Saccharomyces boulardii (S.b.) is largely used in Western European countries for the treatment of acute infectious enteritis and antibiotic-induced gastrointestinal disorders. To study the mechanisms of the protective effect of S.b. against enteral pathogen infection, we assessed the response of the intestinal secretion of secretory IgA (s-IgA) and of the secretory component of immunoglobulins (SC) to oral administration of high doses (0.5 mg/g body weight, three times per day) of S.b. cells in growing rats. S.b. cells (biological activity: 2.8 x 10(9) viable cells/100 mg) were administered daily by gastric intubation to weanling rats from day 14 until day 22 postpartum. Control groups received either 0.9% saline or ovalbumin following the same schedule. Expressed per milligram of cell protein, SC content was significantly increased in crypt cells isolated from the jejunum (48.5% vs saline controls, P less than 0.05) as it was in the duodenal fluid (62.8% vs saline controls, P less than 0.01) of rats treated with S.b. Oral treatment with S.b. had no effect on the secretion of SC by the liver. In the duodenal fluid of rats treated with S.b. cells, the mean concentration of s-IgA was increased by 56.9% (P less than 0.01) over the concentration of s-IgA measured in saline controls.(ABSTRACT TRUNCATED AT 250 WORDS)

In EBV-infected pediatric liver transplant recipients, use of OKT3 or antithymocyte globulin and high tacrolimus blood levels are risk factors for a significant increase in the incidence of PTLD. An increase in total gamma-globulin level and appearance of mono/oligoclonal immunoglobulin production are the major preliminary signs of the syndrome.

We conclude that high viral load is systematic in patients who underwent primary EBV infection and is indicative of the PTLD risk only if there is low concomitant cellular immune response. Healing from PTLD requires modulation of immunosuppression, and appearance of EBV-TL.

A total of 2.35% of our transplant children present evidence of immune hepatitis after transplantation. Patients do not respond to increasing cyclosporine or tacrolimus levels and require steroid and azathioprine. In view of this specific treatment, systematic screening for "autoimmune" markers is advised in children with liver transplant.

ABSTRACT. To evaluate the response of the small intesAbbreviations tinal mucosa to Saccharomyces boulardii (S.b.), a yeast widely used in some countries as an adjuvant drug with S-b., Saccharomyces boulardii oral antimicrobial therapy, seven healthy adult volunteers BBM, brush border membrane were treated with high dbses of lyophilized S.b. (250 mg four times per day) for 2 wk. A peroral jejunal suction biopsy was performed on days 0 and 1 5 of the study. Compared to the initial biopsy, histological examination of the posttrial biopsy revealed no morphological alteration nor change in villus height or crypt depth. After treatment, the specific activity (per U protein) of sucrase, lactase, and maltase was, respectively, increased by 82% ( p < 0.05) 77% (p < 0.05), and 75% ( p < 0.05) over the basal activity of the enzymes measured on day 0, whereas mucosal protein content remained unchanged. Similar findings were found in the jejunum of adult rats treated for 5 days with either viable or killed S.b. cells. The changes in total enzyme activity (per jejunal segment) paralleled the changes in specific enzyme activity. I n vitro assays on freshly prepared suspensions of S.b. (6.0 x 10' viable cells/ ml) evidenced a high activity for sucrase (mean 2 SE: 8 364 + 1280 U . g . protein-') but no maltase, neutral lactase, acid P-galactosidase, or aminopeptidase activity. To determine whether treatment with S.b. could influence the incorporation rate of neutral lactase into the brush border membrane, 14-day-old sucklings treated either with saline or with S.b. were given intraperitoneally a dose of 20 pCi D-[ll'C] glucosamine 3 hours before sacrifice. Neutral lactase was isolated on SDS-PAGE of purified BBM. The amount of lactase protein eluted from the gel slices was similar in treated rats (mean + SE: 0.026 + 0.003) and in controls (0.021 -C 0.005 mg protein/ml). Expressed per millieram of brush border membrane lactase protein, there was no significant difference in the incorporation rate of labelled glucosamine between treated rats (mean 2 SE: 8 167 + 1 622 dpm.mg protein-') and controls (9 602 + 1 803 dpm.mg protein-'). In conclusion, short-term oral treatment of human volunteers and rats with S.b. is associated with a marked increase in the activity of disaccharidases without morphological alteration of the intestinal mucosa. Our findings do not suggest an effect of S.b. on the incorporation rate of enzymes into the brush border membrane. (Pediatr Res

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...

To evaluate the role of dietary polyamines in maturation of the rat small intestine, spermine was given orally twice daily to suckling pups from day 10 to day 14 postpartum at different doses: 0, 0.2, 0.5, 1, 2.5, and 5 mumol/dose. Compared to saline treated controls, spermine (5 mumol) produced significant increases in mucosal mass parameters (+12 to +57%, P < 0.05), induced prematurely an adult pattern of microvillous enzymes, and enhanced, respectively, by 19- and 3.5-fold (P < 0.01 vs controls) the concentration of the secretory component of p-immunoglobulins in villous and crypt cells. The response of microvillous enzymes (lactase, sucrase, maltase, and aminopeptidase) to spermine was dose-dependent and -specific since oral administration of arginine (5 mumol) or ornithine (5 mumol) was without effect. Intestinal changes were found to be significant (P < 0.05) for doses of spermine exceeding 1 mumol/day, which is in the range of the amount of polyamines provided by solid pellets at weaning (0.4 mumol/g). However, intestinal changes were undetectable at the physiological amounts of polyamines consumed by pups from rat milk during the suckling period (less than 0.3 mumol/day). Consistent with a direct effect of spermine on the intestinal cell, the cytosolic activity of ornithine decarboxylase was depressed by 27-fold (P < 0.005 vs controls) in the jejunum, while inhibition of ornithine decarboxylase by alpha-difluoromethylornithine did markedly decrease but did not suppress the cell response to spermine. Alternately, plasma corticosteronemia, which was virtually absent by day 14 in controls, ranged between 1.4 and 4.6 micrograms/dl in 60% (N = 9) of the spermine-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)

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