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

dc.contributor.authorGovindarajan, Kalaimathi
dc.contributor.authorMacSharry, John
dc.contributor.authorCasey, Pat G.
dc.contributor.authorShanahan, Fergus
dc.contributor.authorJoyce, Susan A.
dc.contributor.authorGahan, Cormac G.
dc.contributor.funderScience Foundation Irelanden
dc.contributor.funderHealth Research Boarden
dc.date.accessioned2016-12-09T09:38:34Z
dc.date.available2016-12-09T09:38:34Z
dc.date.issued2016-12-01
dc.date.updated2016-12-09T09:29:21Z
dc.description.abstractDisruptions 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.sponsorshipHealth Research Board Ireland (grant number HRA-POR- 2013-296); Science Foundation Ireland (Grant Number SFI/12/RC/2273)en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationGovindarajan 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.0167319en
dc.identifier.doi10.1371/journal.pone.0167319
dc.identifier.endpagee0167319-13en
dc.identifier.issn1932-6203
dc.identifier.issued1212en
dc.identifier.journaltitlePlos Oneen
dc.identifier.startpagee0167319-1en
dc.identifier.urihttps://hdl.handle.net/10468/3362
dc.identifier.volume11en
dc.language.isoenen
dc.publisherPublic Library of Scienceen
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.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subjectBileen
dc.subjectGene expressionen
dc.subjectCircadian rhythmsen
dc.subjectCircadian oscillatorsen
dc.subjectGene regulationen
dc.subjectCaco-2 cellsen
dc.subjectOilsen
dc.subjectRegulator genesen
dc.titleUnconjugated bile acids influence expression of circadian genes: a potential mechanism for microbe-host crosstalken
dc.typeArticle (peer-reviewed)en
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