Plasma and Fecal Metabolite Profiles in Autism Spectrum Disorder
Autism spectrum disorder (ASD) is a neurodevelopmental condition with hallmark behavioral manifestations including impaired social communication and restricted repetitive behavior. In addition, many affected individuals display metabolic imbalances, immune dysregulation, gastrointestinal dysfunction...
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| Published in | Biological psychiatry (1969) Vol. 89; no. 5; pp. 451 - 462 |
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| Main Authors | , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Elsevier Inc
01.03.2021
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| Abstract | Autism spectrum disorder (ASD) is a neurodevelopmental condition with hallmark behavioral manifestations including impaired social communication and restricted repetitive behavior. In addition, many affected individuals display metabolic imbalances, immune dysregulation, gastrointestinal dysfunction, and altered gut microbiome compositions.
We sought to better understand nonbehavioral features of ASD by determining molecular signatures in peripheral tissues through mass spectrometry methods (ultrahigh performance liquid chromatography–tandem mass spectrometry) with broad panels of identified metabolites. Herein, we compared the global metabolome of 231 plasma and 97 fecal samples from a large cohort of children with ASD and typically developing control children.
Differences in amino acid, lipid, and xenobiotic metabolism distinguished ASD and typically developing samples. Our results implicated oxidative stress and mitochondrial dysfunction, hormone level elevations, lipid profile changes, and altered levels of phenolic microbial metabolites. We also revealed correlations between specific metabolite profiles and clinical behavior scores. Furthermore, a summary of metabolites modestly associated with gastrointestinal dysfunction in ASD is provided, and a pilot study of metabolites that can be transferred via fecal microbial transplant into mice is identified.
These findings support a connection between metabolism, gastrointestinal physiology, and complex behavioral traits and may advance discovery and development of molecular biomarkers for ASD. |
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| AbstractList | Autism spectrum disorder (ASD) is a neurodevelopmental condition with hallmark behavioral manifestations including impaired social communication and restricted repetitive behavior. In addition, many affected individuals display metabolic imbalances, immune dysregulation, gastrointestinal dysfunction, and altered gut microbiome compositions.
We sought to better understand nonbehavioral features of ASD by determining molecular signatures in peripheral tissues through mass spectrometry methods (ultrahigh performance liquid chromatography–tandem mass spectrometry) with broad panels of identified metabolites. Herein, we compared the global metabolome of 231 plasma and 97 fecal samples from a large cohort of children with ASD and typically developing control children.
Differences in amino acid, lipid, and xenobiotic metabolism distinguished ASD and typically developing samples. Our results implicated oxidative stress and mitochondrial dysfunction, hormone level elevations, lipid profile changes, and altered levels of phenolic microbial metabolites. We also revealed correlations between specific metabolite profiles and clinical behavior scores. Furthermore, a summary of metabolites modestly associated with gastrointestinal dysfunction in ASD is provided, and a pilot study of metabolites that can be transferred via fecal microbial transplant into mice is identified.
These findings support a connection between metabolism, gastrointestinal physiology, and complex behavioral traits and may advance discovery and development of molecular biomarkers for ASD. Autism spectrum disorder (ASD) is a neurodevelopmental condition with hallmark behavioral manifestations including impaired social communication and restricted repetitive behavior. In addition, many affected individuals display metabolic imbalances, immune dysregulation, gastrointestinal dysfunction, and altered gut microbiome compositions.BACKGROUNDAutism spectrum disorder (ASD) is a neurodevelopmental condition with hallmark behavioral manifestations including impaired social communication and restricted repetitive behavior. In addition, many affected individuals display metabolic imbalances, immune dysregulation, gastrointestinal dysfunction, and altered gut microbiome compositions.We sought to better understand nonbehavioral features of ASD by determining molecular signatures in peripheral tissues through mass spectrometry methods (ultrahigh performance liquid chromatography-tandem mass spectrometry) with broad panels of identified metabolites. Herein, we compared the global metabolome of 231 plasma and 97 fecal samples from a large cohort of children with ASD and typically developing control children.METHODSWe sought to better understand nonbehavioral features of ASD by determining molecular signatures in peripheral tissues through mass spectrometry methods (ultrahigh performance liquid chromatography-tandem mass spectrometry) with broad panels of identified metabolites. Herein, we compared the global metabolome of 231 plasma and 97 fecal samples from a large cohort of children with ASD and typically developing control children.Differences in amino acid, lipid, and xenobiotic metabolism distinguished ASD and typically developing samples. Our results implicated oxidative stress and mitochondrial dysfunction, hormone level elevations, lipid profile changes, and altered levels of phenolic microbial metabolites. We also revealed correlations between specific metabolite profiles and clinical behavior scores. Furthermore, a summary of metabolites modestly associated with gastrointestinal dysfunction in ASD is provided, and a pilot study of metabolites that can be transferred via fecal microbial transplant into mice is identified.RESULTSDifferences in amino acid, lipid, and xenobiotic metabolism distinguished ASD and typically developing samples. Our results implicated oxidative stress and mitochondrial dysfunction, hormone level elevations, lipid profile changes, and altered levels of phenolic microbial metabolites. We also revealed correlations between specific metabolite profiles and clinical behavior scores. Furthermore, a summary of metabolites modestly associated with gastrointestinal dysfunction in ASD is provided, and a pilot study of metabolites that can be transferred via fecal microbial transplant into mice is identified.These findings support a connection between metabolism, gastrointestinal physiology, and complex behavioral traits and may advance discovery and development of molecular biomarkers for ASD.CONCLUSIONSThese findings support a connection between metabolism, gastrointestinal physiology, and complex behavioral traits and may advance discovery and development of molecular biomarkers for ASD. AbstractBackgroundAutism spectrum disorder (ASD) is a neurodevelopmental condition with hallmark behavioral manifestations including impaired social communication and restricted repetitive behavior. In addition, many affected individuals display metabolic imbalances, immune dysregulation, gastrointestinal dysfunction, and altered gut microbiome compositions. MethodsWe sought to better understand nonbehavioral features of ASD by determining molecular signatures in peripheral tissues through mass spectrometry methods (ultrahigh performance liquid chromatography–tandem mass spectrometry) with broad panels of identified metabolites. Herein, we compared the global metabolome of 231 plasma and 97 fecal samples from a large cohort of children with ASD and typically developing control children. ResultsDifferences in amino acid, lipid, and xenobiotic metabolism distinguished ASD and typically developing samples. Our results implicated oxidative stress and mitochondrial dysfunction, hormone level elevations, lipid profile changes, and altered levels of phenolic microbial metabolites. We also revealed correlations between specific metabolite profiles and clinical behavior scores. Furthermore, a summary of metabolites modestly associated with gastrointestinal dysfunction in ASD is provided, and a pilot study of metabolites that can be transferred via fecal microbial transplant into mice is identified. ConclusionsThese findings support a connection between metabolism, gastrointestinal physiology, and complex behavioral traits and may advance discovery and development of molecular biomarkers for ASD. |
| Author | Mazmanian, Sarkis K. Needham, Brittany D. Rose, Destanie R. Preston, Gregory M. Ashwood, Paul Donabedian, David H. Campbell, A. Stewart Serena, Gloria Adame, Mark D. Conrad, Mary C. Fasano, Alessio |
| AuthorAffiliation | 2 Division of Pediatric Gastroenterology and Nutrition, Mucosal Immunology and Biology Research Center, Massachusetts General Hospital for Children, Boston, MA, 02114, USA 3 Department of Medical Microbiology and Immunology, University of California Davis, Davis, CA, 95616, USA 1 Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, 91125, USA 5 Axial Biotherapeutics, Waltham, MA, 02451, USA 4 The M.I.N.D. Institute, University of California, Davis, Sacramento, CA, 95817, USA |
| AuthorAffiliation_xml | – name: 2 Division of Pediatric Gastroenterology and Nutrition, Mucosal Immunology and Biology Research Center, Massachusetts General Hospital for Children, Boston, MA, 02114, USA – name: 5 Axial Biotherapeutics, Waltham, MA, 02451, USA – name: 3 Department of Medical Microbiology and Immunology, University of California Davis, Davis, CA, 95616, USA – name: 4 The M.I.N.D. Institute, University of California, Davis, Sacramento, CA, 95817, USA – name: 1 Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, 91125, USA |
| Author_xml | – sequence: 1 givenname: Brittany D. orcidid: 0000-0002-0280-1886 surname: Needham fullname: Needham, Brittany D. email: bneedham@caltech.edu organization: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California – sequence: 2 givenname: Mark D. surname: Adame fullname: Adame, Mark D. organization: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California – sequence: 3 givenname: Gloria orcidid: 0000-0003-1832-9974 surname: Serena fullname: Serena, Gloria organization: Division of Pediatric Gastroenterology and Nutrition, Mucosal Immunology and Biology Research Center, Massachusetts General Hospital for Children, Boston, Massachusetts – sequence: 4 givenname: Destanie R. surname: Rose fullname: Rose, Destanie R. organization: Department of Medical Microbiology and Immunology, University of California, Davis, Davis, California – sequence: 5 givenname: Gregory M. surname: Preston fullname: Preston, Gregory M. organization: Axial Biotherapeutics, Waltham, Massachusetts – sequence: 6 givenname: Mary C. surname: Conrad fullname: Conrad, Mary C. organization: Axial Biotherapeutics, Waltham, Massachusetts – sequence: 7 givenname: A. Stewart surname: Campbell fullname: Campbell, A. Stewart organization: Axial Biotherapeutics, Waltham, Massachusetts – sequence: 8 givenname: David H. surname: Donabedian fullname: Donabedian, David H. organization: Axial Biotherapeutics, Waltham, Massachusetts – sequence: 9 givenname: Alessio orcidid: 0000-0002-2134-0261 surname: Fasano fullname: Fasano, Alessio organization: Division of Pediatric Gastroenterology and Nutrition, Mucosal Immunology and Biology Research Center, Massachusetts General Hospital for Children, Boston, Massachusetts – sequence: 10 givenname: Paul surname: Ashwood fullname: Ashwood, Paul organization: Department of Medical Microbiology and Immunology, University of California, Davis, Davis, California – sequence: 11 givenname: Sarkis K. surname: Mazmanian fullname: Mazmanian, Sarkis K. email: sarkis@caltech.edu organization: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/33342544$$D View this record in MEDLINE/PubMed |
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| Keywords | Metabolomics ASD Mitochondrial dysfunction Phenolic metabolites Plasma metabolites Autism spectrum disorder Fecal metabolites Steroid hormones |
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| PublicationTitleAlternate | Biol Psychiatry |
| PublicationYear | 2021 |
| Publisher | Elsevier Inc |
| Publisher_xml | – name: Elsevier Inc |
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| Snippet | Autism spectrum disorder (ASD) is a neurodevelopmental condition with hallmark behavioral manifestations including impaired social communication and restricted... AbstractBackgroundAutism spectrum disorder (ASD) is a neurodevelopmental condition with hallmark behavioral manifestations including impaired social... |
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| SubjectTerms | Animals ASD Autism Spectrum Disorder Fecal metabolites Feces Gastrointestinal Microbiome Metabolomics Mice Mitochondrial dysfunction Phenolic metabolites Pilot Projects Plasma Plasma metabolites Psychiatric/Mental Health Steroid hormones |
| Title | Plasma and Fecal Metabolite Profiles in Autism Spectrum Disorder |
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