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Intestinal bacterial translocation in cirrhotic rats is related to compromised paneth cell antimicrobial host defence.
MedLine Citation:
PMID:  22095436     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Liver cirrhosis is associated with bacterial translocation (BT) and endotoxemia. Most translocating bacteria belong to the common intestinal microbiota suggesting a breakdown of intestinal barrier function. Herein, we hypothesised that diminished mucosal antimicrobial host defence could predispose to BT. METHODS: Two rodent models of portal hypertension with increased BT were used, CCl(4) -induced ascitic cirrhosis and 2-day portal-vein ligated animals (PVL). BT was assessed by standard microbiological techniques on mesenteric lymph nodes. Total RNA was isolated systematically throughout the intestinal tract and expression of Paneth cell α-cryptdins and ß-defensins was determined by qRT PCR. To determine functional consequences, mucosal antimicrobial activity was assessed with FACS assay. RESULTS: BT was detectable in 40% of cirrhotic rats. Compared to the group without BT these animals exhibited diminished intestinal Paneth cell α-cryptdin 5 and 7 expression. In contrast, portal vein ligation was associated with BT in all animals but did not affect antimicrobial peptides. The decrease of Paneth cell antimicrobials was most pronounced in the ileum and the coecum. Other antimicrobials showed no changes or even an induction in case of BT at different sites. Antimicrobial activity towards different commensal strains was reduced especially in the distal ileum and the coecum in experimental cirrhosis with BT (excluding portal vein ligation). CONCLUSION: Compromised Paneth cell antimicrobial host defence seems to predispose to BT in experimental cirrhosis. Understanding this liver- gut axis including the underlying mechanisms could help to find new treatment avenues. (HEPATOLOGY 2011.).
Authors:
Zora Teltschik; Reiner Wiest; Julia Beisner; Sabine Nuding; Claudia Hofmann; Juergen Schoelmerich; Charles L Bevins; Eduard F Stange; Jan Wehkamp
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-11-16
Journal Detail:
Title:  Hepatology (Baltimore, Md.)     Volume:  -     ISSN:  1527-3350     ISO Abbreviation:  -     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-11-18     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8302946     Medline TA:  Hepatology     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 American Association for the Study of Liver Diseases.
Affiliation:
Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart and University of Tuebingen, Germany.
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