Astragalus compound oral solution synergistically enhances health-promoting effect of metformin in type 2 diabetes mouse model

Zhou, Zekun; Yao, Lu; Li, Jifu; An, Yuchen; Jiang, Wei; Wang, Zengli

doi:10.21203/rs.3.rs-2505907/v1

Cited by 2 publications

(2 citation statements)

References 47 publications

(18 reference statements)

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“…This would be in accordance with supplementation of butyrate limiting hyperglycemia through the regulation of amongst glucagon-like peptide-1 (GLP-1) and insulin in serum 77 . This is further supported by Allobaculum being reported to be positive correlated to hypoglycemia and negative correlated to HOMA-IR levels 78 (not yet peerreviewed). Taken together, the current understanding of the role of Allobaculum on metabolic syndrome supports our observations of improved glucose regulation for the FVT-ChP treated mice that had increased relative abundance of Allobaculum compared with obese control (Fig.…”

Section: Discussionmentioning

confidence: 73%

Transfer of modified fecal viromes improve blood glucose regulation and alleviates symptoms of metabolic dysfunction-associated fatty liver disease in an obesity male mouse model

Mao

Larsen

Zachariassen

et al. 2023

Preprint

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Introduction: Recent evidence suggest a link between gut microbiome dysbiosis and metabolic syndrome, including type-2-diabetes, obesity, and non-alcoholic fatty liver disease (NAFLD). Fecal microbiota transplantation (FMT) has been explored as a way to restore a healthy gut microbiome in obese patients but poses safety concerns. The wide use of FMT is limited by safety concerns about transferring the entire fecal microbiome from one individual to another. Fecal virome transplantation (FVT) is a safer alternative that transfers bacteriophages without bacterial transfer, but still carries the risk of eukaryotic virus infection. Therefore, a safer and more effective tool for modulating gut microbiome is needed. Methods: We explored the potential of implementing three alternative FVT techniques with increased safety established in a recent study (eukaryotic viruses were either eliminated or inactivated) to ameliorate symptoms associated with a diet-induced obesity mouse model. Male mice were fed with an ad libitum high-fat diet before being euthanized (23 weeks of age) and received the different FVT treatments twice with one week of interval. Body weight was measured, oral glucose tests were performed, feces were sampled frequently, and liver, fat pads, mesenteric lymph node, and blood serum were sampled at termination of study. Results: FVT treatments had no effect on weight gain or the amount of epididymal white adipose tissue. Mice given regular untreated FVT (FVT-UnT) had a significant (p < 0.05) drop in the pathological score of their liver tissue when compared to HFD-control mice. Mice treated with a chemostat propagated fecal virome (FVT-ChP, eukaryotic viruses eliminated by dilution) improved their blood glucose regulation significantly (p < 0.05) compared to HFD-control mice. Gut microbiome analysis of both the bacterial and viral component suggested that bacteriophage-mediated modulation of the gut microbiome could be a driving factor for the observed effects. Conclusions: These results may lay the ground to develop safer bacteriophage-based therapeutic tools to restore the dysbiotic gut microbiome associated with metabolic syndrome.

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Section: Discussionmentioning

confidence: 73%

Transfer of modified fecal viromes improve blood glucose regulation and alleviates symptoms of metabolic dysfunction-associated fatty liver disease in an obesity male mouse model

Mao

Larsen

Zachariassen

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…This would be in accordance with supplementation of butyrate limiting hyperglycemia through the regulation of amongst glucagon-like peptide-1 (GLP-1) and insulin in serum 77 . This is further supported by Allobaculum being reported to be positive correlated to hypoglycemia and negative correlated to HOMA-IR levels 78 (not yet peer-reviewed). Taken together, the current understanding of the role of Allobaculum on metabolic syndrome supports our observations of improved glucose regulation for the FVT-ChP treated mice that had increased relative abundance of Allobaculum compared with obese control (Fig.…”

Section: Discussionmentioning

confidence: 70%

Transfer of modified gut viromes improves symptoms associated with metabolic syndrome in obese male mice

Mao,

Larsen,

Zachariassen

et al. 2024

Nat Commun

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Metabolic syndrome encompasses amongst other conditions like obesity and type-2 diabetes and is associated with gut microbiome (GM) dysbiosis. Fecal microbiota transplantation (FMT) has been explored to treat metabolic syndrome by restoring the GM; however, concerns on accidentally transferring pathogenic microbes remain. As a safer alternative, fecal virome transplantation (FVT, sterile-filtrated feces) has the advantage over FMT in that mainly bacteriophages are transferred. FVT from lean male donors have shown promise in alleviating the metabolic effects of high-fat diet in a preclinical mouse study. However, FVT still carries the risk of eukaryotic viral infections. To address this, recently developed methods are applied for removing or inactivating eukaryotic viruses in the viral component of FVT. Modified FVTs are compared with unmodified FVT and saline in a diet-induced obesity model on male C57BL/6 N mice. Contrasted with obese control, mice administered a modified FVT (nearly depleted for eukaryotic viruses) exhibits enhanced blood glucose clearance but not weight loss. The unmodified FVT improves liver pathology and reduces the proportions of immune cells in the adipose tissue with a non-uniform response. GM analysis suggests that bacteriophage-mediated GM modulation influences outcomes. Optimizing these approaches could lead to the development of safe bacteriophage-based therapies targeting metabolic syndrome through GM restoration.

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Astragalus compound oral solution synergistically enhances health-promoting effect of metformin in type 2 diabetes mouse model

Cited by 2 publications

References 47 publications

Transfer of modified fecal viromes improve blood glucose regulation and alleviates symptoms of metabolic dysfunction-associated fatty liver disease in an obesity male mouse model

Transfer of modified fecal viromes improve blood glucose regulation and alleviates symptoms of metabolic dysfunction-associated fatty liver disease in an obesity male mouse model

Transfer of modified gut viromes improves symptoms associated with metabolic syndrome in obese male mice

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