Oral delivery of GLP-1 peptide using recombinant Lactobacillus gasseri for the treatment of type 2 diabetes mellitus
ABSTRACT Glucagon-like peptide-1 (GLP-1) is an effective therapeutic peptide for the treatment of type 2 diabetes mellitus (T2DM). Here, we constructed an effective probiotic-based oral GLP-1 delivery system by engineering the probiotic strain of Lactobacillus gasseri (LgsGPA) to secrete GLP-1 fusio...
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| Language: | English |
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American Society for Microbiology
2025-08-01
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| Series: | Microbiology Spectrum |
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| Online Access: | https://journals.asm.org/doi/10.1128/spectrum.02828-24 |
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| author | Zhiqiang Ke Qianqian Ma Xiaonan Ye Yan Jin Yanlin Wang Xinyuan Zhao Zhengding Su |
| author_facet | Zhiqiang Ke Qianqian Ma Xiaonan Ye Yan Jin Yanlin Wang Xinyuan Zhao Zhengding Su |
| author_sort | Zhiqiang Ke |
| collection | DOAJ |
| description | ABSTRACT Glucagon-like peptide-1 (GLP-1) is an effective therapeutic peptide for the treatment of type 2 diabetes mellitus (T2DM). Here, we constructed an effective probiotic-based oral GLP-1 delivery system by engineering the probiotic strain of Lactobacillus gasseri (LgsGPA) to secrete GLP-1 fusion peptide, which combines GLP-1 with protein transduction domain (PTD) and a serum albumin binding peptide (ABP), GLP-1-PTD-ABP (GPA). The supernatants of LgsGPA cultures significantly upregulated the expression of PDX-1 and stimulated insulin release in Min6 cells. Daily oral administration of LgsGPA in db/db mice significantly alleviated insulin resistance, hyperglycemia, and dyslipidemia. Simultaneously, the abundance of unclassified_f_Erysipelotrichaceae and Intestinimonas was significantly reduced in db/db mice, while the average abundance of Akkermansia increased in the SD rats. These findings demonstrate that the probiotic-based delivery system represents a versatile and effective strategy for the oral administration of therapeutic peptides. Collectively, our results highlight the potential of this probiotic-based approach as a promising therapeutic and preventive intervention for T2DM.IMPORTANCEIt is important to develop the oral delivery strategy for therapeutic peptides. Due to issues with patient adherence and the low oral bioavailability of current administration methods, researchers have been exploring oral delivery strategies for GLP-1 analogs for many years, including the use of advanced microbiome therapeutics (AMTs). AMTs offer the potential to use engineered microbes for innovative therapeutic applications, such as the oral delivery of GLP-1 analogs. Our approaches offer a general oral delivery strategy for therapeutic peptides. The probiotic-based approach represents a promising method for treating and preventing T2DM. |
| format | Article |
| id | doaj-art-044e70133ad84eb6b3760395395e4814 |
| institution | DOAJ |
| issn | 2165-0497 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | Microbiology Spectrum |
| spelling | doaj-art-044e70133ad84eb6b3760395395e48142025-08-20T02:56:20ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972025-08-0113810.1128/spectrum.02828-24Oral delivery of GLP-1 peptide using recombinant Lactobacillus gasseri for the treatment of type 2 diabetes mellitusZhiqiang Ke0Qianqian Ma1Xiaonan Ye2Yan Jin3Yanlin Wang4Xinyuan Zhao5Zhengding Su6Protein Engineering and Biopharmaceuticals science, Hubei University of Technology, Wuhan, ChinaProtein Engineering and Biopharmaceuticals science, Hubei University of Technology, Wuhan, ChinaProtein Engineering and Biopharmaceuticals science, Hubei University of Technology, Wuhan, ChinaProtein Engineering and Biopharmaceuticals science, Hubei University of Technology, Wuhan, ChinaProtein Engineering and Biopharmaceuticals science, Hubei University of Technology, Wuhan, ChinaNational Demonstration Center for Experimental General Medicine Education, School of Basic Medical Sciences, Hubei University of Science and Technology, Xianning, ChinaProtein Engineering and Biopharmaceuticals science, Hubei University of Technology, Wuhan, ChinaABSTRACT Glucagon-like peptide-1 (GLP-1) is an effective therapeutic peptide for the treatment of type 2 diabetes mellitus (T2DM). Here, we constructed an effective probiotic-based oral GLP-1 delivery system by engineering the probiotic strain of Lactobacillus gasseri (LgsGPA) to secrete GLP-1 fusion peptide, which combines GLP-1 with protein transduction domain (PTD) and a serum albumin binding peptide (ABP), GLP-1-PTD-ABP (GPA). The supernatants of LgsGPA cultures significantly upregulated the expression of PDX-1 and stimulated insulin release in Min6 cells. Daily oral administration of LgsGPA in db/db mice significantly alleviated insulin resistance, hyperglycemia, and dyslipidemia. Simultaneously, the abundance of unclassified_f_Erysipelotrichaceae and Intestinimonas was significantly reduced in db/db mice, while the average abundance of Akkermansia increased in the SD rats. These findings demonstrate that the probiotic-based delivery system represents a versatile and effective strategy for the oral administration of therapeutic peptides. Collectively, our results highlight the potential of this probiotic-based approach as a promising therapeutic and preventive intervention for T2DM.IMPORTANCEIt is important to develop the oral delivery strategy for therapeutic peptides. Due to issues with patient adherence and the low oral bioavailability of current administration methods, researchers have been exploring oral delivery strategies for GLP-1 analogs for many years, including the use of advanced microbiome therapeutics (AMTs). AMTs offer the potential to use engineered microbes for innovative therapeutic applications, such as the oral delivery of GLP-1 analogs. Our approaches offer a general oral delivery strategy for therapeutic peptides. The probiotic-based approach represents a promising method for treating and preventing T2DM.https://journals.asm.org/doi/10.1128/spectrum.02828-24glucagon-like peptide-1advanced microbiome deliveryprotein transduction domainserum albumin binding peptideoral deliveryGLP-1 analog |
| spellingShingle | Zhiqiang Ke Qianqian Ma Xiaonan Ye Yan Jin Yanlin Wang Xinyuan Zhao Zhengding Su Oral delivery of GLP-1 peptide using recombinant Lactobacillus gasseri for the treatment of type 2 diabetes mellitus Microbiology Spectrum glucagon-like peptide-1 advanced microbiome delivery protein transduction domain serum albumin binding peptide oral delivery GLP-1 analog |
| title | Oral delivery of GLP-1 peptide using recombinant Lactobacillus gasseri for the treatment of type 2 diabetes mellitus |
| title_full | Oral delivery of GLP-1 peptide using recombinant Lactobacillus gasseri for the treatment of type 2 diabetes mellitus |
| title_fullStr | Oral delivery of GLP-1 peptide using recombinant Lactobacillus gasseri for the treatment of type 2 diabetes mellitus |
| title_full_unstemmed | Oral delivery of GLP-1 peptide using recombinant Lactobacillus gasseri for the treatment of type 2 diabetes mellitus |
| title_short | Oral delivery of GLP-1 peptide using recombinant Lactobacillus gasseri for the treatment of type 2 diabetes mellitus |
| title_sort | oral delivery of glp 1 peptide using recombinant lactobacillus gasseri for the treatment of type 2 diabetes mellitus |
| topic | glucagon-like peptide-1 advanced microbiome delivery protein transduction domain serum albumin binding peptide oral delivery GLP-1 analog |
| url | https://journals.asm.org/doi/10.1128/spectrum.02828-24 |
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