Intestinal bacterial translocation in rats with cirrhosis is related to compromised paneth cell antimicrobial host defense

Teltschik, Zora and Wiest, Reiner and Beisner, Julia and Nuding, Sabine and Hofmann, Claudia and Schoelmerich, Juergen and Bevins, Charles L. and Stange, Eduard F. and Wehkamp, Jan (2012) Intestinal bacterial translocation in rats with cirrhosis is related to compromised paneth cell antimicrobial host defense. HEPATOLOGY, 55 (4). pp. 1154-1163. ISSN 0270-9139,

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Abstract

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. We hypothesized that diminished mucosal antimicrobial host defense could predispose to BT. Two rodent models of portal hypertension with increased BT were used, CCl4-induced ascitic cirrhosis and 2-day portal veinligated (PVL) animals. 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 a-cryptdins and beta-defensins was determined by real-time quantitative polymerase chain reaction (qPCR). To determine functional consequences, mucosal antimicrobial activity was assessed with a fluorescence-activated cell sorting assay. BT was detectable in 40% of rats with cirrhosis. Compared with the group without BT, these animals exhibited diminished intestinal Paneth cell a-cryptdin 5 and 7 expression. In contrast, PVL was associated with BT in all animals but did not affect antimicrobial peptides. The decrease in Paneth cell antimicrobials was most pronounced in the ileum and the coecum. Other antimicrobials showed no changes or even an induction in the case of BT at different sites. Antimicrobial activity toward different commensal strains was reduced, especially in the distal ileum and the cecum in experimental cirrhosis with BT (excluding PVL). Conclusion: Compromised Paneth cell antimicrobial host defense seems to predispose to BT in experimental cirrhosis. Understanding this livergut axis including the underlying mechanisms could help us to find new treatment avenues. (HEPATOLOGY 2012)

Item Type: Article
Uncontrolled Keywords: CHRONIC PORTAL-HYPERTENSION; ILEAL CROHNS-DISEASE; LIVER-CIRRHOSIS; ALPHA-DEFENSINS; TRANSIT-TIME; NOD2 GENE; IN-VIVO; OVERGROWTH; PERITONITIS; EXPRESSION;
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Innere Medizin I
Depositing User: Dr. Gernot Deinzer
Date Deposited: 15 May 2020 11:40
Last Modified: 15 May 2020 11:40
URI: https://pred.uni-regensburg.de/id/eprint/18971

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