LAUSR

Chenodeoxycholic acid (CDCA), a primary bile acid, has been demonstrated to play important roles as signaling molecule in various physiology functions. However, the role of CDCA in regulating intestinal barrier function remains largely unknown. This study aimed to investigate the effects of CDCA on LPS-impaired intestinal epithelial barrier function and explore the underlying mechanisms. In IPEC-J2 cells, CDCA reversed LPS-induced increase in TEER and decrease in tight junction proteins expression. In addition, we found that FXR but not TGR5 was responsible for CDCA-improved epithelial barrier impairment induced by LPS. Furthermore, CDCA blocked LPS-induced activation of MLCK pathway in a FXR-dependent manner and elicited similar effects to MLCK inhibition. In mice, CDCA supplementation restored LPS-induced elevation of intestinal permeability and MLCK expression and reduction of tight junction proteins expression, thus alleviating LPS-induced intestinal barrier impairment. In conclusion, CDCA protected against the LPS-induced impairment of intestinal epithelial barrier function via FXR-MLCK pathway.