Saccharomyces boulardii ameliorates Citrobacter rodentium-induced colitis through actions on bacterial virulence factors.
Saccharomyces boulardii has received increasing attention as a probiotic effective in the prevention and treatment of infectious and inflammatory bowel diseases. The aim of this study was to examine the ameliorating effects of S. boulardii on Citrobacter rodentium colitis in vivo and identify potential mechanisms of action. C57BL/6 mice received 2.5 x 10(8) C. rodentium by gavage on day 0, followed by S. boulardii (25 mg; 5 x 10(8) live cells) gavaged twice daily from day 2 to day 9. Animal weights were monitored until death on day 10. Colons were removed and assessed for epithelial barrier function, histology, and myeloperoxidase activity. Bacterial epithelial attachment and type III secreted proteins translocated intimin receptor Tir (the receptor for bacterial intimin) and EspB (a translocation apparatus protein) required for bacterial virulence were assayed. In infected mice, S. boulardii treatment significantly attenuated weight loss, ameliorated crypt hyperplasia (234.7 +/- 7.2 vs. 297.8 +/- 17.6 microm) and histological damage score (0.67 +/- 0.67 vs. 4.75 +/- 0.75), reduced myeloperoxidase activity (2.1 +/- 0.4 vs. 4.7 +/- 0.9 U/mg), and attenuated increased mannitol flux (17.2 +/- 5.0 vs. 31.2 +/- 8.2 nm.cm(-2).h(-1)). The ameliorating effects of S. boulardii were associated with significantly reduced numbers of mucosal adherent C. rodentium, a marked reduction in Tir protein secretion and translocation into mouse colonocytes, and a striking reduction in EspB expression and secretion. We conclude that S. boulardii maintained colonic epithelial barrier integrity and ameliorated inflammatory sequelae associated with C. rodentium infection by attenuating C. rodentium adherence to host epithelial cells through putative actions on the type III secretion system.
Wu
X
X
Div. of Gastroenterology, BC Children's Hospital, 4480 Oak St., Rm. K4-181, Vancouver, BC, Canada V6H 3V4.
Vallance
B A
BA
Boyer
L
L
Bergstrom
K S B
KS
Walker
J
J
Madsen
K
K
O'Kusky
J R
JR
Buchan
A M
AM
Jacobson
K
K
D018829:Adhesins, Bacterial / Q000378:metabolism; D000818:Animals; D001422:Bacterial Adhesion; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D018988:Bacterial Translocation; D044082:Citrobacter rodentium / Q000235:genetics / Q000254:growth & development / Q000378:metabolism / Q000472:pathogenicity*; D003092:Colitis / Q000378:metabolism / Q000382:microbiology / Q000473:pathology / Q000517:prevention & control*; D003106:Colon / Q000382:microbiology* / Q000648:ultrastructure; D004756:Enterobacteriaceae Infections / Q000150:complications / Q000378:metabolism / Q000382:microbiology / Q000473:pathology / Q000517:prevention & control*; D007413:Intestinal Mucosa / Q000382:microbiology / Q000648:ultrastructure; D008353:Mannitol / Q000378:metabolism; D008564:Membrane Potentials; D051379:Mice; D008810:Mice, Inbred C57BL; D010539:Permeability; D009195:Peroxidase / Q000378:metabolism; D019936:Probiotics / Q000627:therapeutic use*; D011956:Receptors, Cell Surface / Q000378:metabolism; D012440:Saccharomyces / Q000254:growth & development*; D013997:Time Factors; D014158:Transcription, Genetic; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
D018829:Adhesins, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D011956:Receptors, Cell Surface; D037521:Virulence Factors; D008353:Mannitol; D009195:Peroxidase