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

• Published in: Scientific reports Vol. 9; no. 1; pp. 15582 - 12
• Main Authors: Madsen, Mette Simone Aae, Holm, Jacob Bak, Pallejà, Albert, Wismann, Pernille, Fabricius, Katrine, Rigbolt, Kristoffer, Mikkelsen, Martin, Sommer, Morten, Jelsing, Jacob, Nielsen, Henrik Bjørn, Vrang, Niels, Hansen, Henrik H.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 30.10.2019; Nature Publishing Group; Nature Portfolio
• Subjects: 38; 45/22; 45/23; 631/154/436/1729; 631/326/2565/2142; 64/60; Agonists; Animals; Body weight loss; Cholesterol; Diabetes; Diabetes mellitus (non-insulin dependent); Diet; Diet - adverse effects; Digestive system; Gastrointestinal Microbiome - drug effects; Gastrointestinal tract; Glucagon; Glucagon-like peptide 1; Glucagon-like peptide 2; Glucagon-Like Peptide-1 Receptor - agonists; Glucagon-Like Peptide-2 Receptor - agonists; Glucose metabolism; Glucose tolerance; Hormones; Humanities and Social Sciences; Intestinal microflora; Intestine; Lipid metabolism; Liraglutide - pharmacology; Male; Menopause; Metabolic pathways; Metabolism; Metagenome - drug effects; Mice; Mice, Inbred C57BL; Microbiomes; Microbiota; multidisciplinary; Obesity; Obesity - chemically induced; Obesity - drug therapy; Obesity - metabolism; Obesity - microbiology; Peptide hormones; Peptides; Phylogeny; rRNA 16S; Science; Science (multidisciplinary); Weight control
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-52103-x

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.