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

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dc.contributor.authorRyan, Paul M.
dc.contributor.authorLondon, Lis E. E.
dc.contributor.authorBjorndahl, Trent C.
dc.contributor.authorMandal, Rupasri
dc.contributor.authorMurphy, Kiera
dc.contributor.authorFitzgerald, Gerald F.
dc.contributor.authorShanahan, Fergus
dc.contributor.authorRoss, R. Paul
dc.contributor.authorWishart, David S.
dc.contributor.authorCaplice, Noel M.
dc.contributor.authorStanton, Catherine
dc.contributor.funderTeagascen
dc.contributor.funderScience Foundation Irelanden
dc.contributor.funderEnterprise Irelanden
dc.contributor.funderIreland Canada University Foundation
dc.date.accessioned2017-03-27T10:32:08Z
dc.date.available2017-03-27T10:32:08Z
dc.date.issued2017-03
dc.date.updated2017-03-27T09:07:51Z
dc.description.abstractBackground: 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.sponsorshipTeagasc (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.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationRyan, 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-xen
dc.identifier.doi10.1186/s40168-017-0246-x
dc.identifier.endpage13en
dc.identifier.issn2049-2618
dc.identifier.issued30en
dc.identifier.journaltitleMicrobiomeen
dc.identifier.startpage1en
dc.identifier.urihttps://hdl.handle.net/10468/3835
dc.identifier.volume5en
dc.language.isoenen
dc.publisherBioMed Centralen
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.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subjectApo-E-deficienten
dc.subjectAtherosclerosisen
dc.subjectCardiovascular diseaseen
dc.subjectMicrobiomeen
dc.subjectMetabolomeen
dc.titleMicrobiome and metabolome modifying effects of several cardiovascular disease interventions in apo-E-/- miceen
dc.typeArticle (peer-reviewed)en
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