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Sci Rep. 2017 Oct 19;7(1):13523. doi: 10.1038/s41598-017-14010-x.

Recombinant Incretin-Secreting Microbe Improves Metabolic Dysfunction in High-Fat Diet Fed Rodents.

Author information

1
Teagasc Food Research Centre, Moorepark, Fermoy, Co, Cork, Ireland.
2
School of Microbiology, University College Cork, Co, Cork, Ireland.
3
APC Microbiome Institute, University College Cork, Co, Cork, Ireland.
4
Department of Biological Sciences, Cork Institute of Technology, Co, Cork, Ireland.
5
Department of Neuroscience, University College Cork, Co, Cork, Ireland.
6
Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada.
7
Department of Computing Science, University of Alberta, Edmonton, Alberta, Canada.
8
National Institute for Nanotechnology, Edmonton, Alberta, Canada.
9
Department of Psychiatry, University College Cork, Co, Cork, Ireland.
10
Surgery Departments, University of Michigan, Ann Arbor, MI, USA.
11
Teagasc Food Research Centre, Moorepark, Fermoy, Co, Cork, Ireland. p.ross@ucc.ie.
12
APC Microbiome Institute, University College Cork, Co, Cork, Ireland. p.ross@ucc.ie.

Abstract

The 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.

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