ( www.chictr.org.cn ; trial registration number ChiCTR2100052106; date of registration: October 17, 2021).

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

Altered Gut Microbiota in Korean Children with Autism Spectrum Disorders.

Publications

Altered Gut Microbiota in Korean Children with Autism Spectrum Disorders.

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