Saccharomyces boulardii inhibits Clostridium difficile toxin A binding and enterotoxicity in rat ileum.
BACKGROUND
Saccharomyces boulardii is a nonpathogenic yeast used for the prevention and treatment of Clostridium difficile-associated diarrhea and colitis. However, the mechanism by which S. boulardii exerts its protective effects remains unclear.


METHODS
The binding of [3H]toxin A to its brush border receptor preincubated with S. boulardii-cultured suspension or filtered conditioned medium was measured in vitro. The effect of toxin A on secretion, epithelial permeability, and morphology in rat ileal loops in vivo was also examined in rats pretreated with S. boulardii.


RESULTS
S. boulardii reduced [3H]toxin A-receptor binding in a dose-dependent fashion. Sodium dodecyl sulfate polyacrylamide gel electrophoresis of ileal brush border exposed to S. boulardii-conditioned medium revealed a diminution of all brush border proteins. Treatment of rats with S. boulardii suspension reduced fluid secretion and mannitol permeability caused by toxin A.


CONCLUSIONS
S. boulardii may reduce some of the enterotoxic effects of toxin A by inhibiting toxin A-receptor binding. This effect appears to be manifested by a secreted product of the yeast, possibly a protease.
Pothoulakis
C
C
Evans Memorial Department of Clinical Research, University Hospital, Boston University School of Medicine, Massachusetts.
Kelly
C P
CP
Joshi
M A
MA
Gao
N
N
O'Keane
C J
CJ
Castagliuolo
I
I
Lamont
J T
JT
D000818:Animals; D001427:Bacterial Toxins / Q000378:metabolism / Q000633:toxicity; D002846:Chromatography, Affinity; D016360:Clostridioides difficile; D004591:Electrophoresis, Polyacrylamide Gel; D004768:Enterotoxins / Q000378:metabolism* / Q000633:toxicity*; D007082:Ileum / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008353:Mannitol / Q000378:metabolism; D008565:Membrane Proteins / Q000302:isolation & purification / Q000378:metabolism*; D008871:Microvilli / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D008970:Molecular Weight; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D011971:Receptors, Immunologic / Q000302:isolation & purification / Q000378:metabolism*; D012440:Saccharomyces; D014316:Tritium
D001427:Bacterial Toxins; C080487:Clostridium difficile enterotoxin A receptor; D004768:Enterotoxins; D008565:Membrane Proteins; D011971:Receptors, Immunologic; C041348:tcdA protein, Clostridium difficile; D014316:Tritium; D008353:Mannitol