Microbiome and metabolome modifying effects of several cardiovascular disease interventions in apo-E-/- mice

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dc.contributor.author Ryan, Paul M.
dc.contributor.author London, Lis E. E.
dc.contributor.author Bjorndahl, Trent C.
dc.contributor.author Mandal, Rupasri
dc.contributor.author Murphy, Kiera
dc.contributor.author Fitzgerald, Gerald F.
dc.contributor.author Shanahan, Fergus
dc.contributor.author Ross, R. Paul
dc.contributor.author Wishart, David S.
dc.contributor.author Caplice, Noel M.
dc.contributor.author Stanton, Catherine
dc.date.accessioned 2017-03-27T10:32:08Z
dc.date.available 2017-03-27T10:32:08Z
dc.date.issued 2017-03
dc.identifier.citation Ryan, P. M., London, L. E. E., Bjorndahl, T. C., Mandal, R., Murphy, K., Fitzgerald, G. F., Shanahan, F., Ross, R. P., Wishart, D. S., Caplice, N. M. and Stanton, C. (2017) ‘Microbiome and metabolome modifying effects of several cardiovascular disease interventions in apo-E−/− mice’, Microbiome, 5(30), pp: 1-13. doi:10.1186/s40168-017-0246-x en
dc.identifier.volume 5 en
dc.identifier.issued 30 en
dc.identifier.startpage 1 en
dc.identifier.endpage 13 en
dc.identifier.issn 2049-2618
dc.identifier.uri http://hdl.handle.net/10468/3835
dc.identifier.doi 10.1186/s40168-017-0246-x
dc.description.abstract Background: There is strong evidence indicating that gut microbiota have the potential to modify, or be modified by the drugs and nutritional interventions that we rely upon. This study aims to characterize the compositional and functional effects of several nutritional, neutraceutical, and pharmaceutical cardiovascular disease interventions on the gut microbiome, through metagenomic and metabolomic approaches. Apolipoprotein-E-deficient mice were fed for 24 weeks either high-fat/cholesterol diet alone (control, HFC) or high-fat/cholesterol in conjunction with one of three dietary interventions, as follows: plant sterol ester (PSE), oat β-glucan (OBG) and bile salt hydrolase-active Lactobacillus reuteri APC 2587 (BSH), or the drug atorvastatin (STAT). The gut microbiome composition was then investigated, in addition to the host fecal and serum metabolome. Results: We observed major shifts in the composition of the gut microbiome of PSE mice, while OBG and BSH mice displayed more modest fluctuations, and STAT showed relatively few alterations. Interestingly, these compositional effects imparted by PSE were coupled with an increase in acetate and reduction in isovalerate (p < 0.05), while OBG promoted n-butyrate synthesis (p < 0.01). In addition, PSE significantly dampened the microbial production of the proatherogenic precursor compound, trimethylamine (p < 0.05), attenuated cholesterol accumulation, and nearly abolished atherogenesis in the model (p < 0.05). However, PSE supplementation produced the heaviest mice with the greatest degree of adiposity (p < 0.05). Finally, PSE, OBG, and STAT all appeared to have considerable impact on the host serum metabolome, including alterations in several acylcarnitines previously associated with a state of metabolic dysfunction (p < 0.05). Conclusions: We observed functional alterations in microbial and host-derived metabolites, which may have important implications for systemic metabolic health, suggesting that cardiovascular disease interventions may have a significant impact on the microbiome composition and functionality. This study indicates that the gut microbiome-modifying effects of novel therapeutics should be considered, in addition to the direct host effects. en
dc.description.sponsorship Teagasc (Walsh Fellowship); Ireland Canada University Foundation (Dobbin Scholarship); Science Foundation Ireland (SFI Grant Number: SFI/12/RC/2273); Enterprise Ireland (Commercialization Fund Contract Reference: CF/2013/3030A/B) en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher BioMed Central en
dc.rights © 2017, the Authors. Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. en
dc.rights.uri https://creativecommons.org/licenses/by/4.0/ en
dc.subject Apo-E-deficient en
dc.subject Atherosclerosis en
dc.subject Cardiovascular disease en
dc.subject Microbiome en
dc.subject Metabolome en
dc.title Microbiome and metabolome modifying effects of several cardiovascular disease interventions in apo-E-/- mice en
dc.type Article (peer-reviewed) en
dc.internal.authorcontactother Gerald F. Fitzgerald, Microbiology, University College Cork, Cork, Ireland. +353-21-490-3000 Email: g.fitzgerald@ucc.ie en
dc.internal.availability Full text available en
dc.date.updated 2017-03-27T09:07:51Z
dc.description.version Published Version en
dc.internal.rssid 388762686
dc.contributor.funder Teagasc en
dc.contributor.funder Science Foundation Ireland en
dc.contributor.funder Enterprise Ireland en
dc.contributor.funder Ireland Canada University Foundation
dc.description.status Peer reviewed en
dc.identifier.journaltitle Microbiome en
dc.internal.copyrightchecked Yes en
dc.internal.licenseacceptance Yes en
dc.internal.IRISemailaddress g.fitzgerald@ucc.ie en


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© 2017, the Authors. Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Except where otherwise noted, this item's license is described as © 2017, the Authors. Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
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