deoxycholic-acid and Ileitis

The small intestine plays a central role in gut immunity, and enhanced lymphocyte migration is involved in the pathophysiology of various enteropathy. Bile acid (BA) is closely related to lipid metabolism and gut microbiota and essential for gut homeostasis. However, the effects of BA on gut immunity have not been studied in detail, especially on the small intestine and lymphocyte migration. Therefore, we aimed to investigate the effect of BA on small intestinal lymphocyte microcirculation.. The effect of deoxycholic acid (DCA), taurocholic acid (tCA), or cholic acid (CA) on the indomethacin (IND)-induced small intestinal enteropathy in mice was investigated. Lymphocyte movements were evaluated after exposure to BA using intravital microscopy. The effects of BA on surface expression of adhesion molecules on the vascular endothelium and lymphocytes through BA receptors were examined in vitro.. IND-induced small intestinal enteropathy was histologically aggravated by DCA treatment alone. The expression of adhesion molecules ICAM-1 and VCAM-1 was significantly enhanced by DCA. Exposure to DCA increased lymphocyte adhesion in the microvessels of the ileum, which was partially blocked by anti-α4β1 integrin antibody in vivo. The expression of ICAM-1 and VCAM-1 was significantly enhanced by DCA in vitro, which was partially suppressed by the sphingosine-1-phosphate receptor 2 (S1PR2) antagonist. The S1PR2 antagonist significantly ameliorated IND-induced and DCA-exaggerated small intestinal injury.. DCA exacerbated IND-induced small intestinal enteropathy. DCA directly acts on the vascular endothelium and enhances the expression levels of adhesion molecules partially via S1PR2, leading to enhanced small intestinal lymphocyte migration.

Topics: Animals; Bile Acids and Salts; Cell Movement; Cholic Acids; Deoxycholic Acid; Disease Models, Animal; Endothelium, Vascular; Ileitis; Ileum; Intercellular Adhesion Molecule-1; Intestine, Small; Intravital Microscopy; Lymphocytes; Male; Mice; Mice, Inbred C57BL; Microvessels; Rats; Rats, Wistar; Sphingosine-1-Phosphate Receptors; Splanchnic Circulation; Vascular Cell Adhesion Molecule-1

Topics: Administration, Oral; Adolescent; Adult; Aged; Bile Acids and Salts; Crohn Disease; Deoxycholic Acid; Female; Humans; Ileitis; Ileostomy; Male; Middle Aged; Postoperative Period; Ursodeoxycholic Acid

Bile acids are supposed to promote colonic cancer. In Crohn's disease, colonic carcinomas are relatively rare. We, therefore, compared ileal and right colonic mucosal bile acids analysed by gas-liquid chromatography in 8 patients with ileal Crohn's disease (14-48 yrs.) and 7 patients with right colonic carcinoma (28-77 yrs.) who underwent surgery. In both ileal and colonic mucosa, nonsulphated bile acid concentrations were somewhat higher in Crohn's disease (20.98 micrograms/g +/- 4.77 SEM; 12.09 micrograms/g +/- 2.55) than in colonic carcinoma (16.06 micrograms/g +/- 3.46; 7.75 micrograms/g +/- 4.28). In ileal mucosa, percentages of lithocholic and deoxycholic acids were slightly higher in colonic carcinoma (3.9%; 23.2%) than in Crohn's disease (1.1%; 14.9%). In colonic mucosa, carcinoma patients had more lithocholic (7.6%) and less deoxycholic acid (11.9%) than patients with Crohn's disease (1.7%; 20.3%). Bile acid sulphate esters were similar in both diseases (ca. 3.0 micrograms/g in ileal, 1.4 micrograms/g in colonic mucosa). Our results show that ileal and right colonic mucosal nonsulphated bile acids tend to be even lower in right colonic carcinoma than in Crohn's disease. This agrees well with our earlier findings of low mucosal bile acid concentrations in patients with left colonic carcinoma (Tokai J Exp Clin Med 8: 59-69, 1983) and does not support the assumption that bile acids are envolved in right colonic carcinogenesis.

Topics: Adolescent; Adult; Aged; Bile Acids and Salts; Chenodeoxycholic Acid; Cholic Acids; Colon; Colonic Neoplasms; Crohn Disease; Deoxycholic Acid; Female; Humans; Ileitis; Ileum; Intestinal Mucosa; Lithocholic Acid; Male; Middle Aged; Ursodeoxycholic Acid

The metabolism of cholic acid and chenodeoxycholic acid was studied in seventeen patients with non-operated Crohn's disease, eleven ileitis and six ileocolitis patients. The turnover of cholic acid was significantly increased in patients with ileitis (k = 2.01 +/- 1.13 days-1; P less than 0.001) and ileocolitis (k = 0.91 +/- 0.47 days-1; P less than 0.005) as compared to normals (k = 0.35 +/- 0.19 days-1). Although chenodeoxycholic acid was better preserved in the enterohepatic circulation than cholic acid its turnover was also significantly faster in ileitis (k = 0.81 +/- 0.56 days-1; P less than 0.005) and ileocolitis patients (k = 0.62 +/- 0.18 days-1; P less than 0.01) than in normals (k = 0.20 +/- 0.09 days-1). The fractional turnover of cholic acid was related to the length of ileal involvement (r = 0.761; P less than 0.001; n = 17). Patients with Crohn's ileitis tended to preserve normal fasting total bile acid pools by increased synthesis of primary bile acids and efficient absorption of deoxycholic acid and ursodeoxycholic acid by the normal colon. Patients with active ileocolitis had decreased total fasting pool sizes (2.62 +/- 1.83 mmol; P less than 0.001) as compared to normals (7.69 +/- 1.61 mmol). In these patients there was no increase in bile acid synthesis as compared to normals and secondary bile acids were absent from bile. It is concluded that the colon has an important role in maintaining the fasting pool size to a normal level in the presence of an interrupted enterohepatic circulation of bile acids due to ileal disease.

Topics: Adolescent; Adult; Bile Acids and Salts; Chenodeoxycholic Acid; Cholic Acids; Crohn Disease; Deoxycholic Acid; Female; Humans; Ileitis; Kinetics; Male; Middle Aged; Ursodeoxycholic Acid

Biliary cholesterol saturation has been correlated with disease variables that might effect bile acid loss in ileitis patients with (N = 9) or without (N = 8) intestinal resection having a defined prevalence of gallstones. In addition, cholesterol saturation was determined in ulcerative colitis patients (N = 7) and gallstone patients (N = 18) as well as in 5 normal controls. Biliary cholesterol saturation in ileitis patients both with and without resection was similar to that in gallstone patients yet the prevalence of gallstones was only 12%. Cholesterol saturation did not correlate with ileal resection nor the extent, duration, or activity of ileitis. Biliary cholesterol saturation was not different in ulcerative colitis patients from that in normal subjects. It is concluded that cholesterol saturation of bile alone does not account for the high prevalence of cholesterol gallstones that has been reported in ileitis patients.

Topics: Adult; Bile; Chenodeoxycholic Acid; Cholelithiasis; Cholesterol; Deoxycholic Acid; Humans; Ileitis; Middle Aged