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Host immunity modulates the efficacy of microbiota transplantation for treatment of Clostridioides difficile infection

Author

Listed:
  • Eric R. Littmann

    (University of Chicago)

  • Jung-Jin Lee

    (Children’s Hospital of Philadelphia)

  • Joshua E. Denny

    (University of Pennsylvania)

  • Zahidul Alam

    (University of Pennsylvania)

  • Jeffrey R. Maslanka

    (University of Pennsylvania)

  • Isma Zarin

    (University of Pennsylvania)

  • Rina Matsuda

    (University of Pennsylvania School of Veterinary Medicine)

  • Rebecca A. Carter

    (Sloan-Kettering Institute, Memorial Sloan Kettering Cancer Center)

  • Bože Susac

    (Sloan-Kettering Institute, Memorial Sloan Kettering Cancer Center)

  • Miriam S. Saffern

    (Sloan-Kettering Institute, Memorial Sloan Kettering Cancer Center)

  • Bryton Fett

    (Children’s Hospital of Philadelphia)

  • Lisa M. Mattei

    (Children’s Hospital of Philadelphia)

  • Kyle Bittinger

    (Children’s Hospital of Philadelphia)

  • Michael C. Abt

    (University of Pennsylvania)

Abstract

Fecal microbiota transplantation (FMT) is a successful therapeutic strategy for treating recurrent Clostridioides difficile infection. Despite remarkable efficacy, implementation of FMT therapy is limited and the mechanism of action remains poorly understood. Here, we demonstrate a critical role for the immune system in supporting FMT using a murine C. difficile infection system. Following FMT, Rag1 heterozygote mice resolve C. difficile while littermate Rag1−/− mice fail to clear the infection. Targeted ablation of adaptive immune cell subsets reveal a necessary role for CD4+ Foxp3+ T-regulatory cells, but not B cells or CD8+ T cells, in FMT-mediated resolution of C. difficile infection. FMT non-responsive mice exhibit exacerbated inflammation, impaired engraftment of the FMT bacterial community and failed restoration of commensal bacteria-derived secondary bile acid metabolites in the large intestine. These data demonstrate that the host’s inflammatory immune status can limit the efficacy of microbiota-based therapeutics to treat C. difficile infection.

Suggested Citation

  • Eric R. Littmann & Jung-Jin Lee & Joshua E. Denny & Zahidul Alam & Jeffrey R. Maslanka & Isma Zarin & Rina Matsuda & Rebecca A. Carter & Bože Susac & Miriam S. Saffern & Bryton Fett & Lisa M. Mattei &, 2021. "Host immunity modulates the efficacy of microbiota transplantation for treatment of Clostridioides difficile infection," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-020-20793-x
    DOI: 10.1038/s41467-020-20793-x
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    Cited by:

    1. Laurence D. W. Luu & Abhimanu Pandey & Sudarshan Paramsothy & Chinh Ngo & Natalia Castaño-Rodríguez & Cheng Liu & Michael A. Kamm & Thomas J. Borody & Si Ming Man & Nadeem O. Kaakoush, 2024. "Profiling the colonic mucosal response to fecal microbiota transplantation identifies a role for GBP5 in colitis in humans and mice," Nature Communications, Nature, vol. 15(1), pages 1-13, December.

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