Alterations in Gut Glutamate Metabolism Associated with Changes in Gut Microbiota Composition in Children with Autism Spectrum Disorder

ABSTRACT Changes in the gut microenvironment may influence the pathogenesis of autism spectrum disorders (ASD). Here, we investigated the composition of the gut microbiota and metabolites in children with ASD. Ninety-two children with ASD and 42 age-matched children exhibiting typical development (T...

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Autores principales:	Mingbang Wang, Jing Wan, Han Rong, Fusheng He, Hui Wang, Jiaxiu Zhou, Chunquan Cai, Yan Wang, Ruihuan Xu, Zhaoqing Yin, Wenhao Zhou
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	autism glutamate gut microbiota liquid chromatography-mass spectrometry metabolome metagenome Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/e69c87d0e3c24ad5a3ff8d8400ff6e60
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spelling	oai:doaj.org-article:e69c87d0e3c24ad5a3ff8d8400ff6e602021-12-02T18:39:15ZAlterations in Gut Glutamate Metabolism Associated with Changes in Gut Microbiota Composition in Children with Autism Spectrum Disorder10.1128/mSystems.00321-182379-5077https://doaj.org/article/e69c87d0e3c24ad5a3ff8d8400ff6e602019-02-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSystems.00321-18https://doaj.org/toc/2379-5077ABSTRACT Changes in the gut microenvironment may influence the pathogenesis of autism spectrum disorders (ASD). Here, we investigated the composition of the gut microbiota and metabolites in children with ASD. Ninety-two children with ASD and 42 age-matched children exhibiting typical development (TD) were enrolled in the two-stage study. In the discovery stage, shotgun metagenomic sequencing and liquid chromatography-mass spectrometry (LC-MS) were performed simultaneously on fecal samples obtained from 43 children in the ASD group and 31 children in the TD group. Systematic bioinformatic analyses were performed to identify gut metabolites associated with altered gut microbiota composition. At the validation stage, differential metabolites were tested using LC-MS with an additional 49 and 11 children in the ASD and TD groups, respectively. Altered glutamate metabolites were found in the ASD group, along with a decline in 2-keto-glutaramic acid and an abundance of microbiota associated with glutamate metabolism. These changes in glutamate metabolism were correlated with lower levels of the highly abundant bacteria Bacteroides vulgatus and higher levels of the potentially harmful Eggerthella lenta and Clostridium botulinum. Lower gut cortisol levels have also been identified in the ASD group and associated with changes in gut microbiota glutamate metabolism. Finally, gut 2-keto-glutaramic acid was validated as a potential biomarker for ASD. The significant changes in the gut microenvironment in children with ASD may provide new insight into the cause of ASD and aid in the search for diagnostic and therapeutic approaches. IMPORTANCE Multiple lines of evidence suggest that the gut microbiota may play an important role in the pathogenesis of ASD, but the specific mechanism is still unclear. Through a comprehensive gut metagenomic and metabolome study of children with ASD, alterations in gut metabolite composition were found in children with ASD, and these alterations were linked to changes in gut microbiota composition. This may give us a deeper understanding of the role of gut microbiota in the pathogenesis of ASD.Mingbang WangJing WanHan RongFusheng HeHui WangJiaxiu ZhouChunquan CaiYan WangRuihuan XuZhaoqing YinWenhao ZhouAmerican Society for Microbiologyarticleautismglutamategut microbiotaliquid chromatography-mass spectrometrymetabolomemetagenomeMicrobiologyQR1-502ENmSystems, Vol 4, Iss 1 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	autism glutamate gut microbiota liquid chromatography-mass spectrometry metabolome metagenome Microbiology QR1-502
spellingShingle	autism glutamate gut microbiota liquid chromatography-mass spectrometry metabolome metagenome Microbiology QR1-502 Mingbang Wang Jing Wan Han Rong Fusheng He Hui Wang Jiaxiu Zhou Chunquan Cai Yan Wang Ruihuan Xu Zhaoqing Yin Wenhao Zhou Alterations in Gut Glutamate Metabolism Associated with Changes in Gut Microbiota Composition in Children with Autism Spectrum Disorder
description	ABSTRACT Changes in the gut microenvironment may influence the pathogenesis of autism spectrum disorders (ASD). Here, we investigated the composition of the gut microbiota and metabolites in children with ASD. Ninety-two children with ASD and 42 age-matched children exhibiting typical development (TD) were enrolled in the two-stage study. In the discovery stage, shotgun metagenomic sequencing and liquid chromatography-mass spectrometry (LC-MS) were performed simultaneously on fecal samples obtained from 43 children in the ASD group and 31 children in the TD group. Systematic bioinformatic analyses were performed to identify gut metabolites associated with altered gut microbiota composition. At the validation stage, differential metabolites were tested using LC-MS with an additional 49 and 11 children in the ASD and TD groups, respectively. Altered glutamate metabolites were found in the ASD group, along with a decline in 2-keto-glutaramic acid and an abundance of microbiota associated with glutamate metabolism. These changes in glutamate metabolism were correlated with lower levels of the highly abundant bacteria Bacteroides vulgatus and higher levels of the potentially harmful Eggerthella lenta and Clostridium botulinum. Lower gut cortisol levels have also been identified in the ASD group and associated with changes in gut microbiota glutamate metabolism. Finally, gut 2-keto-glutaramic acid was validated as a potential biomarker for ASD. The significant changes in the gut microenvironment in children with ASD may provide new insight into the cause of ASD and aid in the search for diagnostic and therapeutic approaches. IMPORTANCE Multiple lines of evidence suggest that the gut microbiota may play an important role in the pathogenesis of ASD, but the specific mechanism is still unclear. Through a comprehensive gut metagenomic and metabolome study of children with ASD, alterations in gut metabolite composition were found in children with ASD, and these alterations were linked to changes in gut microbiota composition. This may give us a deeper understanding of the role of gut microbiota in the pathogenesis of ASD.
format	article
author	Mingbang Wang Jing Wan Han Rong Fusheng He Hui Wang Jiaxiu Zhou Chunquan Cai Yan Wang Ruihuan Xu Zhaoqing Yin Wenhao Zhou
author_facet	Mingbang Wang Jing Wan Han Rong Fusheng He Hui Wang Jiaxiu Zhou Chunquan Cai Yan Wang Ruihuan Xu Zhaoqing Yin Wenhao Zhou
author_sort	Mingbang Wang
title	Alterations in Gut Glutamate Metabolism Associated with Changes in Gut Microbiota Composition in Children with Autism Spectrum Disorder
title_short	Alterations in Gut Glutamate Metabolism Associated with Changes in Gut Microbiota Composition in Children with Autism Spectrum Disorder
title_full	Alterations in Gut Glutamate Metabolism Associated with Changes in Gut Microbiota Composition in Children with Autism Spectrum Disorder
title_fullStr	Alterations in Gut Glutamate Metabolism Associated with Changes in Gut Microbiota Composition in Children with Autism Spectrum Disorder
title_full_unstemmed	Alterations in Gut Glutamate Metabolism Associated with Changes in Gut Microbiota Composition in Children with Autism Spectrum Disorder
title_sort	alterations in gut glutamate metabolism associated with changes in gut microbiota composition in children with autism spectrum disorder
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/e69c87d0e3c24ad5a3ff8d8400ff6e60
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Alterations in Gut Glutamate Metabolism Associated with Changes in Gut Microbiota Composition in Children with Autism Spectrum Disorder

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