Alterations in Gut Vitamins and Amino Acids Metabolism are Associated with Symptoms and Neurodevelopment of Children with Autism Spectrum Disorders

Abstract

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.