Despite the fact that the role of Reg3 exerting prebiotic or opposite actions is largely unknown, growing evidence has demonstrated that Reg3 hyperexpression during acute IBD inflammation depletes intestinal Enterococcus faecium (a beneficial commensal symbiont) and thereafter blocks Nod2‐mediated anti‐inflammatory signaling (He and Zhou 2023; Jang et al. 2023). This evidence concerns the gene NOD2 and inflammatory bowel disease.