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.

doi:10.1038/s41598-019-52103-x

Cited by 78 publications

(50 citation statements)

References 81 publications

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“…Moreover, the results were inconsistent among those studies treated with liraglutide, sitagliptin, vildagliptin, and saxagliptin. In terms of β-diversity, there was higher cumulative evidence of significant difference after using metformin (5, 36-39, 41, 43-50, 54-56), and similar results were consistently reported among those studies treated with acarbose (5, 58-61), liraglutide (60,65,66,69,70), sitagliptin (5,60,73), and vildagliptin (6,74) across different mouse models. Evidence for the effects of other drugs was limited ( Table 9).…”

Section: Diversitysupporting

confidence: 67%

“…The potential role of this mucin-degrading bacterium in ameliorating metabolic disorders was further confirmed by a series of animal experiments. For example, mice treated with metformin and liraglutide showed increased levels of A. municiphila in association with improved control of blood glucose and body weight (55,65). More importantly, HFD-fed mice treated with A. municiphila exhibited similar improvements in glucose tolerance and goblet cell production and inflammatory regulations as compared to the metformin treatment group (56).…”

Section: Discussionmentioning

confidence: 98%

“…The genus Akkermanisa (phylum Verrucomicrobia) increased in eight studies treated with metformin using dietary or genetic models (35,37,38,41,44,48,54,56). Three of the four studies with metformin (41,53,55) reported an increase in the species A. muciniphila, and another two studies reported a similar increase in this species after treating with liraglutide (65,68).…”

Section: Bacterial Taxamentioning

confidence: 99%

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Effects of Non-insulin Anti-hyperglycemic Agents on Gut Microbiota: A Systematic Review on Human and Animal Studies

Cao

Hsu

et al. 2020

Front. Endocrinol.

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Background: As growing evidence links gut microbiota with the therapeutic efficacy and side effects of anti-hyperglycemic drugs, this article aims to provide a systematic review of the reciprocal interactions between anti-hyperglycemic drugs and gut microbiota taxa, which underlie the effect of the gut microbiome on diabetic control via bug-host interactions. Method: We followed the PRISMA requirements to perform a systematic review on human vs. animal gut microbiota data in PubMed, SCOPUS, and EMBASE databases, and used Cochrane, ROBIN-I, and SYRCLE tools to assess potential bias risks. The outcomes of assessment were trends on gut microbiota taxa, diversity, and associations with metabolic control (e.g., glucose, lipid) following anti-hyperglycemic treatment. Results: Of 2,804 citations, 64 studies (17/humans; 47/mice) were included. In human studies, seven were randomized trials using metformin or acarbose in obese, pre-diabetes, and type 2 diabetes (T2D) patients. Treatment of pre-diabetes and newly diagnosed T2D patients with metformin or acarbose was associated with decreases in genus of Bacteroides, accompanied by increases in both Bifidobacterium and Lactobacillus. Additionally, T2D patients receiving metformin showed increases in various taxa of the order Enterobacteriales and the species Akkermansia muciniphila. Of seven studies with significant differences in beta-diversity, the incremental specific taxa were associated with the improvement of glucose and lipid profiles. In mice, the effects of metformin on A. muciniphila were similar, but an inverse association with Bacteroides was reported. Animal studies on other anti-hyperglycemic drugs, however, showed substantial variations in results. Cao et al. Anti-hyperglycemic Drugs and Gut Microbiota Conclusions: The changes in specific taxa and β-diversity of gut microbiota were associated with metformin and acarbose in humans while pertinent information for other anti-hyperglycemic drugs could only be obtained in rodent studies. Further human studies on anti-hyperglycemic drugs other than metformin and acarbose are needed to explore gut microbiota's role in their therapeutic efficacies and side effects.

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Section: Diversitysupporting

confidence: 67%

Section: Discussionmentioning

confidence: 98%

Section: Bacterial Taxamentioning

confidence: 99%

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Effects of Non-insulin Anti-hyperglycemic Agents on Gut Microbiota: A Systematic Review on Human and Animal Studies

Cao

Hsu

et al. 2020

Front. Endocrinol.

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“…In fact, disruption of intestinal homeostasis and associated gut microbiome dysbiosis promote T2DM [28], and intensive insulin therapy and oral hypoglycemic agents recover gut microbiome dysbiosis [28][29][30]. In one study, the Firmicutes: Bacteroidetes ratio was reported to be elevated in HFD-fed mice and in obese humans [27]. Our results concur with these findings, although our HFD-fed Px rats were not obese.…”

Section: Discussionsupporting

confidence: 86%

“…Type 2 diabetes alters the gut microbiome, and host-gut microbiome interactions contribute to the efficacies of diabetic drugs [26,27]. In fact, disruption of intestinal homeostasis and associated gut microbiome dysbiosis promote T2DM [28], and intensive insulin therapy and oral hypoglycemic agents recover gut microbiome dysbiosis [28][29][30].…”

Section: Discussionmentioning

confidence: 99%

Acid Hydrolyzed Silk Peptide Consumption Improves Anti-Diabetic Symptoms by Potentiating Insulin Secretion and Preventing Gut Microbiome Dysbiosis in Non-Obese Type 2 Diabetic Animals

et al. 2020

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Silk fibroin hydrolysates have been reported to reduce hyperglycemia, but the mechanism has not been determined in Asian type 2 diabetes (T2DM). We hypothesized that the consumption of acid hydrolyzed silk peptides (SPs) alleviates hyperglycemia by improving insulin sensitivity and subsequently normalizing glucose-stimulated insulin secretion in T2DM. We investigated this hypothesis in a partial pancreatectomized (Px) rat model. Px rats was assigned randomly to the following six groups and fed assigned diet for 8 weeks: the Px-control (0.5 g/kg/day dextrin), the SP-L (0.05 g/kg/day), the SP-M (0.1 g/kg/day), the SP-H (0.5 g/kg/day), the positive-control (40 mg/kg/day metformin), or the normal-control (sham-operated rats; 0.5 g/kg/day dextrin). SPs contained high levels of glycine, alanine, and serine. We found SPs dose-dependently increased food efficiency and body weight gain in Px rats. Animals in the Px-control group rats exhibited lower glucose metabolism, as evidenced by impaired glucose-stimulated insulin secretion coupled with impaired insulin sensitivity, and reduced bone mineral density (BMD) and lean body mass (LBM), compared to the normal-control. SPs and metformin similarly partially protected against Px-induced BMD loss in the lumbar spine and femur. Px-induced decreases in LBM were dose-dependently prevented by SPs, and muscle forces in the SP-M and SP-H groups were maintained at the normal-control level. Glucose tolerance was dose-dependently improved by SPs as determined by oral glucose tolerance and oral maltose tolerance tests, and glucose tolerances were similar in the SP-H and positive-control groups. Insulin tolerance, an index of insulin sensitivity, was dose-dependently enhanced by SPs, and the SP-H group exhibited better insulin tolerance than the positive-control group as determined by intraperitoneal insulin sensitivity testing. Insulin secretory capacity assessed using a hyperglycemic clamp improved in the following order: Px-control <SA-L <SA-M <positive-control <SA-H <normal-control. SP-M prevented gut microbiota dysbiosis. In conclusion, SPs administered at 0.1–0.5 g/kg/day improved glucose regulation by potentiating both insulin secretion and insulin sensitivity in non-obese T2DM rats.

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Madla¹,

Gavins²,

Trenfield³

et al. 2021

Biopharmaceutics

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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

Cited by 78 publications

References 81 publications

Effects of Non-insulin Anti-hyperglycemic Agents on Gut Microbiota: A Systematic Review on Human and Animal Studies

Effects of Non-insulin Anti-hyperglycemic Agents on Gut Microbiota: A Systematic Review on Human and Animal Studies

Acid Hydrolyzed Silk Peptide Consumption Improves Anti-Diabetic Symptoms by Potentiating Insulin Secretion and Preventing Gut Microbiome Dysbiosis in Non-Obese Type 2 Diabetic Animals

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