To mechanistically validate the hypothesis that YCHD alleviates cholestasis through microbiota-driven FXR activation along the gut–liver axis, this study systematically investigates three interdependent questions: (1) whether gut microbiota is necessary for YCHD’s therapeutic efficacy; (2) how YCHD-remodeled microbiota reprograms BA metabolism to activate hepatic and intestinal FXR signaling; and (3) how microbiota-restructured FXR activation coordinates BA synthesis, transport, and barrier functions. The gene discussed is NR1H4; the disease is cholestasis.