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...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2019-02-01
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| Series: | mSystems |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/mSystems.00321-18 |
| _version_ | 1819200425705865216 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-23T03:32:02Z |
| format | Article |
| id | doaj.art-e69c87d0e3c24ad5a3ff8d8400ff6e60 |
| institution | Directory Open Access Journal |
| issn | 2379-5077 |
| language | English |
| last_indexed | 2024-12-23T03:32:02Z |
| publishDate | 2019-02-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mSystems |
| spelling | doaj.art-e69c87d0e3c24ad5a3ff8d8400ff6e602022-12-21T18:01:39ZengAmerican Society for MicrobiologymSystems2379-50772019-02-014110.1128/mSystems.00321-18Alterations in Gut Glutamate Metabolism Associated with Changes in Gut Microbiota Composition in Children with Autism Spectrum DisorderMingbang Wang0Jing Wan1Han Rong2Fusheng He3Hui Wang4Jiaxiu Zhou5Chunquan Cai6Yan Wang7Ruihuan Xu8Zhaoqing Yin9Wenhao Zhou10Shanghai Key Laboratory of Birth Defects, Division of Neonatology, Children’s Hospital of Fudan University, National Center for Children’s Health, Shanghai, ChinaDivision of Neonatology, The People’s Hospital of Dehong Autonomous Prefecture, Mangshi, Yunnan, ChinaShenzhen Key Laboratory for Psychological Healthcare, Shenzhen Institute of Mental Health, Shenzhen Kangning Hospital, Shenzhen Mental Health Center, Shenzhen, ChinaImunobio, Shenzhen, Guangdong, ChinaXiamen branch of Children’s Hospital of Fudan University (Xiamen Children’s Hospital), Xiamen, Fujian, ChinaDivision of Psychology, Shenzhen Children’s Hospital, Shenzhen, Guangdong, ChinaDivision of Neurosurgery, Tianjin Children’s Hospital, Tianjin, ChinaImunobio, Shenzhen, Guangdong, ChinaClinical Laboratory, Longgang Central Hospital of Shenzhen, Guangdong, ChinaDivision of Neonatology, The People’s Hospital of Dehong Autonomous Prefecture, Mangshi, Yunnan, ChinaShanghai Key Laboratory of Birth Defects, Division of Neonatology, Children’s Hospital of Fudan University, National Center for Children’s Health, Shanghai, ChinaABSTRACT 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.https://journals.asm.org/doi/10.1128/mSystems.00321-18autismglutamategut microbiotaliquid chromatography-mass spectrometrymetabolomemetagenome |
| spellingShingle | 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 mSystems autism glutamate gut microbiota liquid chromatography-mass spectrometry metabolome metagenome |
| title | 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_short | 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 |
| topic | autism glutamate gut microbiota liquid chromatography-mass spectrometry metabolome metagenome |
| url | https://journals.asm.org/doi/10.1128/mSystems.00321-18 |
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