EFFECTS OF ORALLY ADMINISTERED ENGINEERED E. COLI EXPRESSING M-GLP-1 ON BODY WEIGHT IN A RAT MODEL OF TYPE 2 DIABETES

Introduction: Type 2 diabetes mellitus involves insulin resistance, β-cell dysfunction, and impaired metabolic homeostasis. GLP-1 receptor agonists improve glycemic control but generally require parenteral administration, while oral peptide delivery is limited by degradation and low bioavailability. Engineered microorganisms may provide an alternative platform for oral administration of peptide-expressing bacterial preparations. We evaluated orally administered E. coli engineered to express the recombinant GLP-1 variant M-GLP-1 in a rat model of type 2 diabetes.

Methods: M-GLP-1, generated by adding an N-terminal methionine to GLP-1(7–37), was expressed in E. coli BL21(DE3). Expression was induced with 200 µM IPTG. Cells were harvested, washed, lyophilized, and resuspended before administration. Male Wistar rats (n=50; 10/group; 7 weeks old) with high-fat diet/streptozotocin-induced type 2 diabetes were assigned to vehicle control, empty-vector E. coli control, or E. coli-M-GLP-1 at 1×, 2×, or 3× the therapeutic dose (1× = 2.8×10⁵ cells/animal). Preparations were administered by oral gavage twice weekly for 5 weeks. The study was approved by the Local Ethics Committee of Privolzhsky Research Medical University (Protocol No. 06, 29 April 2022).

Results: Body weight was comparable among groups before and after diabetes induction. During treatment, E. coli-M-GLP-1-treated rats showed greater body-weight gain than vehicle and empty-vector controls, with trajectories diverging from day 35. By day 56, mean body weight was approximately 299–301 g in the E. coli-M-GLP-1 groups versus 283–284 g in controls.

Conclusions: Oral E. coli-M-GLP-1 administration altered body-weight trajectories compared with vehicle and empty-vector controls in rats with experimental type 2 diabetes. These data do not establish GLP-1-mediated biological activity or confirm peptide delivery. Further studies are required to determine the metabolic significance and mechanism of the observed effect.