title: Intestinal bacterial translocation in rats with cirrhosis is related to compromised Paneth cell antimicrobial host defense.
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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart and University of Tuebingen, Germany.
authors.forename: Zora
authors.initials: Z
authors.lastname: Teltschik
authors.forename: Reiner
authors.initials: R
authors.lastname: Wiest
authors.forename: Julia
authors.initials: J
authors.lastname: Beisner
authors.forename: Sabine
authors.initials: S
authors.lastname: Nuding
authors.forename: Claudia
authors.initials: C
authors.lastname: Hofmann
authors.forename: Juergen
authors.initials: J
authors.lastname: Schoelmerich
authors.forename: Charles L
authors.initials: CL
authors.lastname: Bevins
authors.forename: Eduard F
authors.initials: EF
authors.lastname: Stange
authors.forename: Jan
authors.initials: J
authors.lastname: Wehkamp
mesh_terms: D000818:Animals; D018988:Bacterial Translocation / Q000502:physiology*; D001441:Bacteroides fragilis / Q000502:physiology; D001644:Bifidobacterium / Q000502:physiology; D002251:Carbon Tetrachloride / Q000009:adverse effects; D002432:Cecum / Q000382:microbiology; D004195:Disease Models, Animal; D013293:Enterococcus faecalis / Q000502:physiology; D004926:Escherichia coli / Q000502:physiology; D006975:Hypertension, Portal / Q000209:etiology / Q000503:physiopathology; D007082:Ileum / Q000382:microbiology; D007422:Intestines / Q000382:microbiology*; D008026:Ligation / Q000009:adverse effects; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D019879:Paneth Cells / Q000378:metabolism* / Q000473:pathology; D011169:Portal Vein / Q000503:physiopathology; D011498:Protein Precursors / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D023083:beta-Defensins / Q000378:metabolism*
chemical_list: D011498:Protein Precursors; D023083:beta-Defensins; C059569:cryptdin; D002251:Carbon Tetrachloride