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Unconjugated Bile Acids Influence Expression of Circadian Genes: A Potential Mechanism for Microbe-Host Crosstalk

Disruptions to circadian rhythm in mice and humans have been associated with an increased risk of obesity and metabolic syndrome. The gut microbiota is known to be essential for the maintenance of circadian rhythm in the host suggesting a role for microbe-host interactions in the regulation of the p...

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Autores principales: Govindarajan, Kalaimathi, MacSharry, John, Casey, Patrick G., Shanahan, Fergus, Joyce, Susan A., Gahan, Cormac G. M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5132238/
https://www.ncbi.nlm.nih.gov/pubmed/27907092
http://dx.doi.org/10.1371/journal.pone.0167319
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author Govindarajan, Kalaimathi
MacSharry, John
Casey, Patrick G.
Shanahan, Fergus
Joyce, Susan A.
Gahan, Cormac G. M.
author_facet Govindarajan, Kalaimathi
MacSharry, John
Casey, Patrick G.
Shanahan, Fergus
Joyce, Susan A.
Gahan, Cormac G. M.
author_sort Govindarajan, Kalaimathi
collection PubMed
description Disruptions to circadian rhythm in mice and humans have been associated with an increased risk of obesity and metabolic syndrome. The gut microbiota is known to be essential for the maintenance of circadian rhythm in the host suggesting a role for microbe-host interactions in the regulation of the peripheral circadian clock. Previous work suggested a role for gut bacterial bile salt hydrolase (BSH) activity in the regulation of host circadian gene expression. Here we demonstrate that unconjugated bile acids, known to be generated through the BSH activity of the gut microbiota, are potentially chronobiological regulators of host circadian gene expression. We utilised a synchronised Caco-2 epithelial colorectal cell model and demonstrated that unconjugated bile acids, but not the equivalent tauro-conjugated bile salts, enhance the expression levels of genes involved in circadian rhythm. In addition oral administration of mice with unconjugated bile acids significantly altered expression levels of circadian clock genes in the ileum and colon as well as the liver with significant changes to expression of hepatic regulators of circadian rhythm (including Dbp) and associated genes (Per2, Per3 and Cry2). The data demonstrate a potential mechanism for microbe-host crosstalk that significantly impacts upon host circadian gene expression.
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spelling pubmed-51322382016-12-21 Unconjugated Bile Acids Influence Expression of Circadian Genes: A Potential Mechanism for Microbe-Host Crosstalk Govindarajan, Kalaimathi MacSharry, John Casey, Patrick G. Shanahan, Fergus Joyce, Susan A. Gahan, Cormac G. M. PLoS One Research Article Disruptions to circadian rhythm in mice and humans have been associated with an increased risk of obesity and metabolic syndrome. The gut microbiota is known to be essential for the maintenance of circadian rhythm in the host suggesting a role for microbe-host interactions in the regulation of the peripheral circadian clock. Previous work suggested a role for gut bacterial bile salt hydrolase (BSH) activity in the regulation of host circadian gene expression. Here we demonstrate that unconjugated bile acids, known to be generated through the BSH activity of the gut microbiota, are potentially chronobiological regulators of host circadian gene expression. We utilised a synchronised Caco-2 epithelial colorectal cell model and demonstrated that unconjugated bile acids, but not the equivalent tauro-conjugated bile salts, enhance the expression levels of genes involved in circadian rhythm. In addition oral administration of mice with unconjugated bile acids significantly altered expression levels of circadian clock genes in the ileum and colon as well as the liver with significant changes to expression of hepatic regulators of circadian rhythm (including Dbp) and associated genes (Per2, Per3 and Cry2). The data demonstrate a potential mechanism for microbe-host crosstalk that significantly impacts upon host circadian gene expression. Public Library of Science 2016-12-01 /pmc/articles/PMC5132238/ /pubmed/27907092 http://dx.doi.org/10.1371/journal.pone.0167319 Text en © 2016 Govindarajan et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Govindarajan, Kalaimathi
MacSharry, John
Casey, Patrick G.
Shanahan, Fergus
Joyce, Susan A.
Gahan, Cormac G. M.
Unconjugated Bile Acids Influence Expression of Circadian Genes: A Potential Mechanism for Microbe-Host Crosstalk
title Unconjugated Bile Acids Influence Expression of Circadian Genes: A Potential Mechanism for Microbe-Host Crosstalk
title_full Unconjugated Bile Acids Influence Expression of Circadian Genes: A Potential Mechanism for Microbe-Host Crosstalk
title_fullStr Unconjugated Bile Acids Influence Expression of Circadian Genes: A Potential Mechanism for Microbe-Host Crosstalk
title_full_unstemmed Unconjugated Bile Acids Influence Expression of Circadian Genes: A Potential Mechanism for Microbe-Host Crosstalk
title_short Unconjugated Bile Acids Influence Expression of Circadian Genes: A Potential Mechanism for Microbe-Host Crosstalk
title_sort unconjugated bile acids influence expression of circadian genes: a potential mechanism for microbe-host crosstalk
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5132238/
https://www.ncbi.nlm.nih.gov/pubmed/27907092
http://dx.doi.org/10.1371/journal.pone.0167319
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