An enriched biosignature of gut microbiota-dependent metabolites characterizes maternal plasma in a mouse model of fetal alcohol spectrum disorder

Abstract Prenatal alcohol exposure (PAE) causes permanent cognitive disability. The enteric microbiome generates microbial-dependent products (MDPs) that may contribute to disorders including autism, depression, and anxiety; it is unknown whether similar alterations occur in PAE. Using a mouse PAE m...

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Autores principales:	Manjot S. Virdee, Nipun Saini, Colin D. Kay, Andrew P. Neilson, Sze Ting Cecilia Kwan, Kaylee K. Helfrich, Sandra M. Mooney, Susan M. Smith
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1e4ce84490a14fa496258623b47d85b3
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spelling	oai:doaj.org-article:1e4ce84490a14fa496258623b47d85b32021-12-02T15:08:22ZAn enriched biosignature of gut microbiota-dependent metabolites characterizes maternal plasma in a mouse model of fetal alcohol spectrum disorder10.1038/s41598-020-80093-82045-2322https://doaj.org/article/1e4ce84490a14fa496258623b47d85b32021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-80093-8https://doaj.org/toc/2045-2322Abstract Prenatal alcohol exposure (PAE) causes permanent cognitive disability. The enteric microbiome generates microbial-dependent products (MDPs) that may contribute to disorders including autism, depression, and anxiety; it is unknown whether similar alterations occur in PAE. Using a mouse PAE model, we performed untargeted metabolome analyses upon the maternal–fetal dyad at gestational day 17.5. Hierarchical clustering by principal component analysis and Pearson’s correlation of maternal plasma (813 metabolites) both identified MDPs as significant predictors for PAE. The majority were phenolic acids enriched in PAE. Correlational network analyses revealed that alcohol altered plasma MDP-metabolite relationships, and alcohol-exposed maternal plasma was characterized by a subnetwork dominated by phenolic acids. Twenty-nine MDPs were detected in fetal liver and sixteen in fetal brain, where their impact is unknown. Several of these, including 4-ethylphenylsulfate, oxindole, indolepropionate, p-cresol sulfate, catechol sulfate, and salicylate, are implicated in other neurological disorders. We conclude that MDPs constitute a characteristic biosignature that distinguishes PAE. These MDPs are abundant in human plasma, where they influence physiology and disease. Their altered abundance here may reflect alcohol’s known effects on microbiota composition and gut permeability. We propose that the maternal microbiome and its MDPs are a previously unrecognized influence upon the pathologies that typify PAE.Manjot S. VirdeeNipun SainiColin D. KayAndrew P. NeilsonSze Ting Cecilia KwanKaylee K. HelfrichSandra M. MooneySusan M. SmithNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Manjot S. Virdee Nipun Saini Colin D. Kay Andrew P. Neilson Sze Ting Cecilia Kwan Kaylee K. Helfrich Sandra M. Mooney Susan M. Smith An enriched biosignature of gut microbiota-dependent metabolites characterizes maternal plasma in a mouse model of fetal alcohol spectrum disorder
description	Abstract Prenatal alcohol exposure (PAE) causes permanent cognitive disability. The enteric microbiome generates microbial-dependent products (MDPs) that may contribute to disorders including autism, depression, and anxiety; it is unknown whether similar alterations occur in PAE. Using a mouse PAE model, we performed untargeted metabolome analyses upon the maternal–fetal dyad at gestational day 17.5. Hierarchical clustering by principal component analysis and Pearson’s correlation of maternal plasma (813 metabolites) both identified MDPs as significant predictors for PAE. The majority were phenolic acids enriched in PAE. Correlational network analyses revealed that alcohol altered plasma MDP-metabolite relationships, and alcohol-exposed maternal plasma was characterized by a subnetwork dominated by phenolic acids. Twenty-nine MDPs were detected in fetal liver and sixteen in fetal brain, where their impact is unknown. Several of these, including 4-ethylphenylsulfate, oxindole, indolepropionate, p-cresol sulfate, catechol sulfate, and salicylate, are implicated in other neurological disorders. We conclude that MDPs constitute a characteristic biosignature that distinguishes PAE. These MDPs are abundant in human plasma, where they influence physiology and disease. Their altered abundance here may reflect alcohol’s known effects on microbiota composition and gut permeability. We propose that the maternal microbiome and its MDPs are a previously unrecognized influence upon the pathologies that typify PAE.
format	article
author	Manjot S. Virdee Nipun Saini Colin D. Kay Andrew P. Neilson Sze Ting Cecilia Kwan Kaylee K. Helfrich Sandra M. Mooney Susan M. Smith
author_facet	Manjot S. Virdee Nipun Saini Colin D. Kay Andrew P. Neilson Sze Ting Cecilia Kwan Kaylee K. Helfrich Sandra M. Mooney Susan M. Smith
author_sort	Manjot S. Virdee
title	An enriched biosignature of gut microbiota-dependent metabolites characterizes maternal plasma in a mouse model of fetal alcohol spectrum disorder
title_short	An enriched biosignature of gut microbiota-dependent metabolites characterizes maternal plasma in a mouse model of fetal alcohol spectrum disorder
title_full	An enriched biosignature of gut microbiota-dependent metabolites characterizes maternal plasma in a mouse model of fetal alcohol spectrum disorder
title_fullStr	An enriched biosignature of gut microbiota-dependent metabolites characterizes maternal plasma in a mouse model of fetal alcohol spectrum disorder
title_full_unstemmed	An enriched biosignature of gut microbiota-dependent metabolites characterizes maternal plasma in a mouse model of fetal alcohol spectrum disorder
title_sort	enriched biosignature of gut microbiota-dependent metabolites characterizes maternal plasma in a mouse model of fetal alcohol spectrum disorder
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/1e4ce84490a14fa496258623b47d85b3
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An enriched biosignature of gut microbiota-dependent metabolites characterizes maternal plasma in a mouse model of fetal alcohol spectrum disorder

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