Microarray analysis of FXR-regulated genes in murine small intestine.. Mus musculus

Obstruction of bile flow results in bacterial proliferation and mucosal injury in the small intestine that can lead to the translocation of bacteria across the epithelial barrier and systemic infection. These adverse effects of biliary obstruction can be inhibited by administration of bile acids. Here we show that the farnesoid X receptor (FXR), a nuclear receptor for bile acids, induces genes involved in enteroprotection and inhibits bacterial overgrowth and mucosal injury in ileum caused by bile duct ligation. Mice lacking FXR have increased ileal levels of bacteria and a compromised epithelial barrier. These findings reveal a central role for FXR in protecting the distal small intestine from bacterial invasion and suggest that FXR agonists may prevent epithelial deterioration and bacterial translocation in patients with impaired bile flow. In this report we have examined the role of FXR in the ileum. We demonstrate that it plays a crucial role in preventing bacterial overgrowth and maintaining the integrity of the intestinal epithelium Overall design: Mice were administered the FXR ligand GW4064 or vehicle for 14h. The ilium was removed and processed for array analysis. Each sample group was done in duplicate.

胆汁流受阻可引发小肠内细菌增殖与黏膜损伤，进而导致细菌跨越上皮屏障发生易位及全身感染。胆道梗阻的上述不良影响可通过给予胆汁酸得到抑制。
本研究证实，作为胆汁酸核受体的法尼醇X受体（farnesoid X receptor, FXR），能够诱导肠保护相关基因的表达，并可抑制胆管结扎所致的回肠细菌过度增殖与黏膜损伤。
缺失FXR的小鼠，其回肠内细菌水平升高，上皮屏障功能受损。
上述发现揭示了FXR在保护远端小肠免受细菌侵袭中的核心作用，并提示FXR激动剂或可预防胆汁流受损患者的上皮屏障破坏与细菌易位。
本研究针对FXR在回肠中的作用展开了探究，证实其在阻断细菌过度增殖、维持肠上皮完整性方面发挥关键作用。
总体实验设计：向小鼠给予FXR配体GW4064或溶剂对照，处理14小时后摘取回肠组织，用于阵列分析。每个样本组均设置双重复样本。