Twenty-Five Years of Research on Saccharomyces boulardii Trophic Effects: Updates and Perspectives

Abstract

Saccharomyces boulardii (S. boulardii) was discovered by Henri Boulard in 1920 in Indochina. Since then, lyophilized preparations of S. boulardii have increasingly been used throughout the world, providing empirical evidence of its efficacy as an adjuvant agent to treat diarrhea and prevent antibiotic-associated complications. Since 1982, the year of the first publication [1], increasing numbers of studies have been conducted each year to determine the mechanism(s) of action of S. boulardii and to evaluate whether it has beneficial properties for the host organism. More recently, placebo-controlled, double-blind studies have demonstrated the efficacy of S. boulardii as a probiotic medication and as a biotherapeutic agent in some intestinal disorders in both children and adults. The target intestinal disorders are listen in Table 1 along with the corresponding references [2–28]. The references listed here were selected from the MEDLINE database (NIH, National Library) from among 247 publications, including both clinical and experimental studies. The number of publications on S. boulardii has increased since the mid-1990s, now reaching 15 publications per year, while very recently meta-analyses have demonstrated the beneficial effects of S. boulardii treatment, mainly in Clostridium difficileassociated disease, antibiotic-associated diarrheas, and acute infectious diarrheas. Saccharomyces boulardii is a nonpathogenic yeast widely prescribed in a lyophilized form in many countries of the world and used as a biotherapeutical agent [30–32]. The objective of the present report is to provide an update on the intestinal trophic properties of S. boulardii in endoluminal fluid and in intestinal cells at a molecular level. Several authors, using different methods of molecular biology, have shown [33–35] that S. boulardii strains are clustered within the species of S. cerevisiae, the latter having no probiotic effect. The taxonomic position of S. boulardii was evaluated by sequence analysis of the D1/D2 domain of 26S rDNA, the ITS1-5.8S rDNA-ITS2 region, and the mitochondrial cytochrome-c oxidase II gene [36]. The trophic effects of S. boulardii on human and on rat small-intestinal cells have been studied since 1986 [37] and show that oral administration of the lyophilized preparation of the yeast results in a stimulation of human and rat brush border membrane (BBM) enzymes including lactase, sucrase-isomaltase, maltase glucoamylase [37], and a,atrehalase. Incorporation of C-glucosamine into lactase precursor was stimulated by S. boulardii cells whether cells were viable or killed by heating [37]. In addition, oral therapy enhanced the intestinal synthesis of the receptor for polymeric immunoglobulins and the secretion of s-IgA [38] and transporters such as the sodium–glucose cotransporter SGLT1 with increase in glucose uptake by BBM vesicles [39]. Although the precise mechanisms by which yeast cells exert these trophic effects remain unknown there are at least three potential explanations. First, orally given yeast cells secrete directly into the endoluminal fluid enzymes such as sucrase, a,a-trehalase, aminopeptidase [40], and a phosphatase that dephosphorylates very actively the endotoxin of E. coli 55B5, resulting in an inactivation of the toxins by more than 60% as attested by the marked reduction in tissue TNF-a levels and in the absence of liver and cardiac tissue lesions [41]. J.-P. Buts (&) Laboratory of Pediatric Gastroenterology and Nutrition, Faculty of Medicine, Universite Catholique de Louvain, Tour Pasteur +3, 53, Avenue Mounier, 1200 Brussels, Belgium e-mail: buts@gype.ucl.ac.be