In light of a recent RNA-sequencing analysis showing that up-regulation of CH25H in patients with active IBD, while lacking evidence supporting a role of CH25H in intestinal homeostasis and IBD pathogenesis, we have performed in-depth analyses here, using animal models, to reveal how CH25H is acting as a critical regulator of the STATS/IL-6 signaling cascade in intestinal cells. Here, IL6 is linked to inflammatory bowel disease.