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. 2020 Sep 2;11(5):1246-1267.
doi: 10.1080/19490976.2020.1747329. Epub 2020 Apr 21.

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

Zhou Dan  1   2   3   4 , Xuhua Mao  5 , Qisha Liu  1   2   3 , Mengchen Guo  1   2   3 , Yaoyao Zhuang  1   2   3 , Zhi Liu  1   2   3 , Kun Chen  1   2   3 , Junyu Chen  1   2   3 , Rui Xu  1   2   3 , Junming Tang  5 , Lianhong Qin  6 , Bing Gu  7 , Kangjian Liu  4 , Chuan Su  1 , Faming Zhang  4 , Yankai Xia  8 , Zhibin Hu  8 , Xingyin Liu  1   2   3   4
Affiliations

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

Zhou Dan et al. Gut Microbes. .

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.

Keywords: 16s rRNA; ASD; gut microbiota; metabolism; metagenomics; neurotransmitter.

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Figures

Figure 1.
Figure 1.
The shift of gut microbiota in typically developing (TD) and ASD children according to the 16S rRNA data.
Figure 2.
Figure 2.
Genera are strikingly different across TD and ASD children.
Figure 3.
Figure 3.
The gut microbiota divergence in ASD with constipation (C-ASD) and TD children based on the metagenomic sequencing data.
Figure 4.
Figure 4.
Microbial gene functions annotation on KEGG in ASD with constipation (C-ASD) and TD children.
Figure 5.
Figure 5.
Aberrant metabolic patterns in ASD with constipation (C-ASD) and typically developing (TD) children.
Figure 6.
Figure 6.
KEGG pathway of the differential metabolites between C-ASD and TD group (Fold change >1.25, VIP ≥ 1, P < .05 T test).
Figure 7.
Figure 7.
The summary of gut microbiota composition and metabolism analysis between ASD and TD.
See this image and copyright information in PMC

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