Obeticholic acid attenuates the intestinal barrier disruption in a rat model of short bowel syndrome.
Short bowel syndrome (SBS) features nutrients malabsorption and impaired intestinal barrier. Patients with SBS are prone to sepsis, intestinal flora dysbiosis and intestinal failure associated liver disease (IFALD). Protecting intestinal barrier and preventing complications are potential strategies for SBS treatment. This study aims to investigate the effects of farnesoid X receptor (FXR) agonist, obeticholic acid (OCA), have on intestinal barrier and ecological environment in SBS. Through testing the small intestine and serum samples of patients with SBS, impaired intestinal barrier was verified. The intestinal expressions of FXR-related molecules were decreased in SBS patients. Then, OCA was used to further dissect the potential role of the FXR in a rat model of SBS. OCA mitigated the damaged intestinal barrier and increased proinflammatory factors in SBS rats. The regulatory role of OCA on composition and function of gut microbiota in SBS rats was also observed through 16S rDNA sequencing. In vitro, OCA incubation of LPS-pretreated Caco-2 cells activated FXR-related molecules, increased expressions of tight junction proteins, ameliorated apoptosis and inhibited proinflammatory factors. In conclusion, OCA supplementation could effectively ameliorate the intestinal barrier disruption and inhibit overexpression of proinflammatory factors in a rat model of SBS and LPS-pretreated Caco-2 cells.