1. Plasma and Fecal Metabolite Profiles in Autism Spectrum Disorder
- Author
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Needham, Brittany D, Adame, Mark D, Serena, Gloria, Rose, Destanie R, Preston, Gregory M, Conrad, Mary C, Campbell, A Stewart, Donabedian, David H, Fasano, Alessio, Ashwood, Paul, and Mazmanian, Sarkis K
- Subjects
Medical Biochemistry and Metabolomics ,Biomedical and Clinical Sciences ,Intellectual and Developmental Disabilities (IDD) ,Digestive Diseases ,Prevention ,Behavioral and Social Science ,Mental Health ,Pediatric ,Clinical Research ,Brain Disorders ,Autism ,Aetiology ,2.1 Biological and endogenous factors ,Mental health ,Animals ,Autism Spectrum Disorder ,Feces ,Gastrointestinal Microbiome ,Mice ,Pilot Projects ,Plasma ,ASD ,Autism spectrum disorder ,Fecal metabolites ,Metabolomics ,Mitochondrial dysfunction ,Phenolic metabolites ,Plasma metabolites ,Steroid hormones ,Biological Sciences ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Psychiatry ,Biological sciences ,Biomedical and clinical sciences ,Psychology - Abstract
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.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.
- Published
- 2021