To investigate whether IFN-γ play an important role in the protection against CDI, 10 μg recombinant IFN-γ was intraperitoneally injected into mice at 2 h p.i. and 24 h p.i. We found that IFN-γ treatment greatly improved C. difficile-induced body weight loss (Supplementary Fig. 4A), reduced the DAI (Supplementary Fig. 4B), and alleviated the intestinal epithelium damage with longer colon length and lower histological score (Supplementary Fig. 4C–E), as well as the T.mu treatment. Here, IFNG is linked to clostridium difficile infection.