In patients with active IBD, fecal levels of conjugated (primary) BAs are significantly elevated, while levels of secondary BAs are markedly decreased.70 Secondary BAs exhibit higher affinity for TGR5 than primary BAs.71 Activation of the TGR5 receptor can modulate the phenotypic conversion of macrophages toward an M2-predominant anti-inflammatory phenotype, inhibiting the production of NF-κB-related pro-inflammatory cytokines.52 Therefore, the decrease in secondary BA levels may contribute to IBD susceptibility by affecting the anti-inflammatory pathway of TGR5. This evidence concerns the gene GPBAR1 and inflammatory bowel disease.