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下一代益生菌-pMG36e-GLP-1对2型糖尿病肠道-胰腺-肝脏轴的改善作用

Improvement effect of a next-generation probiotic -pMG36e-GLP-1 on type 2 diabetes mellitus the gut-pancreas-liver axis.

作者信息

Hu Hong, Luo Jie, Liu Ying, Li Hongyu, Jin Rui, Li Shengjie, Wei Jing, Wei Hong, Chen Tingtao

机构信息

National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Nanchang University, Nanchang 330031, P. R. China.

School of Public Health and Key Laboratory of Preventive Medicine, Nanchang University, Nanchang 330031, P. R. China.

出版信息

Food Funct. 2023 Apr 3;14(7):3179-3195. doi: 10.1039/d3fo00044c.

Abstract

Next-generation probiotics (NGPs) are currently being investigated as therapeutic agents that impact the gut microbiota and disease development. Glucagon-like peptide-1 (GLP-1) shows an excellent therapeutic effect on diabetes, but has an extremely short half-life . Here, we constructed a novel and diabetes-specific NGP, the genetically engineered strain ()-pMG36e-GLP-1, and evaluated its ameliorative effect on type 2 diabetes mellitus (T2DM) in artificially induced mice and transgenic mice. , -pMG36e-GLP-1 showed good genetic stability and probiotic characteristics. In the high-fat diet combined with streptozotocin (HFD/STZ)-induced T2DM mice, -pMG36e-GLP-1 relieved the diabetic symptoms, regulated the intestinal microbiota, and reduced the inflammatory reaction in the pancreatic tissue. Meanwhile, the apoptosis of pancreatic islet cells was inhibited, while islet tissue morphology repairs, islet β-cell proliferation, and insulin secretion were all promoted by -pMG36e-GLP-1. Furthermore, a similar effect of the engineered strain on diabetic symptoms and the pancreas was observed in / mice, and the metabolism of lipids in the liver was regulated. Together, the findings of this study confirmed the anti-hyperglycemic effect of the engineered strain -pMG36e-GLP-1, providing a promising approach for T2DM treatment.

摘要

下一代益生菌(NGPs)目前正在作为影响肠道微生物群和疾病发展的治疗剂进行研究。胰高血糖素样肽-1(GLP-1)对糖尿病显示出优异的治疗效果,但半衰期极短。在此,我们构建了一种新型的、针对糖尿病的NGP,即基因工程菌株()-pMG36e-GLP-1,并评估了其对人工诱导小鼠和转基因小鼠2型糖尿病(T2DM)的改善作用。-pMG36e-GLP-1表现出良好的遗传稳定性和益生菌特性。在高脂饮食联合链脲佐菌素(HFD/STZ)诱导的T2DM小鼠中,-pMG36e-GLP-1缓解了糖尿病症状,调节了肠道微生物群,并减轻了胰腺组织中的炎症反应。同时,-pMG36e-GLP-1抑制了胰岛细胞的凋亡,促进了胰岛组织形态修复、胰岛β细胞增殖和胰岛素分泌。此外,在/小鼠中观察到该工程菌株对糖尿病症状和胰腺有类似作用,并且调节了肝脏中的脂质代谢。总之,本研究结果证实了工程菌株-pMG36e-GLP-1的降血糖作用,为T2DM治疗提供了一种有前景的方法。

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