MIF Deficiency Modulates Gut Microbiota Composition and Promotes Colitis-Associated Colorectal Cancer in a Murine Model

Intestinal dysbiosis is a hallmark of both inflammatory bowel conditions and colorectal cancer, yet the mechanisms by which inflammatory mediators alter microbial communities and may contribute to tumor development remain poorly understood. Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine involved in innate immunity and the progression of inflammatory and neoplastic disorders. In this study, sequencing of the microbial 16S rRNA gene was performed to characterize the fecal microbiota profiles of wild-type (WT) and MIF-knockout (MIF-KO) BALB/c mice subjected to AOM/DSS-induced colitis-associated colorectal cancer (CAC). CAC induction resulted in marked microbial shifts, including increases in Muribaculaceae and Bacteroidota, in both WT and MIF-KO mice. Notably, MIF-KO CAC mice developed more severe disease compared with WT CAC mice. Furthermore, FMT experiments revealed that the fecal microbiota from MIF-KO donors was associated with increased tumor burden in WT recipients under CAC-inducing conditions compared with that in recipients colonized with WT-derived microbiota. Together, these findings suggest that MIF deficiency is associated with gut microbiota remodeling during CAC and support a potential relationship between the MIF-dependent host context, microbial composition and colorectal cancer severity.