We found that PGRN loss resulted in decreased protein expression levels of Occludin and ZO-1 in CDI, which are essential for maintaining epithelial junctional integrity.37 Therefore, PGRN plays a protective role in CDI by regulating intestinal barrier function and maintaining intestinal homeostasis, rather than by dampening C. difficile proliferation or toxin release in the cecal contents, which is similar with the beneficial roles of IL-25 or IL-33 in CDI.14,16. Here, IL33 is linked to clostridium difficile infection.