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 B.; Krajmalnik-Brown, Rosa

doi:10.1016/J.ANAEROBE.2017.12.007

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

Journal Article · 22 December 2017 · Anaerobe

DOI: https://doi.org/10.1016/J.ANAEROBE.2017.12.007 · OSTI ID:1416969

Kang, Dae-Wook ^[1]; Ilhan, Zehra Esra ^[1]; Isern, Nancy G. ^[2];

^[2];

^[3]; Shaffer, Michael ^[4]; Lozupone, Catherine A. ^[5]; Hahn, Juergen ^[6];

^[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

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.

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Research Organization:: Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER)

Grant/Contract Number:: AC05-76RL01830

OSTI ID:: 1416969

Report Number(s):: PNNL-SA-127135; PII: S1075996417302305

Journal Information:: Anaerobe, Vol. 49, Issue C; ISSN 1075-9964

Publisher:: ElsevierCopyright Statement

Country of Publication:: United States

Language:: English

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Probiotic supplementation in trained trotter horses: effect on blood clinical pathology data and urine metabolomic assessed in field Laghi, Luca; Zhu, Chenglin; Campagna, Giuseppe Journal of Applied Physiology, Vol. 125, Issue 2 https://doi.org/10.1152/japplphysiol.01131.2017	journal	August 2018
An approach to gut microbiota profile in children with autism spectrum disorder Andreo‐Martínez, Pedro; García‐Martínez, Nuria; Sánchez‐Samper, Elvira Pilar Environmental Microbiology Reports, Vol. 12, Issue 2 https://doi.org/10.1111/1758-2229.12810	journal	November 2019
Tobacco use and cessation in psychiatric disorders: National Institute of Mental Health report Ziedonis, D.; Hitsman, B.; Beckham, J. C. Nicotine & Tobacco Research, Vol. 10, Issue 12 https://doi.org/10.1080/14622200802443569	journal	December 2008
Defining and Evaluating Microbial Contributions to Metabolite Variation in Microbiome-Metabolome Association Studies Noecker, Cecilia; Chiu, Hsuan-Chao; McNally, Colin P. mSystems, Vol. 4, Issue 6 https://doi.org/10.1128/msystems.00579-19	journal	December 2019