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

   

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.
Article Title:	Host immunity modulates the efficacy of microbiota transplantation for treatment of Clostridioides difficile infection
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. © 2021, The Author(s).
Keywords:	bacteria (microorganisms); murinae; clostridium difficile; microbiota
Journal Title:	Nature Communications
Volume:	12
ISSN:	2041-1723
Publisher:	Nature Publishing Group
Date Published:	2021-02-02
Start Page:	755
Language:	English
DOI:	10.1038/s41467-020-20793-x
PUBMED:	33531483
PROVIDER:	scopus
PMCID:	PMC7854624
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85100353589&doi=10.1038%2fs41467-020-20793-x&partnerID=40&md5=228116c7ef33a0085b520499d19d0d5d
Notes:	Article -- Export Date: 1 March 2021 -- Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/177493