In summary, treatment of the Mdr2-/- mouse model of sclerosing cholangitis with the non-steroidal FXR agonist cilofexor improved histological features of sclerosing cholangitis, cholestasis and hepatic fibrosis, indicating that pharmacological stimulation of intestinal FXR-mediated gut-liver signaling via FGF15 (thereby reducing BA synthesis) may be sufficient to attenuate cholestatic liver injury in this mouse model. The gene discussed is NR1H4; the disease is cholestasis.