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Rationally designed bacterial consortia to treat chronic immune-mediated colitis and restore intestinal homeostasis

Author

Listed:
  • Daniel Lelie

    (Gusto Global LLC)

  • Akihiko Oka

    (University of North Carolina at Chapel Hill
    Shimane University Faculty of Medicine)

  • Safiyh Taghavi

    (Gusto Global LLC)

  • Junji Umeno

    (University of North Carolina at Chapel Hill
    Kyushu University)

  • Ting-Jia Fan

    (Gusto Global LLC)

  • Katherine E. Merrell

    (Gusto Global LLC)

  • Sarah D. Watson

    (Gusto Global LLC)

  • Lisa Ouellette

    (Gusto Global LLC)

  • Bo Liu

    (University of North Carolina at Chapel Hill)

  • Muyiwa Awoniyi

    (University of North Carolina at Chapel Hill)

  • Yunjia Lai

    (University of North Carolina at Chapel Hill)

  • Liang Chi

    (University of North Carolina at Chapel Hill)

  • Kun Lu

    (University of North Carolina at Chapel Hill)

  • Christopher S. Henry

    (Gusto Global LLC)

  • R. Balfour Sartor

    (University of North Carolina at Chapel Hill)

Abstract

Environmental factors, mucosal permeability and defective immunoregulation drive overactive immunity to a subset of resident intestinal bacteria that mediate multiple inflammatory conditions. GUT-103 and GUT-108, live biotherapeutic products rationally designed to complement missing or underrepresented functions in the dysbiotic microbiome of IBD patients, address upstream targets, rather than targeting a single cytokine to block downstream inflammation responses. GUT-103, composed of 17 strains that synergistically provide protective and sustained engraftment in the IBD inflammatory environment, prevented and treated chronic immune-mediated colitis. Therapeutic application of GUT-108 reversed established colitis in a humanized chronic T cell-mediated mouse model. It decreased pathobionts while expanding resident protective bacteria; produced metabolites promoting mucosal healing and immunoregulatory responses; decreased inflammatory cytokines and Th-1 and Th-17 cells; and induced interleukin-10-producing colonic regulatory cells, and IL-10-independent homeostatic pathways. We propose GUT-108 for treating and preventing relapse for IBD and other inflammatory conditions characterized by unbalanced microbiota and mucosal permeability.

Suggested Citation

  • Daniel Lelie & Akihiko Oka & Safiyh Taghavi & Junji Umeno & Ting-Jia Fan & Katherine E. Merrell & Sarah D. Watson & Lisa Ouellette & Bo Liu & Muyiwa Awoniyi & Yunjia Lai & Liang Chi & Kun Lu & Christo, 2021. "Rationally designed bacterial consortia to treat chronic immune-mediated colitis and restore intestinal homeostasis," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-23460-x
    DOI: 10.1038/s41467-021-23460-x
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    Cited by:

    1. Rémi Le Guern & Teddy Grandjean & Sarah Stabler & Marvin Bauduin & Philippe Gosset & Éric Kipnis & Rodrigue Dessein, 2023. "Gut colonisation with multidrug-resistant Klebsiella pneumoniae worsens Pseudomonas aeruginosa lung infection," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    2. Matthias Bec & Sylvain Pouzet & Céline Cordier & Simon Barral & Vittore Scolari & Benoit Sorre & Alvaro Banderas & Pascal Hersen, 2024. "Optogenetic spatial patterning of cooperation in yeast populations," Nature Communications, Nature, vol. 15(1), pages 1-14, December.

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