Saccharomyces boulardii Protease Inhibits the Effects of Clostridium difficile Toxins A and B in Human Colonic Mucosa

Abstract

Saccharomyces boulardii is a nonpathogenic yeast used in the treatment of Clostridium difficile diarrhea and colitis. We have reported that S. boulardii inhibitsC. difficile toxin A enteritis in rats by releasing a 54-kDa protease which digests the toxin A molecule and its brush border membrane (BBM) receptor (I. Castagliuolo, J. T. LaMont, S. T. Nikulasson, and C. Pothoulakis, Infect. Immun. 64:5225–5232, 1996). The aim of this study was to further evaluate the role of S. boulardii protease in preventing C. difficile toxin A enteritis in rat ileum and determine whether it protects human colonic mucosa from C. difficile toxins. A polyclonal rabbit antiserum raised against purified S. boulardii serine protease inhibited by 73% the proteolytic activity present in S. boulardii conditioned medium in vitro. The anti-protease immunoglobulin G (IgG) prevented the action of S. boulardiion toxin A-induced intestinal secretion and mucosal permeability to [3H]mannitol in rat ileal loops, while control rabbit IgG had no effect. The anti-protease IgG also prevented the effects ofS. boulardii protease on digestion of toxins A and B and on binding of [3H]toxin A and [3H]toxin B to purified human colonic BBM. Purified S. boulardii protease reversed toxin A- and toxin B-induced inhibition of protein synthesis in human colonic (HT-29) cells. Furthermore, toxin A- and B-induced drops in transepithelial resistance in human colonic mucosa mounted in Ussing chambers were reversed by 60 and 68%, respectively, by preexposing the toxins to S. boulardii protease. We conclude that the protective effects of S. boulardii onC. difficile-induced inflammatory diarrhea in humans are due, at least in part, to proteolytic digestion of toxin A and B molecules by a secreted protease.

Application ofSaccharomyces cerevisiae var. boulardiiin food processing: a review

“…Some mechanisms through which S. boulardii make its therapeutic action is by liberating polyamines that stimulate the reparation of intestinal cells and the synthesis of the colonic mucosae, which increase the generation of short-chain fatty acids and enzymes which hydrolyse several disaccharides (lactase, maltase and sucrase or invertase; Profir et al 2015). Saccharomyces boulardii proteases are known to inhibit Toxin A and Toxin B of C. difficile, which are mainly responsible for diarrhoea and colitis (Castagliuolo et al 1999).…”

Systematic review with meta‐analysis: Saccharomyces boulardii in the prevention of antibiotic‐associated diarrhoea

“…34,35 One of the mechanisms, which has been demonstrated in animals, involves the production of a 54 kDa serine protease that inactivates a receptor for toxin A of C. difficile and directly degrades C. difficile toxins A and B. 36 Another mechanism involves secretion of increased levels of secretory immunoglobulin A (IgA) and IgA antitoxin A. 37 Moreover, both in vitro and in vivo studies have shown that S. boulardii exerts its anti-inflammatory activity, in part, by modulating host MAP kinase signalling pathways.…”

Probiotics: A Critical Review of Their Potential Role as Antihypertensives, Immune Modulators, Hypocholesterolemics, and Perimenopausal Treatments

“…boulardii was believed to protect animals against Clostridium difficile intestinal disease via degradation of the toxin receptor on the intestinal mucosa. 24 Helicobacter pylori, a major cause of gastric inflammation and ulceration, was reportedly suppressed by strains of L. reuteri that share similar glycolipid specificity, and therefore could inhibit binding of the pathogen to the glycolipid receptors. 25…”