Probiotic Escherichia coli Nissle 1917 inhibits leaky gut by enhancing mucosal integrity.
BACKGROUND
Probiotics are proposed to positively modulate the intestinal epithelial barrier formed by intestinal epithelial cells (IECs) and intercellular junctions. Disruption of this border alters paracellular permeability and is a key mechanism for the development of enteric infections and inflammatory bowel diseases (IBDs).


RESULTS
To study the in vivo effect of probiotic Escherichia coli Nissle 1917 (EcN) on the stabilization of the intestinal barrier under healthy conditions, germfree mice were colonized with EcN or K12 E. coli strain MG1655. IECs were isolated and analyzed for gene and protein expression of the tight junction molecules ZO-1 and ZO-2. Then, in order to analyze beneficial effects of EcN under inflammatory conditions, the probiotic was orally administered to BALB/c mice with acute dextran sodium sulfate (DSS) induced colitis. Colonization of gnotobiotic mice with EcN resulted in an up-regulation of ZO-1 in IECs at both mRNA and protein levels. EcN administration to DSS-treated mice reduced the loss of body weight and colon shortening. In addition, infiltration of the colon with leukocytes was ameliorated in EcN inoculated mice. Acute DSS colitis did not result in an anion secretory defect, but abrogated the sodium absorptive function of the mucosa. Additionally, intestinal barrier function was severely affected as evidenced by a strong increase in the mucosal uptake of Evans blue in vivo. Concomitant administration of EcN to DSS treated animals resulted in a significant protection against intestinal barrier dysfunction and IECs isolated from these mice exhibited a more pronounced expression of ZO-1.


CONCLUSIONS
This study convincingly demonstrates that probiotic EcN is able to mediate up-regulation of ZO-1 expression in murine IECs and confer protection from the DSS colitis-associated increase in mucosal permeability to luminal substances.
Ukena
Sya N
SN
Department of Mucosal Immunity, Helmholtz Centre for Infection Research, Braunschweig, Germany.
Singh
Anurag
A
Dringenberg
Ulrike
U
Engelhardt
Regina
R
Seidler
Ursula
U
Hansen
Wiebke
W
Bleich
André
A
Bruder
Dunja
D
Franzke
Anke
A
Rogler
Gerhard
G
Suerbaum
Sebastian
S
Buer
Jan
J
Gunzer
Florian
F
Westendorf
Astrid M
AM
D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D003092:Colitis / Q000503:physiopathology / Q000628:therapy*; D017931:DNA Primers; D004926:Escherichia coli; D005260:Female; D005455:Fluorescent Antibody Technique; D005856:Germ-Free Life; D007413:Intestinal Mucosa / Q000503:physiopathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D019936:Probiotics
D017931:DNA Primers