Background: Intestinal barrier integrity may be disrupted in many conditions allowing for bacterial invasion and ensuing systemic illness. We investigated the efficacy and mechanism of bile salts in protecting the intestinal mucosa integrity after injury through stimulation of cell proliferation and an increased resistance to apoptosis. Methods: Over 7 days, wild-type C57Bl/6J and Nr1h4tm1Gonz/J (farnesoid X receptor [FXR] knockout) male mice received either liquid rodent chow alone (for control animals) or with added 50 mg/kg per day of taurodeoxycholic acid (TDCA; for experimental animals). On day 6, all mice received 10 mL/kg of lipopolysaccharide intraperitoneally. On day 7, small intestines were harvested. After immunohistochemistry with hematoxylin and eosin, activated caspase-3, and 5-bromo2′-deoxy-uridine (BrdU), mean proliferating and apoptotic cells were determined with light microscopy. In vitro, FXR proteins were immunoblotted from cultured cells after exposure to TDCA. FXR expression was then inhibited in the presence and absence of TDCA. Intestinal epithelial proliferation along with c-Myc and FXR protein expressions were determined. Results: C57Bl/6J mice exhibited significant mucosal enterocyte proliferation and decreased mucosal enterocyte apoptosis when provided with supplemental TDCA in their diet. Inhibition of FXR, both in vivo and in vitro, prevented the bile salt-induced enterocyte proliferation and resistance to apoptosis. TDCA exposure stimulated nuclear translocation of FXR resulting in increased expression of c-Myc. Conclusion: A diet supplemented with bile salts, especially in patients who have decreased luminal bile salt, may prove beneficial and therapeutic in critical illness where intestinal injury is part of the spectrum.
ASJC Scopus subject areas