title: Gut microbiota, tight junction protein expression, intestinal resistance, bacterial translocation and mortality following cholestasis depend on the genetic background of the host.
abstract: Failure of the intestinal barrier is a characteristic feature of cholestasis. We have previously observed higher mortality in C57BL/6J compared with A/J mice following common bile duct ligation (CBDL). We hypothesized the alteration in gut barrier function following cholestasis would vary by genetic background. Following one week of CBDL, jejunal TEER was significantly reduced in each ligated mouse compared with their sham counterparts; moreover, jejunal TEER was significantly lower in both sham and ligated C57BL/6J compared with sham and ligated A/J mice, respectively. Bacterial translocation to mesenteric lymph nodes was significantly increased in C57BL/6J mice vs. A/J mice. Four of 15 C57BL/6J mice were bacteremic; whereas, none of the 17 A/J mice were. Jejunal IFN-γ mRNA expression was significantly elevated in C57BL/6J compared with A/J mice. Western blot analysis demonstrated a significant decrease in occludin protein expression in C57BL/6J compared with A/J mice following both sham operation and CBDL. Only C57BL/6J mice demonstrated a marked decrease in ZO-1 protein expression following CBDL compared with shams. Pyrosequencing of the 16S rRNA gene in fecal samples showed a dysbiosis only in C57BL/6J mice following CBDL when compared with shams. This study provides evidence of strain differences in gut microbiota, tight junction protein expression, intestinal resistance and bacterial translocation which supports the notion of a genetic predisposition to exaggerated injury following cholestasis.
authors: Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA. salaish@smail.umaryland.edu
authors: Samuel M
authors: SM
authors: Alaish
authors: Alexis D
authors: AD
authors: Smith
authors: Jennifer
authors: J
authors: Timmons
authors: Jose
authors: J
authors: Greenspon
authors: Daniel
authors: D
authors: Eyvazzadeh
authors: Ebony
authors: E
authors: Murphy
authors: Terez
authors: T
authors: Shea-Donahue
authors: Shana
authors: S
authors: Cirimotich
authors: Emmanuel
authors: E
authors: Mongodin
authors: Aiping
authors: A
authors: Zhao
authors: Alessio
authors: A
authors: Fasano
authors: James P
authors: JP
authors: Nataro
authors: Alan
authors: A
authors: Cross
mesh_terms: D000818:Animals; D016470:Bacteremia / Q000235:genetics* / Q000401:mortality*; D018988:Bacterial Translocation / Q000235:genetics*; D002779:Cholestasis / Q000150:complications*; D041981:Gastrointestinal Tract / Q000276:immunology* / Q000382:microbiology*; D020022:Genetic Predisposition to Disease; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D062725:Tight Junction Proteins / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D062725:Tight Junction Proteins
keywords: bacterial translocation; bile duct ligation; cholestasis; interferon-gamma; intestinal microbiota; transepithelial electric resistance
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