Metabolic and gut microbiome changes following GLP-1 or dual GLP-1/GLP-2 receptor agonist treatment in diet-induced obese mice

Abstract Enteroendocrine L-cell derived peptide hormones, notably glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2), have become important targets in the treatment of type 2 diabetes, obesity and intestinal diseases. As gut microbial imbalances and maladaptive host responses have b...

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Autores principales:	Mette Simone Aae Madsen, Jacob Bak Holm, Albert Pallejà, Pernille Wismann, Katrine Fabricius, Kristoffer Rigbolt, Martin Mikkelsen, Morten Sommer, Jacob Jelsing, Henrik Bjørn Nielsen, Niels Vrang, Henrik H. Hansen
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7cc76709e4214ac29b3c51f8c12f05a0
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spelling	oai:doaj.org-article:7cc76709e4214ac29b3c51f8c12f05a02021-12-02T15:09:38ZMetabolic and gut microbiome changes following GLP-1 or dual GLP-1/GLP-2 receptor agonist treatment in diet-induced obese mice10.1038/s41598-019-52103-x2045-2322https://doaj.org/article/7cc76709e4214ac29b3c51f8c12f05a02019-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-52103-xhttps://doaj.org/toc/2045-2322Abstract Enteroendocrine L-cell derived peptide hormones, notably glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2), have become important targets in the treatment of type 2 diabetes, obesity and intestinal diseases. As gut microbial imbalances and maladaptive host responses have been implicated in the pathology of obesity and diabetes, this study aimed to determine the effects of pharmacologically stimulated GLP-1 and GLP-2 receptor function on the gut microbiome composition in diet-induced obese (DIO) mice. DIO mice received treatment with a selective GLP-1 receptor agonist (liraglutide, 0.2 mg/kg, BID) or dual GLP-1/GLP-2 receptor agonist (GUB09–145, 0.04 mg/kg, BID) for 4 weeks. Both compounds suppressed caloric intake, promoted a marked weight loss, improved glucose tolerance and reduced plasma cholesterol levels. 16S rDNA sequencing and deep-sequencing shotgun metagenomics was applied for comprehensive within-subject profiling of changes in gut microbiome signatures. Compared to baseline, DIO mice assumed phylogenetically similar gut bacterial compositional changes following liraglutide and GUB09-145 treatment, characterized by discrete shifts in low-abundant species and related bacterial metabolic pathways. The microbiome alterations may potentially associate to the converging biological actions of GLP-1 and GLP-2 receptor signaling on caloric intake, glucose metabolism and lipid handling.Mette Simone Aae MadsenJacob Bak HolmAlbert PallejàPernille WismannKatrine FabriciusKristoffer RigboltMartin MikkelsenMorten SommerJacob JelsingHenrik Bjørn NielsenNiels VrangHenrik H. HansenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-12 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mette Simone Aae Madsen Jacob Bak Holm Albert Pallejà Pernille Wismann Katrine Fabricius Kristoffer Rigbolt Martin Mikkelsen Morten Sommer Jacob Jelsing Henrik Bjørn Nielsen Niels Vrang Henrik H. Hansen Metabolic and gut microbiome changes following GLP-1 or dual GLP-1/GLP-2 receptor agonist treatment in diet-induced obese mice
description	Abstract Enteroendocrine L-cell derived peptide hormones, notably glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2), have become important targets in the treatment of type 2 diabetes, obesity and intestinal diseases. As gut microbial imbalances and maladaptive host responses have been implicated in the pathology of obesity and diabetes, this study aimed to determine the effects of pharmacologically stimulated GLP-1 and GLP-2 receptor function on the gut microbiome composition in diet-induced obese (DIO) mice. DIO mice received treatment with a selective GLP-1 receptor agonist (liraglutide, 0.2 mg/kg, BID) or dual GLP-1/GLP-2 receptor agonist (GUB09–145, 0.04 mg/kg, BID) for 4 weeks. Both compounds suppressed caloric intake, promoted a marked weight loss, improved glucose tolerance and reduced plasma cholesterol levels. 16S rDNA sequencing and deep-sequencing shotgun metagenomics was applied for comprehensive within-subject profiling of changes in gut microbiome signatures. Compared to baseline, DIO mice assumed phylogenetically similar gut bacterial compositional changes following liraglutide and GUB09-145 treatment, characterized by discrete shifts in low-abundant species and related bacterial metabolic pathways. The microbiome alterations may potentially associate to the converging biological actions of GLP-1 and GLP-2 receptor signaling on caloric intake, glucose metabolism and lipid handling.
format	article
author	Mette Simone Aae Madsen Jacob Bak Holm Albert Pallejà Pernille Wismann Katrine Fabricius Kristoffer Rigbolt Martin Mikkelsen Morten Sommer Jacob Jelsing Henrik Bjørn Nielsen Niels Vrang Henrik H. Hansen
author_facet	Mette Simone Aae Madsen Jacob Bak Holm Albert Pallejà Pernille Wismann Katrine Fabricius Kristoffer Rigbolt Martin Mikkelsen Morten Sommer Jacob Jelsing Henrik Bjørn Nielsen Niels Vrang Henrik H. Hansen
author_sort	Mette Simone Aae Madsen
title	Metabolic and gut microbiome changes following GLP-1 or dual GLP-1/GLP-2 receptor agonist treatment in diet-induced obese mice
title_short	Metabolic and gut microbiome changes following GLP-1 or dual GLP-1/GLP-2 receptor agonist treatment in diet-induced obese mice
title_full	Metabolic and gut microbiome changes following GLP-1 or dual GLP-1/GLP-2 receptor agonist treatment in diet-induced obese mice
title_fullStr	Metabolic and gut microbiome changes following GLP-1 or dual GLP-1/GLP-2 receptor agonist treatment in diet-induced obese mice
title_full_unstemmed	Metabolic and gut microbiome changes following GLP-1 or dual GLP-1/GLP-2 receptor agonist treatment in diet-induced obese mice
title_sort	metabolic and gut microbiome changes following glp-1 or dual glp-1/glp-2 receptor agonist treatment in diet-induced obese mice
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/7cc76709e4214ac29b3c51f8c12f05a0
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Metabolic and gut microbiome changes following GLP-1 or dual GLP-1/GLP-2 receptor agonist treatment in diet-induced obese mice

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