Engineered Microorganisms as GLP-1-Oriented Living Therapeutics for Diabetes and Obesity: Mechanisms and Translational Challenges
- 1Koltzov Institute of Developmental Biology of the Russian Academy of Sciences, 119334 Moscow, Russia
Abstract
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are established treatments for obesity and type 2 diabetes mellitus, but gastrointestinal barriers constrain oral delivery of peptide therapeutics. Genetically engineered microorganisms have been investigated as intestinal sources of GLP-1-related therapeutic molecules. These platforms produce GLP-1 or GLP-1-derived peptides, express modified GLP-1RAs or fusion proteins, or release effectors that stimulate endogenous GLP-1 secretion. Preclinical studies have reported improvements in glycemic measures and, in some models, reductions in body weight or weight gain. However, recombinant product expression and treatment-associated effects are more consistently demonstrated than exposure to intact biologically active products in vivo, receptor or pathway dependence, and the contribution of the engineered construct relative to the microbial chassis. Proteolysis, mucus interactions, restricted epithelial permeability, and receptor localization constrain access to intestinal and systemic targets. This review critically evaluates the preclinical evidence for GLP-1-oriented engineered microorganisms, with emphasis on intestinal target accessibility, local and systemic mechanisms, microbial chassis and genetic design, and the safety, manufacturing, and regulatory requirements for clinical translation.
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BibTeX
@article{lee2026engineered,
title = {{Engineered Microorganisms as GLP-1-Oriented Living Therapeutics for Diabetes and Obesity: Mechanisms and Translational Challenges}},
author = {Arthur A. Lee and Victoria A. Khotina and Olesya O. Klychkova and Vitalia S. Novikova and Dmitry A. Kashirskikh and Vagif A. Gasanov},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = nov,
doi = {10.3390/ijms27219977},
url = {https://www.mdpi.com/1422-0067/27/21/9977},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Engineered Microorganisms as GLP-1-Oriented Living Therapeutics for Diabetes and Obesity: Mechanisms and Translational Challenges
AU - Arthur A. Lee
AU - Victoria A. Khotina
AU - Olesya O. Klychkova
AU - Vitalia S. Novikova
AU - Dmitry A. Kashirskikh
AU - Vagif A. Gasanov
PY - 2026
DA - 2026/11/07
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219977
UR - https://www.mdpi.com/1422-0067/27/21/9977
AB - Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are established treatments for obesity and type 2 diabetes mellitus, but gastrointestinal barriers constrain oral delivery of peptide therapeutics. Genetically engineered microorganisms have been investigated as intestinal sources of GLP-1-related therapeutic molecules. These platforms produce GLP-1 or GLP-1-derived peptides, express modified GLP-1RAs or fusion proteins, or release effectors that stimulate endogenous GLP-1 secretion. Preclinical studies have reported improvements in glycemic measures and, in some models, reductions in body weight or weight gain. However, recombinant product expression and treatment-associated effects are more consistently demonstrated than exposure to intact biologically active products in vivo, receptor or pathway dependence, and the contribution of the engineered construct relative to the microbial chassis. Proteolysis, mucus interactions, restricted epithelial permeability, and receptor localization constrain access to intestinal and systemic targets. This review critically evaluates the preclinical evidence for GLP-1-oriented engineered microorganisms, with emphasis on intestinal target accessibility, local and systemic mechanisms, microbial chassis and genetic design, and the safety, manufacturing, and regulatory requirements for clinical translation.
SN - 1422-0067
ER -