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Obeticholic acid reduces bacterial translocation and inhibits intestinal inflammation in cirrhotic rats
- Source :
- Journal of Hepatology. 64:1049-1057
- Publication Year :
- 2016
- Publisher :
- Elsevier BV, 2016.
-
Abstract
- In advanced cirrhosis, gut bacterial translocation is the consequence of intestinal barrier disruption and leads to bacterial infection. Bile acid abnormalities in cirrhosis could play a role in the integrity of the intestinal barrier and the control of microbiota, mainly through the farnesoid X receptor. We investigated the long-term effects of the farnesoid X receptor agonist, obeticholic acid, on gut bacterial translocation, intestinal microbiota composition, barrier integrity and inflammation in rats with CCl4-induced cirrhosis with ascites.Cirrhotic rats received a 2-week course of obeticholic acid or vehicle starting once ascites developed. We then determined: bacterial translocation by mesenteric lymph node culture, ileum expression of antimicrobial peptides and tight junction proteins by qPCR, fecal albumin loss, enteric bacterial load and microbiota composition by qPCR and pyrosequencing of ileum mucosa-attached contents, and intestinal inflammation by cytometry of the inflammatory infiltrate.Obeticholic acid reduced bacterial translocation from 78.3% to 33.3% (p0.01) and upregulated the expression of the farnesoid X receptor-associated gene small heterodimer partner. Treatment improved ileum expression of antimicrobial peptides, angiogenin-1 and alpha-5-defensin, tight junction proteins zonulin-1 and occludin, and reduced fecal albumin loss and liver fibrosis. Enteric bacterial load normalized, and the distinctive mucosal microbiota of cirrhosis was reduced. Gut immune cell infiltration was reduced and inflammatory cytokine and Toll-like receptor 4 expression normalized.In ascitic cirrhotic rats, obeticholic acid reduces gut bacterial translocation via several complementary mechanisms at the intestinal level. This agent could be used as an alternative to antibiotics to prevent bacterial infection in cirrhosis.
- Subjects :
- Male
0301 basic medicine
medicine.medical_specialty
Cirrhosis
medicine.drug_class
Ileum
Biology
Chenodeoxycholic Acid
Liver Cirrhosis, Experimental
digestive system
Microbiology
Rats, Sprague-Dawley
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Internal medicine
Chenodeoxycholic acid
medicine
Animals
Mesenteric lymph nodes
Intestinal Mucosa
Inflammation
Hepatology
Bile acid
Obeticholic acid
medicine.disease
Rats
Intestines
030104 developmental biology
medicine.anatomical_structure
Endocrinology
chemistry
Cytokines
030211 gastroenterology & hepatology
Farnesoid X receptor
Dysbiosis
Subjects
Details
- ISSN :
- 01688278
- Volume :
- 64
- Database :
- OpenAIRE
- Journal :
- Journal of Hepatology
- Accession number :
- edsair.doi.dedup.....766f95cc29ebcdeda6936f58291c60d4