Targeted delivery of the probiotic Saccharomyces boulardii to the extracellular matrix enhances gut residence time and recovery in murine colitis

Mairead K. Heavey, Anthony Hazelton, Yuyan Wang, Mitzy Garner, Aaron C. Anselmo, Janelle C. Arthur () and Juliane Nguyen ()
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Mairead K. Heavey: University of North Carolina at Chapel Hill
Anthony Hazelton: University of North Carolina at Chapel Hill
Yuyan Wang: University of North Carolina at Chapel Hill
Mitzy Garner: University of North Carolina at Chapel Hill
Aaron C. Anselmo: University of North Carolina at Chapel Hill
Janelle C. Arthur: The University of North Carolina at Chapel Hill
Juliane Nguyen: University of North Carolina at Chapel Hill

Nature Communications, 2024, vol. 15, issue 1, 1-16

Abstract: Abstract Probiotic and engineered microbe-based therapeutics are an emerging class of pharmaceutical agents. They represent a promising strategy for treating various chronic and inflammatory conditions by interacting with the host immune system and/or delivering therapeutic molecules. Here, we engineered a targeted probiotic yeast platform wherein Saccharomyces boulardii is designed to bind to abundant extracellular matrix proteins found within inflammatory lesions of the gastrointestinal tract through tunable antibody surface display. This approach enabled an additional 24–48 h of probiotic gut residence time compared to controls and 100-fold increased probiotic concentrations within the colon in preclinical models of ulcerative colitis in female mice. As a result, pharmacodynamic parameters including colon length, colonic cytokine expression profiles, and histological inflammation scores were robustly improved and restored back to healthy levels. Overall, these studies highlight the potential for targeted microbial therapeutics as a potential oral dosage form for the treatment of inflammatory bowel diseases.

Date: 2024
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DOI: 10.1038/s41467-024-48128-0

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