机构：[1]Shanghai Key Laboratory of Birth Defects, Division of Neonatology, Children’s Hospital of Fudan University, National Center for Children’s Health, Shanghai, China[2]Division of Neonatology, The People’s Hospital of Dehong Autonomous Prefecture, Mangshi, Yunnan, China[3]Shenzhen Key Laboratory for Psychological Healthcare, Shenzhen Institute of Mental Health, Shenzhen Kangning Hospital, Shenzhen Mental Health Center, Shenzhen, China[4]Imunobio, Shenzhen, Guangdong, China[5]Xiamen branch of Children’s Hospital of Fudan University (Xiamen Children’s Hospital), Xiamen, Fujian, China[6]Division of Psychology, Shenzhen Children’s Hospital, Shenzhen, Guangdong, China[7]Division of Neurosurgery, Tianjin Children’s Hospital, Tianjin, China[8]Clinical Laboratory, Longgang Central Hospital of Shenzhen, Guangdong, China
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.
基金：
National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81701351, 81720108018]; Shenzhen Science Technology and Innovation Commission [JCYJ20170413093358429, JCYJ20160427101538845]; Shanghai Municipal Commission of Health and Family Planning [GDEK201701]; Shanghai Shen Kang Hospital Development Center [SHDC12017110]; Sanming Project of Medicine in Shenzhen [SZSM201812052]; Longgang Science Technology and Innovation Commission of Shenzhen [LGKCYLWS2018000107]; National Key Research and Development Program of China [2016YFC0905100, 2017YFA0104204]; Key Project of Tianjin Health Care Professionals [16KG166]
第一作者机构：[1]Shanghai Key Laboratory of Birth Defects, Division of Neonatology, Children’s Hospital of Fudan University, National Center for Children’s Health, Shanghai, China
共同第一作者：
通讯作者：
通讯机构：[1]Shanghai Key Laboratory of Birth Defects, Division of Neonatology, Children’s Hospital of Fudan University, National Center for Children’s Health, Shanghai, China[2]Division of Neonatology, The People’s Hospital of Dehong Autonomous Prefecture, Mangshi, Yunnan, China
推荐引用方式(GB/T 7714)：
Wang Mingbang,Wan Jing,Rong Han,et al.Alterations in Gut Glutamate Metabolism Associated with Changes in Gut Microbiota Composition in Children with Autism Spectrum Disorder[J].MSYSTEMS.2019,4(1):-.doi:10.1128/mSystems.00321-18.
APA：
Wang, Mingbang,Wan, Jing,Rong, Han,He, Fusheng,Wang, Hui...&Zhou, Wenhao.(2019).Alterations in Gut Glutamate Metabolism Associated with Changes in Gut Microbiota Composition in Children with Autism Spectrum Disorder.MSYSTEMS,4,(1)
MLA：
Wang, Mingbang,et al."Alterations in Gut Glutamate Metabolism Associated with Changes in Gut Microbiota Composition in Children with Autism Spectrum Disorder".MSYSTEMS 4..1(2019):-
生物学