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

Zora Teltschik, Reiner Wiest, Julia Beisner, Sabine Nuding, Claudia Hofmann, Juergen Schoelmerich, Charles L Bevins, Eduard F. Stange, Jan Wehkamp

Research output: Contribution to journalArticle

84 Citations (Scopus)

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, CCl 4-induced ascitic cirrhosis and 2-day portal vein-ligated (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 α-cryptdins and β-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 α-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 liver-gut axis including the underlying mechanisms could help us to find new treatment avenues.

Original languageEnglish (US)
Pages (from-to)1154-1163
Number of pages10
JournalHepatology
Volume55
Issue number4
DOIs
StatePublished - Apr 2012

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Paneth Cells
Bacterial Translocation
Fibrosis
Portal Vein
Ileum
Microbiological Techniques
Defensins
Endotoxemia
Cecum
Portal Hypertension
Liver Cirrhosis
Real-Time Polymerase Chain Reaction
Rodentia
Flow Cytometry
Lymph Nodes

ASJC Scopus subject areas

  • Hepatology

Cite this

Teltschik, Z., Wiest, R., Beisner, J., Nuding, S., Hofmann, C., Schoelmerich, J., ... Wehkamp, J. (2012). Intestinal bacterial translocation in rats with cirrhosis is related to compromised paneth cell antimicrobial host defense. Hepatology, 55(4), 1154-1163. https://doi.org/10.1002/hep.24789

Intestinal bacterial translocation in rats with cirrhosis is related to compromised paneth cell antimicrobial host defense. / Teltschik, Zora; Wiest, Reiner; Beisner, Julia; Nuding, Sabine; Hofmann, Claudia; Schoelmerich, Juergen; Bevins, Charles L; Stange, Eduard F.; Wehkamp, Jan.

In: Hepatology, Vol. 55, No. 4, 04.2012, p. 1154-1163.

Research output: Contribution to journalArticle

Teltschik, Z, Wiest, R, Beisner, J, Nuding, S, Hofmann, C, Schoelmerich, J, Bevins, CL, Stange, EF & Wehkamp, J 2012, 'Intestinal bacterial translocation in rats with cirrhosis is related to compromised paneth cell antimicrobial host defense', Hepatology, vol. 55, no. 4, pp. 1154-1163. https://doi.org/10.1002/hep.24789
Teltschik, Zora ; Wiest, Reiner ; Beisner, Julia ; Nuding, Sabine ; Hofmann, Claudia ; Schoelmerich, Juergen ; Bevins, Charles L ; Stange, Eduard F. ; Wehkamp, Jan. / Intestinal bacterial translocation in rats with cirrhosis is related to compromised paneth cell antimicrobial host defense. In: Hepatology. 2012 ; Vol. 55, No. 4. pp. 1154-1163.
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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, CCl 4-induced ascitic cirrhosis and 2-day portal vein-ligated (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 α-cryptdins and β-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 α-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 liver-gut axis including the underlying mechanisms could help us to find new treatment avenues.",
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