title: Oral bile acids reduce bacterial overgrowth, bacterial translocation, and endotoxemia in cirrhotic rats.
abstract: Experiments were performed to test whether conjugated bile acid administration would decrease bacterial overgrowth, bacterial translocation, and endotoxemia in ascitic cirrhotic rats. Cholylsarcosine, a deconjugation-dehydroxylation resistant and cholylglycine, a deconjugation-dehydroxylation susceptible bile acid were used. Rats with CCl(4)-induced cirrhosis and ascites were fed cholylsarcosine, cholylglycine (both at 70 mg/kg/d), or placebo for 2 weeks. Healthy rats, as controls, were treated similarly. In cirrhotic rats receiving placebo, bile secretion from an acute biliary fistula was lower than in healthy rats (27.2 +/- 6.5 vs. 53.0 +/- 3.1 microL/kg/min; mean +/- SE, P<.05). The administration of conjugated bile acids to cirrhotic rats normalized bile secretion (cholylsarcosine, 51.8 +/- 6.29; cholylglycine, 52.72 +/- 8.9 microL/kg/min). Total ileal bacterial content was 6-fold higher in ascitic cirrhotic rats than in healthy rats. Conjugated bile acid administration reduced bacterial content to normal levels. Bacterial translocation was less in cirrhotic animals receiving conjugated bile acids (cholylsarcosine, 33%; cholylglycine, 26%) than in animals receiving placebo (66%). Endotoxemia was decreased in cirrhotic rats by conjugated bile acid feeding (cholylsarcosine, 0.098 +/- 0.002; cholylglycine 0.101 +/- 0.007 EU/mL) compared with placebo (0.282 +/- 0.124, P <.001). Survival was greater in animals receiving conjugated bile acids (cholylsarcosine, 10/15; cholylglycine, 11/15; placebo, 5/15). In conclusion, the administration of conjugated bile acids to ascitic cirrhotic rats increased bile acid secretion, eliminated intestinal bacterial overgrowth, decreased bacterial translocation, decreased endotoxemia, and increased survival. Oral conjugated bile acids may be useful in preventing bacterial translocation, endotoxemia, and spontaneous bacterial perotonitis in cirrhotic patients.
authors.affiliation: Departments of Gastroenterology, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain.
authors.forename: Vicente
authors.initials: V
authors.lastname: Lorenzo-Zúñiga
authors.forename: Ramón
authors.initials: R
authors.lastname: Bartolí
authors.forename: Ramón
authors.initials: R
authors.lastname: Planas
authors.forename: Alan F
authors.initials: AF
authors.lastname: Hofmann
authors.forename: Belén
authors.initials: B
authors.lastname: Viñado
authors.forename: Lee R
authors.initials: LR
authors.lastname: Hagey
authors.forename: José M
authors.initials: JM
authors.lastname: Hernández
authors.forename: Josep
authors.initials: J
authors.lastname: Mañé
authors.forename: Marco A
authors.initials: MA
authors.lastname: Alvarez
authors.forename: Vicente
authors.initials: V
authors.lastname: Ausina
authors.forename: Miquel Angel
authors.initials: MA
authors.lastname: Gassull
mesh_terms: D000818:Animals; D001419:Bacteria / Q000254:growth & development*; D018988:Bacterial Translocation / Q000187:drug effects*; D001646:Bile / Q000187:drug effects / Q000378:metabolism; D001647:Bile Acids and Salts / Q000008:administration & dosage*; D002793:Cholic Acids / Q000008:administration & dosage; D019446:Endotoxemia / Q000188:drug therapy*; D006000:Glycocholic Acid / Q000008:administration & dosage; D007082:Ileum / Q000382:microbiology; D007422:Intestines / Q000382:microbiology*; D008106:Liver Cirrhosis, Experimental / Q000188:drug therapy / Q000382:microbiology*; D008297:Male; D010919:Placebos; D051381:Rats; D017207:Rats, Sprague-Dawley; D012521:Sarcosine / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D001647:Bile Acids and Salts; D002793:Cholic Acids; D010919:Placebos; D006000:Glycocholic Acid; C061997:cholylsarcosine; D012521:Sarcosine