Mounting evidence suggests gut microbiota modulate MHC class I/II gene expression in intestinal tissues (El Aidy et al., 2012; Koyama et al., 2019; Tuganbaev et al., 2020), positioning MHC-driven antigen presentation and immune cell activation as pivotal mechanisms in microbiota-mediated CDI defence. The gene discussed is HLA-C; the disease is clostridium difficile infection.