Saccharomyces Boulardii effects on gastrointestinal diseases 47 Saccharomyces boulardii effects on gastrointestinal diseases

Health benefits attributed to probiotics have been described for decades. They include the treatment and the prevention of gastrointestinal diseases, vaginal and urinary infections and allergies. Saccharomyces boulardii, a species of yeast widely distributed, has been described as a biotherapeutic agent since several clinical trials displayed its beneficial effects in the prevention and the treatment of intestinal infections and in the maintenance of inflammatory bowel disease. All these diseases are characterized by acute diarrhoea. Administration of the yeast in combination or not with an antibiotherapy has shown to decrease significantly the duration and the frequency of diarrhoea. Experimental studies elucidated partially the molecular mechanisms triggered to improve the host health. The discovery of its anti-inflammatory and immuno-modulatory activities in correlation with the advances in the understanding of mucosal immunology opens a new field of perspectives in S. boulardii therapeutic applications. Introduction The intestine contains a complex and dynamic microflora including more than 2000 micro-organism species coexisting in a complex equilibrium with the host. This microflora has various effects including metabolic activities, trophic effects on the intestinal epithelium, interactions with the host immune system (Guarner and Malagelada, 2003) and acts as a barrier to prevent colonization by opportunistic and pathogenic micro-organisms (Vollaard and Clasener, 1994). The immune system and particularly the gut-associated lymphoid tissues (GALT) provides the host with protective mechanisms against pathogen invasion across the intestinal mucosal surface (Acheson and Luccioli, 2004). However, disequilibrium in the gut microflora ecology and in the immune response could induce gastrointestinal diseases. The term “probiotic” has been firstly defined by Fuller as “a live microbial feed supplement which beneficially affects the host by improving its intestinal microbial balance” (Fuller, 1989). This definition has been extended to health and probiotics were redefined as “live micro-organisms that, when administered in adequate amounts, confer a health benefit to the host” (FAO/WHO, 2001). Saccharomyces Boulardii, isolated from litchi fruit by Henri Boulard in the 1920s, belongs to the Saccharomyces genus which is commonly used in several food processes including beverages and bred fermentation. This yeast is frequently prescribed in a lyophilized form as a biotherapeutic agent (Elmer et al., 1996; Klein et al., 1993). Indeed, controlled clinical trials have shown that oral administration of S. boulardii could treat or prevent gastrointestinal diseases such as antibiotic-associated diarrhoea (Kotowska et al., 2005), recurrent Clostridium difficile-associated diseases (McFarland, 2006), traveller’s diarrhoea (McFarland, 2007), children acute diarrhoea (Htwe et al., 2008), enteral tube feeding-associated diarrhoea (Bleichner et al., 1997), AIDSassociated diarrhoea (Saint-Marc et al., 1991), intestinal bowel disease such as Crohn’s disease and ulcerative colitis (Guslandi et al., 2003; Guslandi et al., 2000) and irritable bowel syndrome (Maupas et al., 1983). S. boulardii and S. cerevisiae are members of the same species (Edwards-Ingram et al., 2007) but they differ genetically, metabolically and physiologically (Fietto et al., 2004; Hennequin et al., 2001). S. boulardii is characterized by a specific microsatellite allele (Hennequin et al., 2001) and recent studies showed that S. boulardii genome presents trisomy of the chromosome 9, altered copy numbers of genes potentially contributing to the increased growth rate and a better survival in acidic environment (Edwards-Ingram et al., 2007). In addition to a better resistance to acidic stress, S. boulardii grows faster than S. cerevisiae at 37°C (Fietto et al., 2004). Pharmacokinetic studies have shown that after oral administration of lyophilized S. boulardii, the steady-state concentrations are achieved in the colon within 3 days, and the yeast are cleared from the stools within 2-5 days after discontinuation (Blehaut et al., 1989). S. boulardii displays important characteristics allowing a micro-organism to transit through the gastrointestinal tract and to be used as a probiotic. During the intestinal transit, S. boulardii interacts with resident microflora and intestinal mucosa. Moreover, experimental studies displayed that S. boulardii induces a protection against enteric pathogens (Czerucka and Rampal, 2002; Mumy et al., 2007), modulates the host immune response (Ozkan et al., 2007; Rodrigues et al., 2000), decreases inflammation (Lee et al., 2005; Sougioultzis et al., 2006) and hydroelectrolytic secretions (Czerucka and Rampal, 1999), inhibits bacterial toxins (Castagliuolo et al., 1999; Tasteyre et al., 2002) and enhances trophic factors such as brush border membrane enzymes and nutrient transporters (Buts et al., 1986; Buts et al., 1994). The aim of this review is to summarize the current knowledge about the beneficial effects of S. boulardii on gastrointestinal diseases. Firstly, clinical trials will be succinctly reviewed. Then, the experimental studies which have lead to a better understanding of the mechanisms used by the yeast to prevent and/or treat gastrointestinal diseases will be extensively described. Corresponding author: Email: salmon@tours.inra. fr. Phone: +(33)-247427891; Fax: +(33)-247427779. Horizon Scientific Press. http://www.horizonpress. com Curr. Issues Mol. Biol. 11: 47-58. O line journal at http://www.cimb. org