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 »
- Authors:
-
[2];
[3];
[7];
[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
- Pacific Northwest National Lab. (PNNL), Richland, WA (United States). Environmental Molecular Sciences Lab. (EMSL)
- 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
- Univ. of Colorado, Denver, CO (United States). Dept. of Medicine; Univ. of Colorado, Denver, CO (United States). Computational Bioscience Program
- Univ. of Colorado, Denver, CO (United States). Dept. of Medicine
- 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
- Arizona State Univ., Tempe, AZ (United States). School of Mechanical, Aerospace, Chemical, and Materials Engineering
- Publication Date:
- Research Org.:
- Pacific Northwest National Laboratory (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:
- 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.
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. https://doi.org/10.1016/J.ANAEROBE.2017.12.007
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. https://doi.org/10.1016/J.ANAEROBE.2017.12.007. https://www.osti.gov/servlets/purl/1416969.
@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},
number = C,
volume = 49,
place = {United States},
year = {Fri Dec 22 00:00:00 EST 2017},
month = {Fri Dec 22 00:00:00 EST 2017}
}
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