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Plasma and Fecal Metabolite Profiles in Autism Spectrum Disorder

Needham, Brittany D. and Adame, Mark D. and Serena, Gloria and Rose, Destanie R. and Preston, Gregory M. and Conrad, Mary C. and Campbell, A. Stewart and Donabedian, David H. and Fasano, Alessio and Ashwood, Paul and Mazmanian, Sarkis K. (2021) Plasma and Fecal Metabolite Profiles in Autism Spectrum Disorder. Biological Psychiatry, 89 (5). pp. 451-462. ISSN 0006-3223.

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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.

Item Type:Article
Related URLs:
URLURL TypeDescription Paper
Needham, Brittany D.0000-0002-0280-1886
Serena, Gloria0000-0003-1832-9974
Preston, Gregory M.0000-0001-6098-8223
Fasano, Alessio0000-0002-2134-0261
Ashwood, Paul0000-0002-4255-1893
Mazmanian, Sarkis K.0000-0003-2713-1513
Alternate Title:Plasma and Fecal Metabolite Profiles in ASD
Additional Information:© 2020 Society of Biological Psychiatry. This is an open access article under the CC BY-NC-ND license ( Received 15 April 2020, Revised 30 September 2020, Accepted 30 September 2020, Available online 10 October 2020. This work was supported by Autism Speaks (Grant No. 7567 [to PA, AF, and SKM]), the Johnson Foundation (to PA), the Brain Foundation (to PA), Genome, Environment, Microbiome, and Metabolome in Autism (Grant No. 825033 [to AF]), Axial Biotherapeutics (to SKM), and the National Institutes of Health (Grant No. HD090214 [to PA] and Grant No. MH100556 [to SKM]). We thank the MIND Institute study staff, and the dedication and commitment of the families who took part in these studies are gratefully acknowledged. ASC, DHD, and SKM have financial interest in Axial Biotherapeutics. AF has financial interest in Alba Therapeutics. GMP and MCC are employed by Axial Biotherapeutics. All other authors report no biomedical financial interests or potential conflicts of interest.
Funding AgencyGrant Number
Autism Speaks7567
Johnson FoundationUNSPECIFIED
Brain FoundationUNSPECIFIED
Genome, Environment, Microbiome, and Metabolome in Autism (GEMMA)825033
Axial BiotherapeuticsUNSPECIFIED
Subject Keywords:ASD; Autism spectrum disorder; Fecal metabolites; Metabolomics; Mitochondrial dysfunction; Phenolic metabolites; Plasma metabolites; Steroid hormones
Issue or Number:5
Record Number:CaltechAUTHORS:20200520-071052940
Persistent URL:
Official Citation: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, Plasma and Fecal Metabolite Profiles in Autism Spectrum Disorder, Biological Psychiatry, Volume 89, Issue 5, 2021, Pages 451-462, ISSN 0006-3223, (
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:103339
Deposited By: Tony Diaz
Deposited On:20 May 2020 15:39
Last Modified:03 Feb 2021 17:02

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