Probiotic Mixture VSL#3 Protects the Epithelial Barrier by Maintaining Tight Junction Protein Expression and Preventing Apoptosis in a Murine Model of Colitis

Am J Physiol Gastrointest Liver Physiol. 2009 May;296(5):G1140-9. doi: 10.1152/ajpgi.90534.2008. Epub 2009 Feb 12.

Abstract

Changes in epithelial tight junction protein expression and apoptosis increase epithelial permeability in inflammatory bowel diseases. The effect of the probiotic mixture VSL#3 on the epithelial barrier was studied in dextran sodium sulfate (DSS)-induced colitis in mice. Acute colitis was induced in BALB/c mice (3.5% DSS for 7 days). Mice were treated with either 15 mg VSL#3 or placebo via gastric tube once daily during induction of colitis. Inflammation was assessed by clinical and histological scores. Colonic permeability to Evans blue was measured in vivo. Tight junction protein expression and epithelial apoptotic ratio were studied by immunofluorescence and Western blot. VSL#3 treatment reduced inflammation (histological colitis scores: healthy control 0.94 +/- 0.28, DSS + placebo 14.64 +/- 2.55, DSS + VSL#3 8.43 +/- 1.82; P = 0.011). A pronounced increase in epithelial permeability in acute colitis was completely prevented by VSL#3 therapy [healthy control 0.4 +/- 0.07 (extinction/g), DSS + placebo 5.75 +/- 1.67, DSS + VSL#3 0.26 +/- 0.08; P = 0.003]. In acute colitis, decreased expression and redistribution of the tight junction proteins occludin, zonula occludens-1, and claudin-1, -3, -4, and -5 were observed, whereas VSL#3 therapy prevented these changes. VSL#3 completely prevented the increase of epithelial apoptotic ratio in acute colitis [healthy control 1.58 +/- 0.01 (apoptotic cells/1,000 epithelial cells), DSS + placebo 13.33 +/- 1.29, DSS + VSL#3 1.72 +/- 0.1; P = 0.012]. Probiotic therapy protects the epithelial barrier in acute colitis by preventing 1) decreased tight junction protein expression and 2) increased apoptotic ratio.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Animals
  • Apoptosis*
  • Claudin-1
  • Claudin-3
  • Claudin-4
  • Claudin-5
  • Colitis / chemically induced
  • Colitis / metabolism
  • Colitis / microbiology
  • Colitis / pathology
  • Colitis / therapy*
  • Colon / metabolism
  • Colon / microbiology*
  • Colon / pathology
  • Dextran Sulfate
  • Disease Models, Animal
  • Female
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / microbiology*
  • Intestinal Mucosa / pathology
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Permeability
  • Phosphoproteins / metabolism
  • Probiotics / administration & dosage*
  • Severity of Illness Index
  • Tight Junctions / metabolism
  • Tight Junctions / microbiology*
  • Tight Junctions / pathology
  • Time Factors
  • Zonula Occludens-1 Protein

Substances

  • Claudin-1
  • Claudin-3
  • Claudin-4
  • Claudin-5
  • Cldn1 protein, mouse
  • Cldn3 protein, mouse
  • Cldn4 protein, mouse
  • Cldn5 protein, mouse
  • Membrane Proteins
  • Phosphoproteins
  • Tjp1 protein, mouse
  • Zonula Occludens-1 Protein
  • Dextran Sulfate