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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 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 biomarker to separate ASD participants from the neurotypical group (78% sensitivity and 81%more » specificity). Consistent with our previous Arizona cohort study, we also confirmed lower gut microbial diversity and reduced relative abundances of 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. 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:
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Publication Date:
Research Org.:
Pacific Northwest National Laboratory (PNNL), Richland, WA (US), Environmental Molecular Sciences Laboratory (EMSL)
Sponsoring Org.:
USDOE
OSTI Identifier:
1422278
Report Number(s):
PNNL-SA-127135
Journal ID: ISSN 1075-9964; 49112; 48610; WN0219080
DOE Contract Number:  
AC05-76RL01830
Resource Type:
Journal Article
Resource Relation:
Journal Name: Anaerobe; Journal Volume: 49; Journal Issue: C
Country of Publication:
United States
Language:
English
Subject:
Environmental Molecular Sciences Laboratory

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., 2018. 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. 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., and Krajmalnik-Brown, Rosa. Thu . "Differences in fecal microbial metabolites and microbiota of children with autism spectrum disorders". United States. doi:10.1016/j.anaerobe.2017.12.007.
@article{osti_1422278,
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 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 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 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. 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 = {Thu Feb 01 00:00:00 EST 2018},
month = {Thu Feb 01 00:00:00 EST 2018}
}