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

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Listed:
  • 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
    VitaKey Incorporation)

  • Janelle C. Arthur

    (The University of North Carolina at Chapel Hill
    The University of North Carolina at Chapel Hill
    The University of North Carolina at Chapel Hill)

  • Juliane Nguyen

    (University of North Carolina at Chapel Hill
    The University of North Carolina at Chapel Hill)

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.

Suggested Citation

  • Mairead K. Heavey & Anthony Hazelton & Yuyan Wang & Mitzy Garner & Aaron C. Anselmo & Janelle C. Arthur & Juliane Nguyen, 2024. "Targeted delivery of the probiotic Saccharomyces boulardii to the extracellular matrix enhances gut residence time and recovery in murine colitis," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48128-0
    DOI: 10.1038/s41467-024-48128-0
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    References listed on IDEAS

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    1. Zhenping Cao & Xinyue Wang & Yan Pang & Shanshan Cheng & Jinyao Liu, 2019. "Biointerfacial self-assembly generates lipid membrane coated bacteria for enhanced oral delivery and treatment," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    2. Fernando P. Canale & Camilla Basso & Gaia Antonini & Michela Perotti & Ning Li & Anna Sokolovska & Julia Neumann & Michael J. James & Stefania Geiger & Wenjie Jin & Jean-Philippe Theurillat & Kip A. W, 2021. "Metabolic modulation of tumours with engineered bacteria for immunotherapy," Nature, Nature, vol. 598(7882), pages 662-666, October.
    3. Elvin Koh & In Young Hwang & Hui Ling Lee & Ryan De Sotto & Jonathan Wei Jie Lee & Yung Seng Lee & John C. March & Matthew Wook Chang, 2022. "Engineering probiotics to inhibit Clostridioides difficile infection by dynamic regulation of intestinal metabolism," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
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