Engineered Probiotic Saccharomyces boulardii Produces Functional Insulin With Long-Acting Effect in Mice Model

Area of Science:

• Biotechnology
• Microbiology
• Metabolic Disorders

Background:

• Diabetes mellitus impacts over 500 million globally, with current insulin injections having limitations.
• Subcutaneous insulin delivery can impair natural glucose regulation and lead to poor patient compliance.
• Oral insulin delivery is desirable but faces challenges like gastrointestinal degradation and low absorption.

Purpose of the Study:

• To engineer Saccharomyces boulardii for the production and secretion of a functional insulin-Fc fusion protein.
• To establish a viable platform for oral insulin delivery using a probiotic yeast.

Main Methods:

• Engineered Saccharomyces boulardii using strong constitutive promoters (TDH3 and TEF1).
• Created a long-acting Insulin-Fc fusion protein (Ins/Fc).
• Validated expression and bioactivity in vitro and in vivo models.

Main Results:

• Achieved stable expression of the Ins/Fc fusion protein in engineered S. boulardii strains (FZ030 and FZ032).
• Demonstrated functional bioactivity of the secreted Ins/Fc protein in cell cultures.
• Confirmed bioactivity in a mouse model of diabetes.

Conclusions:

• Successfully engineered S. boulardii to produce functional insulin, marking a significant advancement.
• This probiotic yeast platform shows potential for developing effective oral insulin delivery systems.
• Represents a novel approach to overcome limitations of current diabetes therapies.