Unconjugated bile acids influence expression of circadian genes: a potential mechanism for microbe-host crosstalk
| 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.contributor.funder | Science Foundation Ireland | en |
| dc.contributor.funder | Health Research Board | en |
| dc.date.accessioned | 2016-12-09T09:38:34Z | |
| dc.date.available | 2016-12-09T09:38:34Z | |
| dc.date.issued | 2016-12-01 | |
| dc.date.updated | 2016-12-09T09:29:21Z | |
| 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.description.status | Peer reviewed | en |
| dc.description.version | Published Version | en |
| dc.format.mimetype | application/pdf | en |
| 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.doi | 10.1371/journal.pone.0167319 | |
| dc.identifier.endpage | e0167319-13 | en |
| dc.identifier.issn | 1932-6203 | |
| dc.identifier.issued | 1212 | en |
| dc.identifier.journaltitle | Plos One | en |
| dc.identifier.startpage | e0167319-1 | en |
| dc.identifier.uri | https://hdl.handle.net/10468/3362 | |
| dc.identifier.volume | 11 | 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 |
