Saccharomyces boulardii is a yeast widely used in humans for the prevention and treatment of infectious enteritis and Clostridium difficile-associated enterocolopathies. After oral administration to human volunteers or growing rats, S. boulardii enhances markedly the expression of intestinal enzymes as well as the production of the polymeric immunoglobulin receptor by mechanisms that remain unknown. We have analyzed the role of the yeast polyamines as potential mediators in the intestinal trophic response. In weanling rats (d 20 to d 30), a daily dose of 100 mg of lyophilized S. boulardii produced significant (p < 0.025) increases in sucrase (157%) and maltase (47%) activities. This dose corresponded to a total oral load of 678 nmol of polyamines per day (spermidine: 376 + 32, spermine: 293 + 26, putrescine: 9.5 + 1.4 nmo11100 mg). Spermine, given orally to growing rats at doses nearly equivaSaccharomyces boulardii is a thermophilic, nontoxic yeast used in many countries for the treatment of acute infectious enteritis (I), antibiotic-induced gastrointestinal disorders (2, 3), and Clostridium dificile-associatedenterocolopathies (4, 5). The physiologic impact of the yeast on the gastrointestinal tract of mammals remains largely unknown. In a previous study (6), we have shown that the oral treatment of human volunteers and weaned rats with a lyophilized preparation of S. boulardii resulted in marked increases in the specific and total activities of brush-border membrane enzymes without morphologic alteration of the intestinal mucosa.Subsequently, w e found increased secretion of IgA and of the polymeric immunoglobulin receptor in intestinal fluid and mucosa of rats treated with S. boulardii (7). Although these changes may contribute to the explana- lent (500 nmol) to the load of polyamines provided by the yeast (678 nmol), reproduced similar enzymatic changes, including a 2.5-fold induction of sucrase, and enhanced maltase activity (+24%). Spermidine and spermine concentrations measured in the jejunal mucosa of treated rats were increased over matched controls by 21.4% (p < 0.005) and 21.9%, respectively (p < 0.002). After being centrifuged and filtered to discard residual yeast cells, 2-mL samples of jejunal and ileal fluid collected from S. boulardii-treated rats by intestinal flushing contained higher levels of spermidine (48 and 60%) and spermine (150 and 316%) than did control rats. Our data indicate that lyophilized S. boulardii exerts trophic effects on the small intestine that are likely mediated by the endoluminal release of spermine and spermidine. (Pediufr Res 36: 522-527, 1994) tion of the beneficial effects of the yeast therapy in certain intestinal disorders, the exact mechanism by which S. boulardii exerts trophic effects on the small intestinal mucosa is not elucidated. Preliminary findings (6, 7) indicate that the enhanced expression of surface membrane glycoproteins including disaccharidases and secretory component seems unrelated to an increase in cell turnover (7) or to changes in the incorp...

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Saccharomyces boulardii (S. boulardii) is a non-pathogenic biotherapeutic agent, widely prescribed in a lyophilized form in many countries over the world. S. boulardii acts as a shuttle liberating effective enzymes, proteins and trophic factors during its intestinal transit that improve host immune defenses, digestion, and absorption of nutrients. In addition, S. boulardii secretes during its intestinal transit polyamines, mainly spermine and spermidine that regulate gene expression and protein synthesis. In this review, we will focus on the interactions of the yeast with the host intestinal mucosa.

Background-Saccharomyces boulardii is a non-pathogenic yeast which exerts trophic eVects on human and rat small intestinal mucosa. Aims-To examine the eVects of S boulardii on ileal adaptation after proximal enterectomy in rats. Methods-Wistar rats, aged eight weeks, underwent 60% proximal resection or transection and received by orogastric intubation either 1 mg/g body wt per day lyophilised S boulardii or the vehicle for seven days. The eVects on ileal mucosal adaptation were assessed eight days after surgery. Results-Compared with transection, resection resulted in mucosal hyperplasia with significant decreases in the specific and total activities of sucrase, lactase, and maltase. Treatment of resected animals with S boulardii had no eVect on mucosal hyperplasia but did upgrade disaccharidase activities to the levels of the transected group. Enzyme stimulation by S boulardii was associated with significant increases in diamine oxidase activity and mucosal polyamine concentrations. Likewise, sodium dependent D-glucose uptake by brush border membrane vesicles, measured as a function of time and glucose concentration in the incubation medium, was significantly (p<0.05) increased by 81% and three times respectively in the resected group treated with S boulardii. In agreement with this, expression of the sodium/glucose cotransporter-1 in brush border membranes of resected rats treated with S boulardii was enhanced twofold compared with resected controls. Conclusion-Oral administration of S boulardii soon after proximal enterectomy improves functional adaptation of the remnant ileum. (Gut 1999;45:89-96)

The postreceptor events regulating the signal of insulin downstream in rat intestinal cells have not yet been analyzed. Our objectives were to identify the nature of receptor substrates and phosphorylated proteins involved in the signaling of insulin and to investigate the mechanism(s) by which insulin enhances intestinal hydrolases. In response to insulin, the following proteins were rapidly phosphorylated on tyrosine residues: 1) insulin receptor substrates-1 (IRS-1), -2, and -4; 2) phospholipase C-isoenzyme-gamma; 3) the Ras-GTPase-activating protein (GAP) associated with Rho GAP and p62(Src); 4) the insulin receptor beta-subunit; 5) the p85 subunits of phosphatidylinositol 3-kinase (PI 3-kinase); 6) the Src homology 2 alpha-collagen protein; 7) protein kinase B; 8) mitogen-activated protein (MAP) kinase-1 and -2; and 9) growth receptor-bound protein-2. Compared with controls, insulin enhanced the intestinal activity of MAP kinase-2 and protein kinase B by two- and fivefold, respectively, but did not enhance p70/S6 ribosomal kinase. Administration of an antireceptor antibody or MAP-kinase inhibitor PD-98059 but not a PI 3-kinase inhibitor (wortmannin) to sucklings inhibited the effects of insulin on mucosal mass and enzyme expression. We conclude that normal rat enterocytes express all of the receptor substrates and mediators involved in different insulin signaling pathways and that receptor binding initiates a signal enhancing brush-border membrane hydrolase, which appears to be regulated by the cascade of MAP kinases but not by PI 3-kinase.