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Please use this identifier to cite or link to this item: http://hdl.handle.net/11019/1113

Title: Microbiome and metabolome modifying effects of several cardiovascular disease interventions in apo-E−/− mice
Authors: Ryan, Paul M
London, Lis E E
Bjorndahl, Trent C
Mandal, Rupasri
Murphy, Kiera
Fitzgerald, Gerald F
Shanahan, Fergus
Ross, R. Paul
Wishart, David S
Caplice, Noel M
Stanton, Catherine
Keywords: Apo-E-deficient
Atherosclerosis
Cardiovascular disease
Microbiome
Metabolome
Issue Date: 13-Mar-2017
Publisher: Biomed Central
Citation: Ryan et al. Microbiome and metabolome modifying effects of several cardiovascular disease interventions in apo-E−/− mice . Microbiome. 2017 Mar 13;5(1):30. DOI: 10.1186/s40168-017-0246-x
Series/Report no.: Microbiome;vol 5
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.
Description: peer-reviewed
Paul M. Ryan is in receipt of a Teagasc Walsh Fellowship. Travel support was awarded to Paul M. Ryan by the Ireland Canada University Foundation (ICUF) Dobbin Scholarship and the Teagasc Walsh Fellow Short-term Overseas Training Scheme for work carried out in The Metabolomics Innovation Centre (TMIC), University of Alberta. This work is supported by The APC Microbiome Institute (under Science Foundation Ireland [SFI] grant number: SFI/12/RC/2273) and by Enterprise Ireland Commercialization Fund (contract reference: CF/2013/3030A/B).
URI: http://hdl.handle.net/11019/1113
http://dx.doi.org/10.1186/s40168-017-0246-x
Appears in Collections:Teagasc publications in Biomed Central
Food Biosciences

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