Our findings suggest that S100B induces NFκB activity during CDI, likely upregulating genes promoted by this transcription factor: IL-1α, IL-1β, IL-6, TNF-α, iNOS, CCL2, CCL3, CCR2, and CCR7. IL-22, which is secreted mainly by innate lymphoid cells type 3 (ILCs3) (Fachi et al., 2020), has been shown to play an important protective role in promoting epithelial regeneration and regulating intestinal microbiota during CDI (Fachi et al., 2020; Nagao-Kitamoto et al., 2020). Here, S100B is linked to clostridium difficile infection.