Altered gut microbial profile is associated with abnormal metabolism activity of Autism Spectrum Disorder

Abstract

Autism Spectrum Disorder (ASD) is a severe neurodevelopmental disorder. To enhance the understanding of the gut microbiota structure in ASD children at different ages as well as the relationship between gut microbiota and fecal metabolites, we first used the 16S rRNA sequencing to evaluate the gut microbial population in a cohort of 143 children aged 2-13 years old. We found that the α-diversity of ASD group showed no significant change with age, while the TD group showed increased α-diversity with age, which indicates that the compositional development of the gut microbiota in ASD varies at different ages in ways that are not consistent with TD group. Recent studies have shown that chronic constipation is one of the most commonly obvious gastrointestinal (GI) symptoms along with ASD core symptoms. To further investigate the potential interaction effects between ASD and GI symptoms, the 30 C-ASD and their aged-matched TD were picked out to perform metagenomics analysis. We observed that C-ASD group displayed decreased diversity, depletion of species of Sutterella, Prevotella, and Bacteroides as well as dysregulation of associated metabolism activities, which may involve in the pathogenesis of C-ASD. Consistent with metagenomic analysis, liquid chromatography-mass spectrometry (LC/ MS) revealed some of the differential metabolites between C-ASD and TD group were involved in the metabolic network of neurotransmitters including serotonin, dopamine, histidine, and GABA. Furthermore, we found these differences in metabolites were associated with altered abundance of specific bacteria. The study suggested possible future modalities for ASD intervention through targeting the specific bacteria associated with neurotransmitter metabolism.

A quasi-paired cohort strategy reveals the impaired detoxifying function of microbes in the gut of autistic children

“…Compared to targeted sequencing of 16 S ribosomal DNA (rDNA), which only presents species profiles, shotgun sequencing is more informative, as it provides comprehensive information for the inference of concrete metabolic pathways and physiological functions of the microbiome ( 11 ). Although few studies of shotgun-based metagenome analysis have been reported for the ASD intestinal microbiome ( 12 , 13 ), obstacles remain because of high interindividual diversity, which is influenced by a wide range of factors such as genetics, age, diet, and healthy conditions ( 14 ). The individual diversity is often so great and difficult to control that it even overwhelms disease-associated alterations and profoundly affects the identification of disease-associated microbiome features.…”

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

“…MD Angelis et al [12] found higher amounts of tryptophan and 3methylindole in the feces of children with ASD. Dan Z et al [38] also reported abnormal metabolism of tryptophan in the gut of ASD children. An experiment in mice model of autism found a decrease of serotonin in intestine mucosal [39].…”

Alterations of gut microbiota composition in neonates conceived by assisted reproductive technology and its relation to infant growth

“…The differences between any two network structures were compared by node closeness centralities and shared correlations. 42 The shared correlations between two groups were defined the edges with the same nodes in two co-occurrence networks. Closeness centralities of the nodes was calculated by Cytoscape (v3.6.1) to measure node centralities in each network.…”