Unconjugated bile acids influence expression of circadian genes: a potential mechanism for microbe-host crosstalk

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dc.contributor.author Govindarajan, Kalaimathi
dc.contributor.author MacSharry, John
dc.contributor.author Casey, Pat G.
dc.contributor.author Shanahan, Fergus
dc.contributor.author Joyce, Susan A.
dc.contributor.author Gahan, Cormac G.
dc.date.accessioned 2016-12-09T09:38:34Z
dc.date.available 2016-12-09T09:38:34Z
dc.date.issued 2016-12-01
dc.identifier.citation Govindarajan K., MacSharry J., Casey P. G., Shanahan F., Joyce S. A., and Gahan C. G. M. (2016) ‘Unconjugated Bile Acids Influence Expression of Circadian Genes: A Potential Mechanism for Microbe-Host Crosstalk’, PLoS ONE 11(12): e0167319 (13 pp). doi:10.1371/journal.pone.0167319 en
dc.identifier.volume 11 en
dc.identifier.issued 1212 en
dc.identifier.startpage e0167319-1 en
dc.identifier.endpage e0167319-13 en
dc.identifier.issn 1932-6203
dc.identifier.uri http://hdl.handle.net/10468/3362
dc.identifier.doi 10.1371/journal.pone.0167319
dc.description.abstract 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. 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. en
dc.description.sponsorship Health Research Board Ireland (grant number HRA-POR- 2013-296); Science Foundation Ireland (Grant Number SFI/12/RC/2273) en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher Public Library of Science en
dc.rights © 2016 Govindarajan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. en
dc.rights.uri https://creativecommons.org/licenses/by/4.0/ en
dc.subject Bile en
dc.subject Gene expression en
dc.subject Circadian rhythms en
dc.subject Circadian oscillators en
dc.subject Gene regulation en
dc.subject Caco-2 cells en
dc.subject Oils en
dc.subject Regulator genes en
dc.title Unconjugated bile acids influence expression of circadian genes: a potential mechanism for microbe-host crosstalk en
dc.type Article (peer-reviewed) en
dc.internal.authorcontactother Cormac Gahan, Microbiology, University College Cork, Cork, Ireland. +353-21-490-3000 Email: c.gahan@ucc.ie en
dc.internal.availability Full text available en
dc.date.updated 2016-12-09T09:29:21Z
dc.description.version Published Version en
dc.internal.rssid 375019492
dc.internal.rssid 424083999
dc.contributor.funder Science Foundation Ireland en
dc.contributor.funder Health Research Board en
dc.description.status Peer reviewed en
dc.identifier.journaltitle Plos One en
dc.internal.copyrightchecked No !!CORA!! en
dc.internal.licenseacceptance Yes en
dc.internal.IRISemailaddress c.gahan@ucc.ie en
dc.internal.IRISemailaddress s.joyce@ucc.ie en


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© 2016 Govindarajan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Except where otherwise noted, this item's license is described as © 2016 Govindarajan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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