The Intricate Link among Gut “Immunological Niche,” Microbiota, and Xenobiotics in Intestinal Pathology

Figure 2

The role of rifaximin in modulating gut inflammation via the PXR/NF-κB pathway. Rifaximin is an effective agonist of the nuclear receptor PXR. PXR, greatly expressed in liver and intestinal mucosa, acts as a driver of detoxification processes and contributes to intestinal cell survival during exposure to several xenobiotics. After being activated by its ligands, PXR translocates into the nucleus where it binds its receptor and then regulates DNA transcription. The anti-inflammatory effects of rifaximin may not only be linked to the reduction of ileal bacteria load but it may also have an indirect action on inflammation. In fact, rifaximin, being an effective agonist of PXR, may regulate the inflammatory process. In particular, rifaximin, activating PXR, can inhibit NF-κB activity and the consequent transcription of several proinflammatory cytokines, such as TNF-alpha and IL-1β. The activation of PXR then upregulates p38 MAP kinase signal cascade via GADD45β upregulation. All these mechanisms are linked to the prevention of tissue damage and to favor gut mucosal healing.