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

Mette Simone Aae Madsen, Jacob Bak Holm, Albert Pallejà, Pernille Wismann, Katrine Fabricius, Kristoffer Rigbolt, Martin Tue Mikkelsen, Morten Otto Alexander Sommer, Jacob Jelsing, Henrik Bjørn Nielsen, Niels Vrang, Henrik H Hansen

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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.
Original languageEnglish
Article number15582
JournalScientific Reports
Volume9
ISSN2045-2322
DOIs
Publication statusPublished - 2019

Cite this

Madsen, Mette Simone Aae ; Holm, Jacob Bak ; Pallejà, Albert ; Wismann, Pernille ; Fabricius, Katrine ; Rigbolt, Kristoffer ; Mikkelsen, Martin Tue ; Sommer, Morten Otto Alexander ; Jelsing, Jacob ; Nielsen, Henrik Bjørn ; Vrang, Niels ; Hansen, Henrik H. / Metabolic and gut microbiome changes following GLP-1 or dual GLP-1/GLP-2 receptor agonist treatment in diet-induced obese mice. In: Scientific Reports. 2019 ; Vol. 9.
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title = "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 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.",
author = "Madsen, {Mette Simone Aae} and Holm, {Jacob Bak} and Albert Pallej{\`a} and Pernille Wismann and Katrine Fabricius and Kristoffer Rigbolt and Mikkelsen, {Martin Tue} and Sommer, {Morten Otto Alexander} and Jacob Jelsing and Nielsen, {Henrik Bj{\o}rn} and Niels Vrang and Hansen, {Henrik H}",
year = "2019",
doi = "10.1038/s41598-019-52103-x",
language = "English",
volume = "9",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",

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Madsen, MSA, Holm, JB, Pallejà, A, Wismann, P, Fabricius, K, Rigbolt, K, Mikkelsen, MT, Sommer, MOA, Jelsing, J, Nielsen, HB, Vrang, N & Hansen, HH 2019, 'Metabolic and gut microbiome changes following GLP-1 or dual GLP-1/GLP-2 receptor agonist treatment in diet-induced obese mice', Scientific Reports, vol. 9, 15582. https://doi.org/10.1038/s41598-019-52103-x

Metabolic and gut microbiome changes following GLP-1 or dual GLP-1/GLP-2 receptor agonist treatment in diet-induced obese mice. / Madsen, Mette Simone Aae; Holm, Jacob Bak; Pallejà, Albert; Wismann, Pernille; Fabricius, Katrine; Rigbolt, Kristoffer; Mikkelsen, Martin Tue; Sommer, Morten Otto Alexander; Jelsing, Jacob; Nielsen, Henrik Bjørn; Vrang, Niels; Hansen, Henrik H.

In: Scientific Reports, Vol. 9, 15582, 2019.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Metabolic and gut microbiome changes following GLP-1 or dual GLP-1/GLP-2 receptor agonist treatment in diet-induced obese mice

AU - Madsen, Mette Simone Aae

AU - Holm, Jacob Bak

AU - Pallejà, Albert

AU - Wismann, Pernille

AU - Fabricius, Katrine

AU - Rigbolt, Kristoffer

AU - Mikkelsen, Martin Tue

AU - Sommer, Morten Otto Alexander

AU - Jelsing, Jacob

AU - Nielsen, Henrik Bjørn

AU - Vrang, Niels

AU - Hansen, Henrik H

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

U2 - 10.1038/s41598-019-52103-x

DO - 10.1038/s41598-019-52103-x

M3 - Journal article

C2 - 31666597

VL - 9

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

M1 - 15582

ER -