Plasma and Fecal Metabolite Profiles in Autism Spectrum Disorder

Brittany D. Needham, Mark D. Adame, Gloria Serena, Destanie R. Rose, Gregory M. Preston, Mary C. Conrad, A. Stewart Campbell, David H. Donabedian, Alessio Fasano, Paul Ashwood, Sarkis K. Mazmanian

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Background: 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. Methods: 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. Results: 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. Conclusions: These findings support a connection between metabolism, gastrointestinal physiology, and complex behavioral traits and may advance discovery and development of molecular biomarkers for ASD.

Original languageEnglish (US)
Pages (from-to)451-462
Number of pages12
JournalBiological Psychiatry
Volume89
Issue number5
DOIs
StatePublished - Mar 1 2021

Keywords

  • ASD
  • Autism spectrum disorder
  • Fecal metabolites
  • Metabolomics
  • Mitochondrial dysfunction
  • Phenolic metabolites
  • Plasma metabolites
  • Steroid hormones

ASJC Scopus subject areas

  • Biological Psychiatry

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