Recombinant incretin-secreting microbe improves metabolic dysfunction in high-fat diet fed rodents

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dc.contributor.authorRyan, Paul M.
dc.contributor.authorPatterson, Elaine
dc.contributor.authorKent, Robert M.
dc.contributor.authorStack, Helena
dc.contributor.authorO'Connor, Paula M.
dc.contributor.authorMurphy, Kiera
dc.contributor.authorPeterson, Veronica L.
dc.contributor.authorMandal, Rupasri
dc.contributor.authorWishart, David S.
dc.contributor.authorDinan, Timothy G.
dc.contributor.authorCryan, John F.
dc.contributor.authorSeeley, Randy J.
dc.contributor.authorStanton, Catherine
dc.contributor.authorRoss, R. Paul
dc.contributor.funderScience Foundation Ireland
dc.contributor.funderIreland Canada University Foundation
dc.contributor.funderTeagasc
dc.date.accessioned2018-02-06T13:36:27Z
dc.date.available2018-02-06T13:36:27Z
dc.date.issued2017
dc.description.abstractThe gut hormone glucagon-like peptide (GLP)-1 and its analogues represent a new generation of anti-diabetic drugs, which have also demonstrated propensity to modulate host lipid metabolism. Despite this, drugs of this nature are currently limited to intramuscular administration routes due to intestinal degradation. The aim of this study was to design a recombinant microbial delivery vector for a GLP-1 analogue and assess the efficacy of the therapeutic in improving host glucose, lipid and cholesterol metabolism in diet induced obese rodents. Diet-induced obese animals received either Lactobacillus paracasei NFBC 338 transformed to express a long-acting analogue of GLP-1 or the isogenic control microbe which solely harbored the pNZ44 plasmid. Short-term GLP-1 microbe intervention in rats reduced serum low-density lipoprotein cholesterol, triglycerides and triglyceride-rich lipoprotein cholesterol substantially. Conversely, extended GLP-1 microbe intervention improved glucose-dependent insulin secretion, glucose metabolism and cholesterol metabolism, compared to the high-fat control group. Interestingly, the microbe significantly attenuated the adiposity associated with the model and altered the serum lipidome, independently of GLP-1 secretion. These data indicate that recombinant incretin-secreting microbes may offer a novel and safe means of managing cholesterol metabolism and diet induced dyslipidaemia, as well as insulin sensitivity in metabolic dysfunction.en
dc.description.sponsorshipTeagasc (Walsh Fellow Short-term Overseas Training Award)en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.articleid13523
dc.identifier.citationRyan, P. M., Patterson, E., Kent, R. M., Stack, H., O’Connor, P. M., Murphy, K., Peterson, V. L., Mandal, R., Wishart, D. S., Dinan, T. G., Cryan, J. F., Seeley, R. J., Stanton, C. and Ross, R. P. (2017) 'Recombinant incretin-secreting microbe improves metabolic dysfunction in high-fat diet fed rodents', Scientific Reports, 7(1), 13523 (12pp). doi: 10.1038/s41598-017-14010-xen
dc.identifier.doi10.1038/s41598-017-14010-x
dc.identifier.endpage12
dc.identifier.issn2045-2322
dc.identifier.journaltitleScientific Reportsen
dc.identifier.startpage1
dc.identifier.urihttps://hdl.handle.net/10468/5382
dc.identifier.volume7
dc.language.isoenen
dc.publisherNature Publishing Groupen
dc.relation.projectinfo:eu-repo/grantAgreement/SFI/SFI Research Centres/12/RC/2273/IE/Alimentary Pharmabiotic Centre (APC) - Interfacing Food & Medicine/
dc.relation.urihttps://www.nature.com/articles/s41598-017-14010-x
dc.rights© 2017, the authors. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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. Te images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectGlucagon-like peptide-1en
dc.subjectType-2 diabetes-mellitusen
dc.subjectGut microbiotaen
dc.subjectLactococcus-lactisen
dc.subjectLipid-metabolismen
dc.subjectHealthy humansen
dc.subjectBacteriaen
dc.subjectExenatideen
dc.subjectGLP-1en
dc.subjectElevationsen
dc.titleRecombinant incretin-secreting microbe improves metabolic dysfunction in high-fat diet fed rodentsen
dc.typeArticle (peer-reviewed)en
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