Dataset Information

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.

SUBMITTER: Madsen MSA

PROVIDER: S-EPMC6821799 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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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.

Madsen Mette Simone Aae MSA Holm Jacob Bak JB Pallejà Albert A Wismann Pernille P Fabricius Katrine K Rigbolt Kristoffer K Mikkelsen Martin M Sommer Morten M Jelsing Jacob J Nielsen Henrik Bjørn HB Vrang Niels N Hansen Henrik H HH

Scientific reports 20191030 1

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-in ...[more]

PMID: 31666597

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Project description:ObjectiveThe gut microbiota is an important influencing factor of metabolic health. Although dietary interventions with probiotics, prebiotics, and synbiotics can be effective means to regulate obesity and associated comorbidities, the underlying shifts in gut microbial communities, especially at the functional level, have not been characterized in great details. In this study, we sought to investigate the effects of synbiotics on the regulation of gut microbiota and the alleviation of high-fat diet (HFD)-induced metabolic disorders in mice.MethodsSpecific pathogen-free (SPF) male C57BL/6J mice were fed diets with either 10% (normal diet, ND) or 60% (high-fat diet, HFD) of total calories from fat (lard). Dietary interventions in the HFD-fed mice included (i) probiotic (Bifidobacterium animalis subsp. lactis and Lactobacillus paracasei subsp. paracasei DSM 46331), (ii) prebiotic (oat β-glucan), and (iii) synbiotic (a mixture of i and ii) treatments for 12 weeks. Besides detailed characterization of host metabolic parameters, a multi-omics approach was used to systematically profile the microbial signatures at both the phylogenetic and functional levels using 16S rRNA gene sequencing, metaproteomics and targeted metabolomics analysis.ResultsThe synbiotic intervention significantly reduced body weight gain and alleviated features of metabolic complications. At the phylogenetic level, the synbiotic treatment significantly reversed HFD-induced changes in microbial populations, both in terms of richness and the relative abundance of specific taxa. Potentially important species such as Faecalibaculum rodentium and Alistipes putredinis that might mediate the beneficial effects of the synbiotic were identified. At the functional level, short-chain fatty acid and bile acid profiles revealed that all dietary interventions significantly restored cecal levels of acetate, propionate, and butyrate, while the synbiotic treatment reduced the bile acid pools most efficiently. Metaproteomics revealed that the effects of the synbiotic intervention might be mediated through metabolic pathways involved in carbohydrate, amino acid, and energy metabolisms.ConclusionsOur results suggested that dietary intervention using the novel synbiotic can alleviate HFD-induced weight gain and restore gut microbial ecosystem homeostasis phylogenetically and functionally.

Project description:BACKGROUND:Human gut microbiome has an essential role in human health and disease. Although the major dominant microbiota within individuals have been reported, the change of gut microbiome caused by external factors, such as antibiotic use and bowel cleansing, remains unclear. We conducted this study to investigate the change of gut microbiome in overweight male adults after bowel preparation, where none of the participants had been diagnosed with any systemic diseases. METHODS:A total of 20 overweight, male Taiwanese adults were recruited, and all participants were omnivorous. The participants provided fecal samples and blood samples at three time points: prior to bowel preparation, 7?days after colonoscopy, and 28?days after colonoscopy. The microbiota composition in fecal samples was analyzed using 16S ribosome RNA gene amplicon sequencing. RESULTS:Our results demonstrated that the relative abundance of the most dominant bacteria hardly changed from prior to bowel preparation to 28?days after colonoscopy. Using the ratio of Prevotella to the sum of Prevotella and Bacteroides in the fecal samples at baseline, the participants were separated into two groups. The fecal samples of the Type 1 group was Bacteroides-dominant, and that of the Type 2 group was Prevotella-dominant with a noticeable presence Bacteroides. Bulleidia appears more in the Type 1 fecal samples, while Akkermensia appears more in the Type 2 fecal samples. Of each type, the gut microbial diversity differed slightly among the three collection times. Additionally, the Type 2 fecal microbiota was temporarily susceptible to bowel cleansing. Predictive functional analysis of microbial community reveals that their activities for the mineral absorption metabolism and arachidonic acid metabolism differed significantly between the two types. Depending on their fecal type, the variance of triglycerides and C-reactive protein also differed between the two types of participants. CONCLUSIONS:Depending upon the fecal type, the microbial diversity and the predictive functional modules of microbial community differed significantly after bowel preparation. In addition, blood biochemical markers presented somewhat associated with fecal type. Therefore, our results might provide some insights as to how knowledge of the microbial community could be used to promote health through personalized clinical treatment.

Dataset Information

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

Publications

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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