Bile acids reversible effects on small intestinal permeability

Abstract

To define the action of deconjugated bile acids on the small intestinal permeability in an in vitro system, we investigated the effects of chenodeoxycholic acid and ursodeoxycholic acid on the rate of transmural flux of lactulose in jejunal and ileal mucosa of rabbits, stripped of their muscle layers and mounted in Ussing chambers. In a series of experiments, tissue samples from small intestinal segments either exposed to bile acids or not also were examined by scanning and transmission electron microscopy to study the integrity of the tight junctions. Results show that chenodeoxycholate, starting at the concentration of 0.1 mM, enhanced in a dose-related manner the transepithelial flux of lactulose in the ileum. Both chenodeoxycholate (0.5 mM) and ursodeoxycholate (0.5 mM) significantly increased mucosal permeability to lactulose in jejunum and ileum; the effect of chenodeoxycholate was also shown to be reversible, as it completely disappeared within 40 min after its withdrawal and it did not result in permanent changes of epithelial transport function. Finally, the tight junctions appeared loosened by the addition of 1 mM chenodeoxycholate, suggesting that this is the major site of the transient bile acid increase of small intestinal permeability to compounds such as lactulose, having a molecular radius wider than 0.5 nm.

Evaluation of Mucosal Damage and Recovery in the Gastrointestinal Tract of Rats by a Penetration Enhancer

“…However, the recovery times are highly dependent upon the type of model used in the study. For example, when the rabbit jejunum was treated with 0.5 mM chenodeoxycholate for 25 min in an in vitro system, mucosal permeability to lactulose returned to the normal value after 40 min (52). Similarly, when the guinea pig ileum was exposed to 0.06% Triton-X 100 (0.75 mM) for 5 min in an in vitro model, it took one hour for the tissue to seal the defect, when observed under a light microscope (53).…”

“…Examples of these materials include spices such as pepper (23,24) and garlic (25,26), hydrolytic food products and fatty meals (27,28), and alcoholic beverages (29,30). Drugs like NSAIDs (31,32), common laxatives (33)(34)(35) which are used commonly on a recurring basis and chenodeoxycholic acid (36)(37)(38) which has been used therapeutically since the early 1970's for the dissolution of gallstones for up to 2 years, have been shown to cause reversible damage in the gastrointestinal mucosa (39).…”

Abnormal Intestinal Permeability in Primary Biliary Cirrhosis

“…Our patients were not taking ASA, NSAIDs, or alcohol, all known to affect permeability, at the time the test was performed [28,29]. Bile acids have been shown to reversibly increase jejunal and ileal permeability in rabbits, however, this has not been studied in humans [30]. If UDCA had a major effect on human intestinal permeability, a greater proportion of the PBC cohort would likely have had abnormal results given that they were all on therapy.…”

Studies of the small bowel surface by scanning electron microscopy in infants with persistent diarrhea

“…Since high counts of aerobic and anaerobic bacteria have been found in the jejunal secretion of infants with persistent diarrhea, it has been suggested that bacterial proliferation could be responsible for the perpetuation of diarrhea and nutrient malabsorption (23). In fact, bacterial overgrowth in the small bowel lumen may be responsible for several functional and morphological abnormalities such as deconjugation and 7 a dehydroxylation of primary bile salts (24), sodium and water secretion (25), glucose malabsorption (26) and rupture of the intestinal permeability barrier favoring the penetration of intact macromolecules (27), and thus potentially leading to food allergy. Colitis was observed in 10 patients but an enteroinvasive microorganism was isolated from only 2 of them, and therefore food allergy might account for the remaining cases of colitis observed in our series.…”