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Developmental Signatures of Microbiota-Derived Metabolites in the Mouse Brain

The gut microbiome is recognized to exert a wide-ranging influence on host health and disease, including brain development and behavior. Commensal bacteria can produce bioactive molecules that enter the circulation and impact host physiology and homeostasis. However, little is known about the potent...

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Autores principales: Swann, Jonathan R., Spitzer, Sonia O., Diaz Heijtz, Rochellys
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281085/
https://www.ncbi.nlm.nih.gov/pubmed/32344839
http://dx.doi.org/10.3390/metabo10050172
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author Swann, Jonathan R.
Spitzer, Sonia O.
Diaz Heijtz, Rochellys
author_facet Swann, Jonathan R.
Spitzer, Sonia O.
Diaz Heijtz, Rochellys
author_sort Swann, Jonathan R.
collection PubMed
description The gut microbiome is recognized to exert a wide-ranging influence on host health and disease, including brain development and behavior. Commensal bacteria can produce bioactive molecules that enter the circulation and impact host physiology and homeostasis. However, little is known about the potential for these metabolites to cross the blood–brain barrier and enter the developing brain under normal physiological conditions. In this study, we used a liquid chromatography–mass spectrometry-based metabolomic approach to characterize the developmental profiles of microbial-derived metabolites in the forebrains of mice across three key postnatal developmental stages, co-occurring with the maturation of the gut microbiota. We demonstrate that direct metabolites of the gut microbiome (e.g., imidazole propionate) or products of the combinatorial metabolism between the microbiome and host (e.g., 3-indoxyl-sulfate, trimethylamine-N-oxide, and phenylacetylglycine) are present in the forebrains of mice as early as the neonatal period and remain into adulthood. These findings demonstrate that microbial-associated molecules can cross the BBB either in their detected form or as precursor molecules that undergo further processing in the brain. These chemical messengers are able to bind receptors known to be expressed in the brain. Alterations in the gut microbiome may therefore influence neurodevelopmental trajectories via the regulation of these microbial-associated metabolites.
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spelling pubmed-72810852020-06-15 Developmental Signatures of Microbiota-Derived Metabolites in the Mouse Brain Swann, Jonathan R. Spitzer, Sonia O. Diaz Heijtz, Rochellys Metabolites Article The gut microbiome is recognized to exert a wide-ranging influence on host health and disease, including brain development and behavior. Commensal bacteria can produce bioactive molecules that enter the circulation and impact host physiology and homeostasis. However, little is known about the potential for these metabolites to cross the blood–brain barrier and enter the developing brain under normal physiological conditions. In this study, we used a liquid chromatography–mass spectrometry-based metabolomic approach to characterize the developmental profiles of microbial-derived metabolites in the forebrains of mice across three key postnatal developmental stages, co-occurring with the maturation of the gut microbiota. We demonstrate that direct metabolites of the gut microbiome (e.g., imidazole propionate) or products of the combinatorial metabolism between the microbiome and host (e.g., 3-indoxyl-sulfate, trimethylamine-N-oxide, and phenylacetylglycine) are present in the forebrains of mice as early as the neonatal period and remain into adulthood. These findings demonstrate that microbial-associated molecules can cross the BBB either in their detected form or as precursor molecules that undergo further processing in the brain. These chemical messengers are able to bind receptors known to be expressed in the brain. Alterations in the gut microbiome may therefore influence neurodevelopmental trajectories via the regulation of these microbial-associated metabolites. MDPI 2020-04-25 /pmc/articles/PMC7281085/ /pubmed/32344839 http://dx.doi.org/10.3390/metabo10050172 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Swann, Jonathan R.
Spitzer, Sonia O.
Diaz Heijtz, Rochellys
Developmental Signatures of Microbiota-Derived Metabolites in the Mouse Brain
title Developmental Signatures of Microbiota-Derived Metabolites in the Mouse Brain
title_full Developmental Signatures of Microbiota-Derived Metabolites in the Mouse Brain
title_fullStr Developmental Signatures of Microbiota-Derived Metabolites in the Mouse Brain
title_full_unstemmed Developmental Signatures of Microbiota-Derived Metabolites in the Mouse Brain
title_short Developmental Signatures of Microbiota-Derived Metabolites in the Mouse Brain
title_sort developmental signatures of microbiota-derived metabolites in the mouse brain
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281085/
https://www.ncbi.nlm.nih.gov/pubmed/32344839
http://dx.doi.org/10.3390/metabo10050172
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