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Title: Differences in fecal microbial metabolites and microbiota of children with autism spectrum disorders

Abstract

Evidence supporting that gut problems are linked to ASD symptoms has been accumulating both in humans and animal models of ASD. Gut microbes and their metabolites may be linked not only to GI problems but also to ASD behavior symptoms. Despite this high interest, most previous studies have looked mainly at microbial structure, and studies on fecal metabolites are rare in the context of ASD. Thus, we aimed to detect fecal metabolites that may be present at significantly different concentrations between 21 children with ASD and 23 neurotypical children and to investigate its possible link to human gut microbiome. Using 1H-NMR spectroscopy and 16S rRNA gene amplicon sequencing, we examined metabolite profiles and microbial compositions in fecal samples, respectively. Of the 59 metabolites detected, isopropanol concentrations were significantly higher in feces of children with ASD after multiple testing corrections. We also observed similar trends of fecal metabolites to previous studies; children with ASD have higher fecal p-cresol and possibly lower GABA concentrations. In addition, Fisher Discriminant Analysis (FDA) with leave-out-validation suggested that a group of metabolites-caprate, nicotinate, glutamine, thymine, and aspartate-may potentially function as a modest biomarker to separate ASD participants from the neurotypical group (78% sensitivity and 81% specificity).more » Consistent with our previous Arizona cohort study, we also confirmed lower gut microbial diversity and reduced relative abundances of phylotypes most closely related to Prevotella copri in children with ASD. After multiple testing corrections, we also learned that relative abundances of Feacalibacterium prausnitzii and Haemophilus parainfluenzae were lower in feces of children with ASD. In conclusion, despite a relatively short list of fecal metabolites, the data in this study support that children with ASD have altered metabolite profiles in feces when compared with neurotypical children and warrant further investigation of metabolites in larger cohorts.« less

Authors:
 [1];  [1];  [2]; ORCiD logo [2]; ORCiD logo [3];  [4];  [5];  [6]; ORCiD logo [7]; ORCiD logo [1]
+ Show Author Affiliations
  1. Arizona State Univ., Tempe, AZ (United States). Biodesign Swette Center for Environmental Biotechnology; Arizona State Univ., Tempe, AZ (United States). Biodesign Center for Fundamental and Applied Microbiomics
  2. Pacific Northwest National Lab. (PNNL), Richland, WA (United States). Environmental Molecular Sciences Lab. (EMSL)
  3. Rensselaer Polytechnic Inst., Troy, NY (United States). Dept. of Chemical and Biological Engineering; Rensselaer Polytechnic Inst., Troy, NY (United States). Center for Biotechnology and Interdisciplinary Studies
  4. Univ. of Colorado, Denver, CO (United States). Dept. of Medicine; Univ. of Colorado, Denver, CO (United States). Computational Bioscience Program
  5. Univ. of Colorado, Denver, CO (United States). Dept. of Medicine
  6. Rensselaer Polytechnic Inst., Troy, NY (United States). Dept. of Chemical and Biological Engineering; Rensselaer Polytechnic Inst., Troy, NY (United States). Center for Biotechnology and Interdisciplinary Studies; Rensselaer Polytechnic Inst., Troy, NY (United States). Dept. of Biomedical Engineering
  7. Arizona State Univ., Tempe, AZ (United States). School of Mechanical, Aerospace, Chemical, and Materials Engineering
Publication Date:
Research Org.:
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Biological and Environmental Research (BER)
OSTI Identifier:
1416969
Report Number(s):
PNNL-SA-127135
Journal ID: ISSN 1075-9964; PII: S1075996417302305
Grant/Contract Number:  
AC05-76RL01830
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
Anaerobe
Additional Journal Information:
Journal Volume: 49; Journal Issue: C; Journal ID: ISSN 1075-9964
Publisher:
Elsevier
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; Fecal metabolites; Metabolomics; Autism; Gut microbiome; Gut bacteria; Autism biomarkers

Citation Formats

Kang, Dae-Wook, Ilhan, Zehra Esra, Isern, Nancy G., Hoyt, David W., Howsmon, Daniel P., Shaffer, Michael, Lozupone, Catherine A., Hahn, Juergen, Adams, James B., and Krajmalnik-Brown, Rosa. Differences in fecal microbial metabolites and microbiota of children with autism spectrum disorders. United States: N. p., 2017. Web. doi:10.1016/J.ANAEROBE.2017.12.007.
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Kang, Dae-Wook, Ilhan, Zehra Esra, Isern, Nancy G., Hoyt, David W., Howsmon, Daniel P., Shaffer, Michael, Lozupone, Catherine A., Hahn, Juergen, Adams, James B., & Krajmalnik-Brown, Rosa. Differences in fecal microbial metabolites and microbiota of children with autism spectrum disorders. United States. doi:10.1016/J.ANAEROBE.2017.12.007.
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Kang, Dae-Wook, Ilhan, Zehra Esra, Isern, Nancy G., Hoyt, David W., Howsmon, Daniel P., Shaffer, Michael, Lozupone, Catherine A., Hahn, Juergen, Adams, James B., and Krajmalnik-Brown, Rosa. Fri . "Differences in fecal microbial metabolites and microbiota of children with autism spectrum disorders". United States. doi:10.1016/J.ANAEROBE.2017.12.007. https://www.osti.gov/servlets/purl/1416969.
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@article{osti_1416969,
title = {Differences in fecal microbial metabolites and microbiota of children with autism spectrum disorders},
author = {Kang, Dae-Wook and Ilhan, Zehra Esra and Isern, Nancy G. and Hoyt, David W. and Howsmon, Daniel P. and Shaffer, Michael and Lozupone, Catherine A. and Hahn, Juergen and Adams, James B. and Krajmalnik-Brown, Rosa},
abstractNote = {Evidence supporting that gut problems are linked to ASD symptoms has been accumulating both in humans and animal models of ASD. Gut microbes and their metabolites may be linked not only to GI problems but also to ASD behavior symptoms. Despite this high interest, most previous studies have looked mainly at microbial structure, and studies on fecal metabolites are rare in the context of ASD. Thus, we aimed to detect fecal metabolites that may be present at significantly different concentrations between 21 children with ASD and 23 neurotypical children and to investigate its possible link to human gut microbiome. Using 1H-NMR spectroscopy and 16S rRNA gene amplicon sequencing, we examined metabolite profiles and microbial compositions in fecal samples, respectively. Of the 59 metabolites detected, isopropanol concentrations were significantly higher in feces of children with ASD after multiple testing corrections. We also observed similar trends of fecal metabolites to previous studies; children with ASD have higher fecal p-cresol and possibly lower GABA concentrations. In addition, Fisher Discriminant Analysis (FDA) with leave-out-validation suggested that a group of metabolites-caprate, nicotinate, glutamine, thymine, and aspartate-may potentially function as a modest biomarker to separate ASD participants from the neurotypical group (78% sensitivity and 81% specificity). Consistent with our previous Arizona cohort study, we also confirmed lower gut microbial diversity and reduced relative abundances of phylotypes most closely related to Prevotella copri in children with ASD. After multiple testing corrections, we also learned that relative abundances of Feacalibacterium prausnitzii and Haemophilus parainfluenzae were lower in feces of children with ASD. In conclusion, despite a relatively short list of fecal metabolites, the data in this study support that children with ASD have altered metabolite profiles in feces when compared with neurotypical children and warrant further investigation of metabolites in larger cohorts.},
doi = {10.1016/J.ANAEROBE.2017.12.007},
journal = {Anaerobe},
issn = {1075-9964},
number = C,
volume = 49,
place = {United States},
year = {2017},
month = {12}
}
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Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record
DOI:  10.1016/J.ANAEROBE.2017.12.007
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Cited by: 13 works
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Table 1 Table 1: Summary of subject characteristics.
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Works referencing / citing this record:

The phenolic interactome and gut microbiota: opportunities and challenges in developing applications for schizophrenia and autism
journal, May 2019

  • Jaskiw, George E.; Obrenovich, Mark E.; Donskey, Curtis J.
  • Psychopharmacology, Vol. 236, Issue 5
  • DOI: 10.1007/s00213-019-05267-3

Annual Research Review: Critical windows – the microbiota–gut–brain axis in neurocognitive development
journal, November 2019

  • Cowan, Caitlin S. M.; Dinan, Timothy G.; Cryan, John F.
  • Journal of Child Psychology and Psychiatry
  • DOI: 10.1111/jcpp.13156

The Microbiota-Gut-Brain Axis
journal, October 2019

  • Cryan, John F.; O'Riordan, Kenneth J.; Cowan, Caitlin S. M.
  • Physiological Reviews, Vol. 99, Issue 4
  • DOI: 10.1152/physrev.00018.2018

The phenolic interactome and gut microbiota: opportunities and challenges in developing applications for schizophrenia and autism
journal, May 2019

  • Jaskiw, George E.; Obrenovich, Mark E.; Donskey, Curtis J.
  • Psychopharmacology, Vol. 236, Issue 5
  • DOI: 10.1007/s00213-019-05267-3

Annual Research Review: Critical windows – the microbiota–gut–brain axis in neurocognitive development
journal, November 2019

  • Cowan, Caitlin S. M.; Dinan, Timothy G.; Cryan, John F.
  • Journal of Child Psychology and Psychiatry
  • DOI: 10.1111/jcpp.13156

The Microbiota-Gut-Brain Axis
journal, October 2019

  • Cryan, John F.; O'Riordan, Kenneth J.; Cowan, Caitlin S. M.
  • Physiological Reviews, Vol. 99, Issue 4
  • DOI: 10.1152/physrev.00018.2018
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    Table 1 (p. 35)table
    Table 2 (p. 36)table
    Table 3 (p. 37)table
    Table 4 (p. 38)table
    Table 5 (p. 39)table
    Figure 1 (p. 40)figure
    Figure 2 (p. 41)figure
    Figure 3 (p. 42)figure
    Figure 4 (p. 43)figure
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