| First Author | Littmann ER | Year | 2021 |
| Journal | Nat Commun | Volume | 12 |
| Issue | 1 | Pages | 755 |
| PubMed ID | 33531483 | Mgi Jnum | J:303988 |
| Mgi Id | MGI:6514953 | Doi | 10.1038/s41467-020-20793-x |
| Citation | Littmann ER, et al. (2021) Host immunity modulates the efficacy of microbiota transplantation for treatment of Clostridioides difficile infection. Nat Commun 12(1):755 |
| abstractText | 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. |
