Children with Autism and Their Typically Developing Siblings Differ in Amplicon Sequence Variants and Predicted Functions of Stool-Associated Microbes

ABSTRACT The existence of a link between the gut microbiome and autism spectrum disorder (ASD) is well established in mice, but in human populations, efforts to identify microbial biomarkers have been limited due to a lack of appropriately matched controls, stratification of participants within the...

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Autores principales:	Maude M. David, Christine Tataru, Jena Daniels, Jessey Schwartz, Jessica Keating, Jarrad Hampton-Marcell, Neil Gottel, Jack A. Gilbert, Dennis P. Wall
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2021
Materias:	autism spectrum disorder microbiome crowdsource 16S rRNA gene sequencing Clostridiales Lachnospiraceae Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/3f545ff85d284708989ba10039ce132a
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spelling	oai:doaj.org-article:3f545ff85d284708989ba10039ce132a2021-12-02T19:22:27ZChildren with Autism and Their Typically Developing Siblings Differ in Amplicon Sequence Variants and Predicted Functions of Stool-Associated Microbes10.1128/mSystems.00193-202379-5077https://doaj.org/article/3f545ff85d284708989ba10039ce132a2021-04-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSystems.00193-20https://doaj.org/toc/2379-5077ABSTRACT The existence of a link between the gut microbiome and autism spectrum disorder (ASD) is well established in mice, but in human populations, efforts to identify microbial biomarkers have been limited due to a lack of appropriately matched controls, stratification of participants within the autism spectrum, and sample size. To overcome these limitations, we crowdsourced the recruitment of families with age-matched sibling pairs between 2 and 7 years old (within 2 years of each other), where one child had a diagnosis of ASD and the other did not. Parents collected stool samples, provided a home video of their ASD child’s natural social behavior, and responded online to diet and behavioral questionnaires. 16S rRNA V4 amplicon sequencing of 117 samples (60 ASD and 57 controls) identified 21 amplicon sequence variants (ASVs) that differed significantly between the two cohorts: 11 were found to be enriched in neurotypical children (six ASVs belonging to the Lachnospiraceae family), while 10 were enriched in children with ASD (including Ruminococcaceae and Bacteroidaceae families). Summarizing the expected KEGG orthologs of each predicted genome, the taxonomic biomarkers associated with children with ASD can use amino acids as precursors for butyragenic pathways, potentially altering the availability of neurotransmitters like glutamate and gamma aminobutyric acid (GABA). IMPORTANCE Autism spectrum disorder (ASD), which now affects 1 in 54 children in the United States, is known to have comorbidity with gut disorders of a variety of types; however, the link to the microbiome remains poorly characterized. Recent work has provided compelling evidence to link the gut microbiome to the autism phenotype in mouse models, but identification of specific taxa associated with autism has suffered replicability issues in humans. This has been due in part to sample size that sufficiently covers the spectrum of phenotypes known to autism (which range from subtle to severe) and a lack of appropriately matched controls. Our original study proposes to overcome these limitations by collecting stool-associated microbiome on 60 sibling pairs of children, one with autism and one neurotypically developing, both 2 to 7 years old and no more than 2 years apart in age. We use exact sequence variant analysis and both permutation and differential abundance procedures to identify 21 taxa with significant enrichment or depletion in the autism cohort compared to their matched sibling controls. Several of these 21 biomarkers have been identified in previous smaller studies; however, some are new to autism and known to be important in gut-brain interactions and/or are associated with specific fatty acid biosynthesis pathways.Maude M. DavidChristine TataruJena DanielsJessey SchwartzJessica KeatingJarrad Hampton-MarcellNeil GottelJack A. GilbertDennis P. WallAmerican Society for Microbiologyarticleautism spectrum disordermicrobiomecrowdsource16S rRNA gene sequencingClostridialesLachnospiraceaeMicrobiologyQR1-502ENmSystems, Vol 6, Iss 2 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	autism spectrum disorder microbiome crowdsource 16S rRNA gene sequencing Clostridiales Lachnospiraceae Microbiology QR1-502
spellingShingle	autism spectrum disorder microbiome crowdsource 16S rRNA gene sequencing Clostridiales Lachnospiraceae Microbiology QR1-502 Maude M. David Christine Tataru Jena Daniels Jessey Schwartz Jessica Keating Jarrad Hampton-Marcell Neil Gottel Jack A. Gilbert Dennis P. Wall Children with Autism and Their Typically Developing Siblings Differ in Amplicon Sequence Variants and Predicted Functions of Stool-Associated Microbes
description	ABSTRACT The existence of a link between the gut microbiome and autism spectrum disorder (ASD) is well established in mice, but in human populations, efforts to identify microbial biomarkers have been limited due to a lack of appropriately matched controls, stratification of participants within the autism spectrum, and sample size. To overcome these limitations, we crowdsourced the recruitment of families with age-matched sibling pairs between 2 and 7 years old (within 2 years of each other), where one child had a diagnosis of ASD and the other did not. Parents collected stool samples, provided a home video of their ASD child’s natural social behavior, and responded online to diet and behavioral questionnaires. 16S rRNA V4 amplicon sequencing of 117 samples (60 ASD and 57 controls) identified 21 amplicon sequence variants (ASVs) that differed significantly between the two cohorts: 11 were found to be enriched in neurotypical children (six ASVs belonging to the Lachnospiraceae family), while 10 were enriched in children with ASD (including Ruminococcaceae and Bacteroidaceae families). Summarizing the expected KEGG orthologs of each predicted genome, the taxonomic biomarkers associated with children with ASD can use amino acids as precursors for butyragenic pathways, potentially altering the availability of neurotransmitters like glutamate and gamma aminobutyric acid (GABA). IMPORTANCE Autism spectrum disorder (ASD), which now affects 1 in 54 children in the United States, is known to have comorbidity with gut disorders of a variety of types; however, the link to the microbiome remains poorly characterized. Recent work has provided compelling evidence to link the gut microbiome to the autism phenotype in mouse models, but identification of specific taxa associated with autism has suffered replicability issues in humans. This has been due in part to sample size that sufficiently covers the spectrum of phenotypes known to autism (which range from subtle to severe) and a lack of appropriately matched controls. Our original study proposes to overcome these limitations by collecting stool-associated microbiome on 60 sibling pairs of children, one with autism and one neurotypically developing, both 2 to 7 years old and no more than 2 years apart in age. We use exact sequence variant analysis and both permutation and differential abundance procedures to identify 21 taxa with significant enrichment or depletion in the autism cohort compared to their matched sibling controls. Several of these 21 biomarkers have been identified in previous smaller studies; however, some are new to autism and known to be important in gut-brain interactions and/or are associated with specific fatty acid biosynthesis pathways.
format	article
author	Maude M. David Christine Tataru Jena Daniels Jessey Schwartz Jessica Keating Jarrad Hampton-Marcell Neil Gottel Jack A. Gilbert Dennis P. Wall
author_facet	Maude M. David Christine Tataru Jena Daniels Jessey Schwartz Jessica Keating Jarrad Hampton-Marcell Neil Gottel Jack A. Gilbert Dennis P. Wall
author_sort	Maude M. David
title	Children with Autism and Their Typically Developing Siblings Differ in Amplicon Sequence Variants and Predicted Functions of Stool-Associated Microbes
title_short	Children with Autism and Their Typically Developing Siblings Differ in Amplicon Sequence Variants and Predicted Functions of Stool-Associated Microbes
title_full	Children with Autism and Their Typically Developing Siblings Differ in Amplicon Sequence Variants and Predicted Functions of Stool-Associated Microbes
title_fullStr	Children with Autism and Their Typically Developing Siblings Differ in Amplicon Sequence Variants and Predicted Functions of Stool-Associated Microbes
title_full_unstemmed	Children with Autism and Their Typically Developing Siblings Differ in Amplicon Sequence Variants and Predicted Functions of Stool-Associated Microbes
title_sort	children with autism and their typically developing siblings differ in amplicon sequence variants and predicted functions of stool-associated microbes
publisher	American Society for Microbiology
publishDate	2021
url	https://doaj.org/article/3f545ff85d284708989ba10039ce132a
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Children with Autism and Their Typically Developing Siblings Differ in Amplicon Sequence Variants and Predicted Functions of Stool-Associated Microbes

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