Gut microbiota, tight junction protein expression, intestinal resistance, bacterial translocation and mortality following cholestasis depend on the genetic background of the host

Samuel M. Alaish, Alexis D. Smith, Jennifer Timmons, Jose Greenspon, Daniel Eyvazzadeh, Ebony Murphy, Terez Shea-Donahue, Shana Cirimotich, Emmanuel Mongodin, Aiping Zhao, Alessio Fasano, James P. Nataro, Alan Cross

Research output: Contribution to journalArticlepeer-review

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 signifcantly reduced in each ligated mouse compared with their sham counterparts; moreover, jejunal TeeR was signifcantly lower in both sham and ligated c57BL/6J compared with sham and ligated A/J mice, respectively. Bacterial translocation to mesenteric lymph nodes was signifcantly 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 signifcantly elevated in c57BL/6J compared with A/J mice. Western blot analysis demonstrated a signifcant 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.

Original languageEnglish (US)
Pages (from-to)292-305
Number of pages14
JournalGut Microbes
Volume4
Issue number4
DOIs
StatePublished - Jul 2013
Externally publishedYes

Keywords

  • Bacterial translocation
  • Bile duct ligation
  • Cholestasis
  • Interferon-gamma
  • Intestinal microbiota
  • Transepithelial electric resistance

ASJC Scopus subject areas

  • Microbiology
  • Gastroenterology
  • Microbiology (medical)
  • Infectious Diseases

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