Microbiota of MR1 deficient mice confer resistance against Clostridium difficile infection

by Ashley D. Smith, Elissa D. Foss, Irma Zhang, Jessica L. Hastie, Nicole P. Giordano, Lusine Gasparyan, Lam Phuc VinhNguyen, Alyxandria M. Schubert, Deepika Prasad, Hannah L. McMichael, Jinchun Sun, Richard D. Beger, Vahan Simonyan, Siobhán C. Cowley, Paul E. Carlson Jr

Clostridium difficile (Cd) infection (CDI) typically occurs after antibiotic usage perturbs the gut microbiota. Mucosa-associated invariant T cells (MAIT) are found in the gut and their development is dependent on Major histocompatibility complex-related protein 1 (MR1) and the host microbiome. Here we were interested in determining whether the absence of MR1 impacts resistance to CDI. To this end, wild-type (WT) and MR1^-/- mice were treated with antibiotics and then infected with Cd spores. Surprisingly, MR1^-/- mice exhibited resistance to Cd colonization. 16S rRNA gene sequencing of feces revealed inherent differences in microbial composition. This colonization resistance was transferred from MR1^-/- to WT mice via fecal microbiota transplantation, suggesting that MR1-dependent factors influence the microbiota, leading to CDI susceptibility.