Targeted and quantitatively modeled biologic delivery via dual-functional probiotic yeast in inflammatory bowel disease.

Abstract

Probiotic-based therapies are an emerging class of therapeutic interventions that offer a promising strategy for managing chronic and inflammatory conditions. Here, we engineered a dual-functional probiotic yeast strain, Saccharomyces boulardii, designed to target inflammatory lesions within the gastrointestinal tract and locally deliver protein-based therapeutics. We employed advanced experimental and modeling techniques to characterize the engineered probiotic with preclinical therapeutic efficacy and pharmacokinetic validation in an inflammatory bowel disease (IBD) mouse model. Through these studies, we demonstrate that our engineered yeast enables efficient and localized delivery of biologics with prolonged gastrointestinal retention, driving restorative phenotypic shifts towards measurable improvements in disease outcome. Overall, this work establishes a robust framework for the development of engineered microbial therapeutics, representing an integrative strategy for treating chronic, inflammatory diseases through targeted, localized delivery of bioactive molecules.