Clostridium perfringens Epsilon Toxin Increases the Small Intestinal Permeability in Mice and Rats

JORGE GOLDSTEIN, WINSTON E. MORRIS, CÉSAR FABIÁN LOIDL, CARLA TIRONI- FARINATTI, BRUCE A. MCCLANE, FRANCISCO A. UZAL, MARIANO E. FERNANDEZ MIYAKAWA

PLOS ONE

PLos

Lugar: San Francisco; Año: 2009 vol. 4 p. 1 - 11

1932-6203

Epsilon toxin is a potent neurotoxin produced by Clostridium perfringens types B and D,an anaerobic bacterium that causes enterotoxaemia in ruminants. In the affected animal, itcauses oedema of the lungs and brain by damaging the endothelial cells, inducingphysiological and morphological changes. Although it is believed to compromise theintestinal barrier, thus entering the gut vasculature, little is known about the mechanismunderlying this process. This study characterizes the effects of epsilon toxin on fluidtransport and bioelectrical parameters in the small intestine of mice and rats. Theenteropooling and the intestinal loop tests, together with the single-pass perfusion assayand in vitro and ex vivo analysis in Ussing’s chamber, were all used in combination withhistological and ultrastructural analysis of mice and rat small intestine, challenged with orwithout C. perfringens epsilon toxin. Luminal epsilon toxin induced a time andconcentration dependent intestinal fluid accumulation and fall of the transepithelialresistance. Although no evident histological changes were observed, opening of themucosa tight junction in combination with apoptotic changes in the lamina propria wereseen with transmission electron microscopy. These results indicate that C. perfringensepsilon toxin alters the intestinal permeability, predominantly by opening the mucosatight junction, increasing its permeability to macromolecules, and inducing furtherdegenerative changes in the lamina propria of the bowel.