胆道梗阻疾病常由肠道屏障功能受损所复杂化，加重了肝脏损伤。肠道屏障的治疗常被忽视。为了探究胆道梗阻后肠道胆汁酸缺乏介导的肠道屏障功能紊乱的机制，并确定潜在的治疗方案，我们主要使用了胆管结扎（BDL）小鼠模型模拟胆道梗阻，确定胆酸受体FXR在维持肠道屏障功能和干性细胞状态中的重要作用。通过对BDL和模拟手术小鼠crypt和肠上皮特异Fxr敲除（FxrΔIEC）和野生型小鼠crypt进行RNA测序分析和qRT-PCR，我们发现FXR可能通过调节CYP11A1的表达来维持肠道干性细胞状态。鉴于CYP11A1在糖皮质激素产生过程中的关键作用，我们还发现FXR激活可以通过ELISA促进肠道的皮质酮（CORT）合成。肠道器官培养显示，FXR激动剂或皮质酮可以增加crypt形成和器官培养的增长。进一步的动物实验显示，皮质酮灌胃治疗可以维持肠道屏障功能和干性细胞状态，降低LPS移位，减轻BDL小鼠的肝脏损伤。本研究有望为胆道梗阻后肠道并发症的预防和肝脏损伤的缓解提供新的理论依据。

Biliary obstruction diseases are often complicated by an impaired intestinal barrier, which aggravates liver injury. Treatment of the intestinal barrier is often neglected. To investigate the mechanism by which intestinal bile acid deficiency mediates intestinal barrier dysfunction after biliary obstruction and identify a potential therapeutic modality, we mainly used a bile duct ligation (BDL) mouse model to simulate biliary obstruction and determine the important role of the bile acid receptor FXR in maintaining intestinal barrier function and stemness. Through RNA-seq analysis of BDL and sham mouse crypts and qRT-PCR performed on intestinal epithelial-specific Fxr knockout (FxrΔIEC) and wild-type mouse crypts, we found that FXR might maintain intestinal stemness by regulating CYP11A1 expression. Given the key role of CYP11A1 during glucocorticoid production, we also found that FXR activation could promote intestinal corticosterone (CORT) synthesis by ELISA. Intestinal organoid culture showed that an FXR agonist or corticosterone increased crypt formation and organoid growth. Further animal experiments showed that corticosterone gavage treatment could maintain intestinal barrier function and stemness, decrease LPS translocation, and attenuate liver injury in BDL mice. Our study hopefully provides a new theoretical basis for the prevention of intestinal complications and alleviation of liver injury after biliary obstruction.