Probiotic bacteria enhance murine and human intestinal epithelial barrier function.
OBJECTIVE
The probiotic compound, VSL#3, is efficacious as maintenance therapy in pouchitis and ulcerative colitis. The aim of this study was to determine the efficacy of VSL#3 as a primary therapy in the treatment of colitis in the interleukin (IL)-10 gene-deficient mouse. Mechanisms of action of VSL#3 were investigated in T(84) monolayers.


METHODS
IL-10 gene-deficient and control mice received 2.8 x 10(8) colony-forming units per day of VSL#3 for 4 weeks. Colons were removed and analyzed for cytokine production, epithelial barrier function, and inflammation. VSL#3 or conditioned media was applied directly to T(84) monolayers.


RESULTS
Treatment of IL-10 gene-deficient mice with VSL#3 resulted in normalization of colonic physiologic function and barrier integrity in conjunction with a reduction in mucosal secretion of tumor necrosis factor alpha and interferon gamma and an improvement in histologic disease. In vitro studies showed that epithelial barrier function and resistance to Salmonella invasion could be enhanced by exposure to a proteinaceous soluble factor secreted by the bacteria found in the VSL#3 compound.


CONCLUSIONS
Oral administration of VSL#3 was effective as primary therapy in IL-10 gene-deficient mice, and had a direct effect on epithelial barrier function.
Madsen
K
K
Division of Gastroenterology, University of Alberta, Edmonton, Alberta, Canada. karen.madsen@Ualberta.ca
Cornish
A
A
Soper
P
P
McKaigney
C
C
Jijon
H
H
Yachimec
C
C
Doyle
J
J
Jewell
L
L
De Simone
C
C
D000818:Animals; D001644:Bifidobacterium; D002460:Cell Line; D003092:Colitis / Q000378:metabolism / Q000628:therapy*; D004847:Epithelial Cells / Q000378:metabolism / Q000382:microbiology; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics; D016209:Interleukin-8 / Q000378:metabolism; D007408:Intestinal Absorption / Q000502:physiology*; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism* / Q000382:microbiology*; D007778:Lactobacillus; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D018408:Patch-Clamp Techniques; D019936:Probiotics / Q000494:pharmacology*; D012480:Salmonella Infections / Q000517:prevention & control / Q000628:therapy; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10