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). 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. 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.

Original languageEnglish (US)
Pages (from-to)121-131
Number of pages11
JournalAnaerobe
Volume49
DOIs
StatePublished - Feb 1 2018

Fingerprint

Microbiota
Feces
Haemophilus parainfluenzae
Prevotella
Thymine
2-Propanol
Autism Spectrum Disorder
Niacin
Discriminant Analysis
Glutamine
rRNA Genes
Aspartic Acid
gamma-Aminobutyric Acid
Cohort Studies
Magnetic Resonance Spectroscopy
Animal Models
Biomarkers
Sensitivity and Specificity

Keywords

  • Autism
  • Autism biomarkers
  • Fecal metabolites
  • Gut bacteria
  • Gut microbiome
  • Metabolomics

ASJC Scopus subject areas

  • Microbiology
  • Infectious Diseases

Cite this

Differences in fecal microbial metabolites and microbiota of children with autism spectrum disorders. / Kang, Dae Wook; Ilhan, Zehra Esra; Isern, Nancy G.; Hoyt, David W.; Howsmon, Daniel P.; Shaffer, Michael; Lozupone, Catherine A.; Hahn, Juergen; Adams, James; Krajmalnik-Brown, Rosa.

In: Anaerobe, Vol. 49, 01.02.2018, p. 121-131.

Research output: Contribution to journalArticle

Kang, Dae Wook ; Ilhan, Zehra Esra ; Isern, Nancy G. ; Hoyt, David W. ; Howsmon, Daniel P. ; Shaffer, Michael ; Lozupone, Catherine A. ; Hahn, Juergen ; Adams, James ; Krajmalnik-Brown, Rosa. / Differences in fecal microbial metabolites and microbiota of children with autism spectrum disorders. In: Anaerobe. 2018 ; Vol. 49. pp. 121-131.
@article{5e677218722c400a9bb86e46328316e7,
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). 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. 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.",
keywords = "Autism, Autism biomarkers, Fecal metabolites, Gut bacteria, Gut microbiome, Metabolomics",
author = "Kang, {Dae Wook} and Ilhan, {Zehra Esra} and Isern, {Nancy G.} and Hoyt, {David W.} and Howsmon, {Daniel P.} and Michael Shaffer and Lozupone, {Catherine A.} and Juergen Hahn and James Adams and Rosa Krajmalnik-Brown",
year = "2018",
month = "2",
day = "1",
doi = "10.1016/j.anaerobe.2017.12.007",
language = "English (US)",
volume = "49",
pages = "121--131",
journal = "Anaerobe",
issn = "1075-9964",
publisher = "Academic Press Inc.",

}

TY - JOUR

T1 - Differences in fecal microbial metabolites and microbiota of children with autism spectrum disorders

AU - Kang, Dae Wook

AU - Ilhan, Zehra Esra

AU - Isern, Nancy G.

AU - Hoyt, David W.

AU - Howsmon, Daniel P.

AU - Shaffer, Michael

AU - Lozupone, Catherine A.

AU - Hahn, Juergen

AU - Adams, James

AU - Krajmalnik-Brown, Rosa

PY - 2018/2/1

Y1 - 2018/2/1

N2 - 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. 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.

AB - 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. 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.

KW - Autism

KW - Autism biomarkers

KW - Fecal metabolites

KW - Gut bacteria

KW - Gut microbiome

KW - Metabolomics

UR - http://www.scopus.com/inward/record.url?scp=85040318286&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85040318286&partnerID=8YFLogxK

U2 - 10.1016/j.anaerobe.2017.12.007

DO - 10.1016/j.anaerobe.2017.12.007

M3 - Article

C2 - 29274915

AN - SCOPUS:85040318286

VL - 49

SP - 121

EP - 131

JO - Anaerobe

JF - Anaerobe

SN - 1075-9964

ER -