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

Littmann, Eric R., Lee, Jung-Jin, Denny, Joshua E., Alam, Zahidul, Maslanka, Jeffrey R., Zarin, Isma, Matsuda, Rina, Carter, Rebecca A., Susac, Bože, Saffern, Miriam S., Fett, Bryton, Mattei, Lisa M., Bittinger, Kyle, Abt, Michael C.·2021·Nature Communications
DOI 10.1038/s41467-020-20793-xPMC PMC7854624
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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.

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Metadata

Authors
Littmann, E. R., Lee, J.-J., Denny, J. E., Alam, Z., Maslanka, J. R., Zarin, I., Matsuda, R., Carter, R. A., Susac, B., Saffern, M. S., Fett, B., Mattei, L. M., Bittinger, K., & Abt, M. C.
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2021-02-02
Volume
12
Issue
1
ISSN
2041-1723
DOI
10.1038/s41467-020-20793-x
PMC
PMC7854624
Cited by
88
References
23
Language
en
Licence
Funders
U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (AI125786)

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