宫内生长受限（IUGR）仔猪肠道屏障功能受损，影响仔猪生长潜能。胆汁酸和核受体FXR在肠道屏障功能的调节中具有重要作用。前期研究发现，IUGR仔猪空肠胆汁酸代谢菌丰度降低、粪便鹅脱氧胆酸（CDCA）浓度以及空肠FXR基因表达量增加，但CDCA对IUGR仔猪肠上皮屏障的损伤作用以及FXR在其中的介导机制尚不明确。本项目从微生物-CDCA-肠道上皮屏障功能出发，以FXR为切入点，通过分析IUGR仔猪和正常出生重仔猪肠道CDCA浓度变化和胆汁酸代谢菌群特征，明确IUGR仔猪肠道微生物与CDCA的关联变化关系；建立仔猪CDCA灌喂模型，确定其对肠上皮屏障的损伤作用和FXR的影响；基于IUGR仔猪肠道FXR抑制和CDCA/FXR基因缺失/肠上皮细胞共培养模型，揭示FXR介导CDCA对IUGR仔猪肠上皮屏障损伤的分子机制。研究结果将为通过靶向调控FXR和CDCA，改善IUGR仔猪肠道健康提供理论依据。

Intrauterine growth restriction (IUGR) impair the gut barrier function in piglets, which often have negative consequences on their growth potential. Bile acids and farnesoid x receptor (FXR) play an important role in the regulation of intestinal barrier function. Our previous study found that IUGR decreased the abundance of bile acid metabolizing related bacteria in jejunum, increased the concentration of chenodesoxycholic acid (CDCA), and up-regulated gene expression of FXR in piglets, but the detrimental effects of CDCA on intestinal epithelial barrier of IUGR piglets and the mechanism of FXR acting as a mediator in this process have not been clarified. This program focuses on the CDCA-FXR-intestinal epithelial barrier function, taking IUGR piglets as the research object. Firstly, by investigating the changes of intestinal CDCA concentration and microbial bile acid metabolism in IUGR piglets, the relationship between intestinal microorganism and CDCA in IUGR piglets will be clarified; Secondly, the model of CDCA oral perfusion for normal birth weight piglets will be established to determine the damage effect of CDCA on intestinal epithelial barrier and the gene expression of FXR; Finally, the model of intestinal FXR inhibition in IUGR piglets and CDCA / FXR gene knockout / intestinal epithelial cell co-culture model will be further established to reveal the molecular mechanism of FXR-mediated damage of intestinal epithelial barrier by CDCA in IUGR piglets. These findings will provide the theoretical basis to improve the intestinal health of IUGR piglets by targeting and regulating the FXR and CDCA.