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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. (2020) Plasma and Fecal Metabolite Profiles in Autism Spectrum Disorder. Biological Psychiatry . ISSN 0006-3223. (In Press) https://resolver.caltech.edu/CaltechAUTHORS:20200520-071052940

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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 (GI) dysfunction, and altered gut microbiome compositions. Methods: We sought to better understand non-behavioral features of ASD by determining molecular signatures in peripheral tissues through mass spectrometry methods (LC/MS and DMS-MS) with broad panels of identified metabolites. Herein, we present the global metabolome of 231 plasma and 97 fecal samples from a large cohort of children with ASD and typically developing (TD) controls. Results: Differences in amino acid, lipid, and xenobiotic metabolism discriminate ASD and TD samples. Our results implicate oxidative stress and mitochondrial dysfunction, hormone level elevations, lipid profile changes, and altered levels of phenolic microbial metabolites. We also reveal correlations between specific metabolite profiles and clinical behavior scores. Furthermore, a summary of metabolites modestly associated with GI dysfunction in ASD are provided, and a pilot study of metabolites that can be transferred via fecal microbial transplant into mice were identified. Conclusions: These findings support a connection between metabolism, GI physiology, and complex behavioral traits, and may advance discovery and development of molecular biomarkers for ASD.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1016/j.biopsych.2020.09.025DOIArticle
https://doi.org/10.1101/2020.05.17.098806DOIDiscussion Paper
ORCID:
AuthorORCID
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 Published by Elsevier Inc on behalf of Society of Biological Psychiatry. Under an Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0). Received 15 April 2020, Revised 30 September 2020, Accepted 30 September 2020, Available online 10 October 2020. This work was supported by grants from Autism Speaks (Grant #7567 to P.A., A.F. and S.K.M.); the Johnson Foundation (to P.A.); the Brain Foundation (to P.A.); Genome, Environment, Microbiome, and Metabolome in Autism (GEMMA) (#825033 to AF); Axial Biotherapeutics (to S.K.M.); and the National Institutes of Health (HD090214 to P.A.) and (MH100556 to S.K.M.). We would like to thank the MIND Institute study staff, and the dedication and commitment of the families who took part in these studies is gratefully acknowledged. Declaration of Interests: A.S.C., D.H.D. and S.K.M. have financial interest in Axial Biotherapeutics. A.F. has financial interest in Alba Therapeutics. G.M.P. and M.C.C. are employed by Axial Biotherapeutics. All other authors report no biomedical financial interests or potential conflicts of interest.
Funders:
Funding AgencyGrant Number
Autism Speaks7567
Johnson FoundationUNSPECIFIED
Brain FoundationUNSPECIFIED
Genome, Environment, Microbiome, and Metabolome in Autism (GEMMA)825033
Axial BiotherapeuticsUNSPECIFIED
NIHHD090214
NIHMH100556
Subject Keywords:Autism Spectrum Disorder, ASD, metabolomics, plasma metabolites, fecal metabolites, steroid hormones, mitochondrial dysfunction, phenolic metabolites
Record Number:CaltechAUTHORS:20200520-071052940
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20200520-071052940
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, 2020, ISSN 0006-3223, https://doi.org/10.1016/j.biopsych.2020.09.025. (http://www.sciencedirect.com/science/article/pii/S0006322320319855)
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:103339
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:20 May 2020 15:39
Last Modified:25 Nov 2020 18:44

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