Hypoglycemic effect of C. butyricum-pMTL007-GLP-1 engineered probiotics on type 2 diabetes mellitus
Diabetes mellitus (DM) is a complex metabolic disease characterized by hyperglycemia. Recently, the incidence of diabetes has increased exponentially, and it is estimated to become the seventh leading cause of global mortality by 2030. Glucagon-like peptide-1 (GLP-1), a hormone derived from the inte...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2025-12-01
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| Series: | Gut Microbes |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/19490976.2024.2447814 |
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| author | Dexi Zhou Shengjie Li Gang Hu Yufan Wang Zhanghua Qi Xuan Xu Jing Wei Qiong Liu Tingtao Chen |
| author_facet | Dexi Zhou Shengjie Li Gang Hu Yufan Wang Zhanghua Qi Xuan Xu Jing Wei Qiong Liu Tingtao Chen |
| author_sort | Dexi Zhou |
| collection | DOAJ |
| description | Diabetes mellitus (DM) is a complex metabolic disease characterized by hyperglycemia. Recently, the incidence of diabetes has increased exponentially, and it is estimated to become the seventh leading cause of global mortality by 2030. Glucagon-like peptide-1 (GLP-1), a hormone derived from the intestine, has been demonstrated to exert remarkable hypoglycemic effects. However, its limitation lies in its short plasma half-life, necessitating the continuous intravenous injection of GLP-1 drugs to achieve efficacy. Here, we engineered Clostridium butyricum to continuously express and deliver GLP-1 (denoted as Cb-GLP-1), and assessed its therapeutic efficacy in type 2 diabetes mellitus (T2DM) mice. We demonstrated that administration of Cb-GLP-1 effectively lowered blood glucose levels, regulated dyslipidemia, and ameliorated hepatic impairment in T2DM mice. Furthermore, Cb-GLP-1 treatment facilitated insulin secretion by retarding islet cell apoptosis and activating the glucagon-like peptide 1 receptor/adenylate cyclase/protein kinase A (GLP-1 R/AC/PKA) signaling pathway. Gut microbiota analysis revealed that Cb-GLP-1 restored gut homeostasis disrupted in T2DM mice, as indicated by the decreased abundance of Lactobacillus and Providencia genera in response to Cb-GLP-1 treatment. Collectively, the intestinal microbiota regulation and hypoglycemic effect of the engineered strain Cb-GLP-1 presents a promising approach for diabetes management. |
| format | Article |
| id | doaj-art-9258ca82cafe4717a0bc7352c5aa9b2f |
| institution | DOAJ |
| issn | 1949-0976 1949-0984 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Gut Microbes |
| spelling | doaj-art-9258ca82cafe4717a0bc7352c5aa9b2f2025-08-20T02:56:29ZengTaylor & Francis GroupGut Microbes1949-09761949-09842025-12-0117110.1080/19490976.2024.2447814Hypoglycemic effect of C. butyricum-pMTL007-GLP-1 engineered probiotics on type 2 diabetes mellitusDexi Zhou0Shengjie Li1Gang Hu2Yufan Wang3Zhanghua Qi4Xuan Xu5Jing Wei6Qiong Liu7Tingtao Chen8School of Pharmacy, Jiangxi Medical College, Nanchang University, Nanchang, ChinaNational Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Jiangxi Medical College, Nanchang University, Nanchang, ChinaNational Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Jiangxi Medical College, Nanchang University, Nanchang, ChinaNational Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Jiangxi Medical College, Nanchang University, Nanchang, ChinaNational Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Jiangxi Medical College, Nanchang University, Nanchang, ChinaNational Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Jiangxi Medical College, Nanchang University, Nanchang, ChinaNational Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Jiangxi Medical College, Nanchang University, Nanchang, ChinaDepartment of Medical Microbiology, School of Medicine, Jiangxi Medical College, Nanchang University, Nanchang, ChinaSchool of Pharmacy, Jiangxi Medical College, Nanchang University, Nanchang, ChinaDiabetes mellitus (DM) is a complex metabolic disease characterized by hyperglycemia. Recently, the incidence of diabetes has increased exponentially, and it is estimated to become the seventh leading cause of global mortality by 2030. Glucagon-like peptide-1 (GLP-1), a hormone derived from the intestine, has been demonstrated to exert remarkable hypoglycemic effects. However, its limitation lies in its short plasma half-life, necessitating the continuous intravenous injection of GLP-1 drugs to achieve efficacy. Here, we engineered Clostridium butyricum to continuously express and deliver GLP-1 (denoted as Cb-GLP-1), and assessed its therapeutic efficacy in type 2 diabetes mellitus (T2DM) mice. We demonstrated that administration of Cb-GLP-1 effectively lowered blood glucose levels, regulated dyslipidemia, and ameliorated hepatic impairment in T2DM mice. Furthermore, Cb-GLP-1 treatment facilitated insulin secretion by retarding islet cell apoptosis and activating the glucagon-like peptide 1 receptor/adenylate cyclase/protein kinase A (GLP-1 R/AC/PKA) signaling pathway. Gut microbiota analysis revealed that Cb-GLP-1 restored gut homeostasis disrupted in T2DM mice, as indicated by the decreased abundance of Lactobacillus and Providencia genera in response to Cb-GLP-1 treatment. Collectively, the intestinal microbiota regulation and hypoglycemic effect of the engineered strain Cb-GLP-1 presents a promising approach for diabetes management.https://www.tandfonline.com/doi/10.1080/19490976.2024.2447814Type 2 diabetes mellitusClostridium butyricumGLP-1engineering probioticsinsulin secretiongut microbiota |
| spellingShingle | Dexi Zhou Shengjie Li Gang Hu Yufan Wang Zhanghua Qi Xuan Xu Jing Wei Qiong Liu Tingtao Chen Hypoglycemic effect of C. butyricum-pMTL007-GLP-1 engineered probiotics on type 2 diabetes mellitus Gut Microbes Type 2 diabetes mellitus Clostridium butyricum GLP-1 engineering probiotics insulin secretion gut microbiota |
| title | Hypoglycemic effect of C. butyricum-pMTL007-GLP-1 engineered probiotics on type 2 diabetes mellitus |
| title_full | Hypoglycemic effect of C. butyricum-pMTL007-GLP-1 engineered probiotics on type 2 diabetes mellitus |
| title_fullStr | Hypoglycemic effect of C. butyricum-pMTL007-GLP-1 engineered probiotics on type 2 diabetes mellitus |
| title_full_unstemmed | Hypoglycemic effect of C. butyricum-pMTL007-GLP-1 engineered probiotics on type 2 diabetes mellitus |
| title_short | Hypoglycemic effect of C. butyricum-pMTL007-GLP-1 engineered probiotics on type 2 diabetes mellitus |
| title_sort | hypoglycemic effect of c butyricum pmtl007 glp 1 engineered probiotics on type 2 diabetes mellitus |
| topic | Type 2 diabetes mellitus Clostridium butyricum GLP-1 engineering probiotics insulin secretion gut microbiota |
| url | https://www.tandfonline.com/doi/10.1080/19490976.2024.2447814 |
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