Abstract

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.

Highlights

  • Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by early-appearing social communication deficits and restricted or repetitive behaviors1 3 Vol.:(0123456789)Journal of Autism and Developmental Disorders (Hyman et al, 2020)

  • We found that the differential metabolites between the ASD and typically developing (TD) groups were mainly involved in multiple vitamin and amino acid metabolism pathways

  • The supervised Partial least squares discriminant analysis (PLS-DA) showed that the ASD children with GI symptoms (ASD-GI, n = 58) and non-GI symptoms (ASD-nonGI, n = 62) were not partly clustered with specific metabolic profiles for each (ESI+ : ­R2Y = 0.27, ­Q2 = 0.10, p = 0.14; ESI-: ­R2Y = 0.25, ­Q2 = 0.06, p = 0.045),while the metabolic profiles of the both groups were different from the TD group

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Summary

Introduction

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by early-appearing social communication deficits and restricted or repetitive behaviors1 3 Vol.:(0123456789)Journal of Autism and Developmental Disorders (Hyman et al, 2020). ASD is often accompanied with other developmental or behavioral disorders, sleep problems, and gastrointestinal (GI) symptoms (Hyman et al, 2020). Metabolomics studies of urines, plasma, and fecal samples from ASD patients have shown disturbances of metabolism related to amino acids, oxidative stress, purine intermediates, and gut microbiota (Glinton & Elsea, 2019; Shen et al, 2020; Mohamadkhani, 2018; Kang et al, 2018). Previous studies are mainly focused on the metabolomic analysis of urines and blood, and analysis of gut microbiota composition, while studies of fecal metabolism are relatively rare in the context of ASD (Kang et al, 2018; Shen et al, 2020)

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