Saccharomyces boulardii effects on gastrointestinal diseases.

Abstract

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.

Full text

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Saccharomyces Boulardii effects on gastrointestinal diseases 47
Saccharomyces boulardii effects
on gastrointestinal diseases
Galliano Zanello, François Meurens, Mustapha Berri,
and Henri Salmon*
Institut National de la Recherche Agronomique (INRA),
UR1282, Infectiologie Animale et Santé Publique, F-37380,
Nouzilly (Tours), France.
Abstract
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), AIDS-
associated 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. Online journal at http://www.cimb.org

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48 Zanello et al.
1. Effects of Saccharomyces boulardii on gastrointestinal
diseases: Overview in clinical trials
Several clinical trials have been performed to assess the
efficacy of S. boulardii in the prevention and the treatment of
gastrointestinal diseases which induce diarrhoea (Kotowska
et al., 2005; McFarland, 2006; McFarland et al., 1994;
Szajewska et al., 2007). Diarrhoea is defined as frequent
watery stools resulting from impaired fluid and electrolyte
absorption in the intestinal lumen, and is usually caused
by pathogenic micro-organisms (Roy et al., 1995). These
studies revealed the anti-diarrhoeal effects of the yeast
which reduce the duration and the frequency of diarrhoea
after oral administration.
Antibiotic-associated diarrhoea
Antibiotic-associated diarrhoea (AAD) is an acute
inflammation of the intestinal mucosa caused by the
administration of antibiotics and resulting in the disruption
of the intestinal microflora. Clostridium difficile infection
caused 10-20% of AAD and 95% of pseudomembranous
colitis (Katz et al., 1996; Kelly et al., 1994). Other infectious
organisms causing AAD include Clostridium perfringens,
Staphylococcus aureus, Klebsiella oxytoca, Candida
species and Salmonella species (Hogenauer et al., 1998).
The risk factors to develop AAD are multiple: Host factors,
antibiotherapy and exposure to nosocomial pathogens
(Ackermann et al., 2005; McFarland, 1998). Several
meta-analyses were performed to evaluate the efficacy of
probiotics for the prevention of AAD (Cremonini et al., 2002;
D’Souza et al., 2002; McFarland, 2006; Szajewska et al.,
2006). These studies concluded that S. boulardii is effective
in preventing AAD in adults and children. S. boulardii
preventive effect on AAD was evaluated in 269 children with
otitis media and/or respiratory tract infections (Kotowska et
al., 2005). Children received antibiotic treatment plus 250
mg of S. boulardii (experimental group, n = 132) or a placebo
(control group, n = 137) orally and twice a day during the
antibiotherapy. Analyses included data from 246 children
and demonstrated that the prevalence of diarrhoea was
lower in experimental than in placebo groups (8% versus
23%, relative risk: 0.3, 95% confidence interval: 0.2-0.7).
Moreover, in a recent study conducted on 151 hospitalized
patients, the subjects were divided in two groups of 78 and
73 patients which received respectively antibiotics plus
placebo and antibiotics plus S. boulardii twice a day (Can et
al., 2006). The diarrhoea occurrence was investigated and
the presence of Clostridium difficile toxin A in stools was
evaluated by enzyme-linked immuno sorbent assay. The
results showed a decrease in diarrhoea occurrence (1.4%
versus 9% in the placebo group, P < 0.005). In addition,
C. difficile toxin A assay revealed 2 positive stools samples
(2/7) from patients in the placebo group while nothing was
detected in S. boulardii-treated group (0/7) (Can et al.,
2006).
Recurrent Clostridium difficile-associated diseases
Treatment of Clostridium difficile-associated diseases with
metronidazole or vancomycin is effective, but in few patients,
the disease recurs after the antibiotherapy. Several clinical
trials have shown the efficacy of S. boulardii in combination
with antibiotics for treating relapses of diarrhoea and colitis
(McFarland, 2006; McFarland et al., 1994; Surawicz et al.,
2000). In a first randomized placebo-controlled study, 124
patients treated with antibiotics plus S. boulardii (500 mg
twice daily) had a reduction in occurrence of diarrhoea or
colitis (34.6% versus 64.7% relapses in the placebo group,
P = 0.04) (McFarland et al., 1994). Another study conducted
in 170 patients showed the efficacy of S. boulardii (1g/d for
28 days) plus vancomycin (2g/d for 10 days) in the decrease
of recurrence (16.7% versus 50% in the placebo group, P
= 0.05) (Surawicz et al., 2000). This result was significant
only in patients treated with high-dose of vancomycin (2g/d)
and not with lower dose (500mg/d) or metronidazole (1g/d).
A recent meta-analysis (McFarland, 2006) compared the
efficacy of probiotics (S. boulardii, Lactobacillus rhamnosus
GG and probiotics mixtures) in the prevention of AAD and
the treatment of Clostridium difficile-diseases. The authors
concluded that the three types of probiotics significantly
reduced the development of AAD but only S. boulardii was
shown to be effective for Clostridium difficile-associated
diseases.
Traveller’s diarrhoea
Traveller’s diarrhoea is the most frequent disorder
encountered by persons travelling from low risk regions to
developing areas where enteric infection is hyperendemic.
Enterotoxigenic E. coli, Shigella and Salmonella account for
about 80% of acute traveller’s diarrhoea with an identified
pathogen (Sanders and Tribble, 2001). In a placebo
controlled double-bind study, S. boulardii preventive effect
on traveller’s diarrhoea was evaluated on a total of 1016
travellers assigned in 3 groups (Kollaritsch et al., 1993).
The first group received a placebo and the second and
the third groups received S. boulardii (250 and 1000 mg/d,
respectively). Treatment with the yeast has been assumed
5 days before the travel and during the entire trip. The
incidence of diarrhoea was 39.1% in the placebo group,
34.4% in the second group (P = 0.019 versus placebo),
and 28.7% in the third group (P = 0.005). Recently, a meta-
analysis was performed to assess the efficacy of probiotics
in the prevention of traveller’s diarrhoea and concluded
that S. boulardii and a mixture of Lactobacillus acidophilus
plus Bifidobacterium bifidum had a significant efficacy
(McFarland, 2007).
Acute diarrhoea in children
Diarrhoeal diseases are a leading cause of childhood
morbidity and mortality in developing countries. The
aetiology of acute diarrhoea in children includes infections
of the gastrointestinal tract due to bacteria, viruses or
protozoa, intoxications, systemic infections, malabsorption
disorders, nutritional deficiency, allergy and intolerance
to food or drugs (Guandalini, 2000). There are several
randomized placebo-controlled studies showing the efficacy
of S. boulardii in the management and prevention of acute
childhood diarrhoea (Htwe et al., 2008; Szajewska et al.,
2007). A meta-analysis based on 5 randomized-controlled
trials (619 participants) displayed this effect (Szajewska
et al., 2007). Combined data showed that S. boulardii
reduces significantly diarrhoea duration and the risk of
prolonged diarrhoea compared with control. A recent study
conducted in 100 hospitalized children showed that S.
boulardii treatment for 5 days reduces the mean duration
of diarrhoea (3.08 versus 4.68 days in placebo group, P <
0.05), the frequency of stools (on day 2: 54% versus 30%
in placebo group had less than 3 stools/d, P = 0.019) and

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Saccharomyces Boulardii effects on gastrointestinal diseases 49
normalizes stool consistency (on day 3: 76% versus 24% in
placebo group, P = 0.019) (Htwe et al., 2008).
Diarrhoea in patients with total enteral feeding
Diarrhoea is the most frequent complication in enteral tube
feeding (Whelan et al., 2001). Alterations in the colonic
microflora have been identified in patients receiving enteral
tube feeding and these changes may be associated with the
diarrhoea incidence (Schneider et al., 2000). S. boulardii can
be used to prevent these negative alterations and to reduce
the diarrhoea incidence. The preventive effect of S. boulardii
has been assessed in a multicenter, randomized, double-bind
placebo-controlled study (Bleichner et al., 1997). A total of
128 critically ill patients needing enteral nutrition for at least
6 days were included in the study. S. boulardii administrated
at the dose of 2 g/d reduced the mean percentage of days
with diarrhoea (14.2% versus 18.9% in the placebo group,
odds ratio = 0.67, 95%, confidence interval: 0.50-0.90, P =
0.0069). This study confirmed the results obtained in two
previous clinical trials where S. boulardii administration
decreased the length of diarrhoea events (Schlotterer et al.,
1987; Tempe et al., 1983).
AIDS-associated diarrhoea
Acquired immune deficiency syndrome (AIDS) is a viral
infection characterized by immune cell dysfunction and
subsequent immunodeficiency, as well as intestinal disorder
(Kotler et al., 1984). A randomized, double-bind placebo-
controlled study conducted in 35 patients showed that
administration of S. boulardii (3 g/d) for one week decreases
the diarrhoea incidence. After 7 days of treatment, 61% of
patients were diarrhoea-free compared with 12% in the
placebo group (P < 0.002) (Saint-Marc et al., 1991).
Inflammatory bowel diseases
Inflammatory bowel diseases (IBD) are characterized by
a chronic course in which phases of remission of variable
length are interrupted by acute episodes. The two main
subforms are ulcerative colitis and Crohn’s disease.
Intestinal inflammation in ulcerative colitis is primarily limited
to the colon whereas the whole gastrointestinal tract can be
involved in Crohn’s disease (Xavier and Podolsky, 2007). In
IBD, genetically defects result in abnormal mucosal immune
response overacting the microflora and inducing intestinal
inflammation (Strober et al., 2007). In a pilot study conducted
in 20 patients, administration of S. boulardii in addition
of conventional therapy was found superior to placebo in
promoting reduction of bowel movements (Plein and Hotz,
1993). Furthermore, in another clinical trial conducted
in 32 patients, the preventive effect of S. boulardii was
evaluated in relapses of Crohn’s disease (Guslandi et al.,
2000). After six months, patients treated with mesalamine
alone (3 g/d) presented more clinical relapses compared
to patients receiving S. boulardii (1 g/d) plus mesalamine
(2 g/d) (37.5% versus 6.25%, P = 0.04). The same author
evaluated the effectiveness of S. boulardii in the treatment of
ulcerative colitis in 25 patients. Administration of S. boulardii
(750 mg/d) plus mesalamine for 4 weeks resulted in clinical
remission for 68% of patients (Guslandi et al., 2003).
Irritable bowel syndrome
Irritable bowel syndrome (IBS) is a chronic disorder
involving a combination of abdominal pain and change in
bowel habit and bloating. Recent evidence suggests a role
of the microflora in IBS pathogenesis (Parkes et al., 2008).
In a double-blind, placebo-controlled study conducted in 34
patients with predominant episodes of diarrhoea, treatment
with S. boulardii decreased the daily number of stools (P <
0.05) and improved their consistency (P < 0.05) (Maupas
et al., 1983).
Safety of administration
S. boulardii is administrated to patients in a lyophilized
form and the treatment is well tolerated. However, some
rare cases of S. boulardii fungemias have been reported
in patients with an indwelling central venous catheter (de
Llanos et al., 2006; Hennequin et al., 2000; Lherm et al.,
2002). The origin of the fungemia is thought to be either
a digestive tract translocation or a contamination of the
central venous line by the colonized hands of health
workers (Hennequin et al., 2000). This raises the question
of the risk-benefit ratio of S. boulardii in critically ill or
immunocompromised patients. Thus, administration of S.
boulardii should be contraindicated for patients of fragile
health, as well as for patients with central venous catheter
(Herbrecht and Nivoix, 2005).
2. Experimental effects of Saccharomyces boulardii
These effects have been assessed in several studies and
showed that S. boulardii exerts beneficial mechanisms
in animal models displaying IBD as well as in pathogenic
or opportunistic micro-organism infection models such
as Clostridium difficile, Vibrio cholerae, Escherichia
coli, Salmonella enterica subspecies enterica serovar
Typhimurium, Shigella flexneri, Citrobacter rodentium and
Candida albicans (Chen et al., 2006; Czerucka et al., 1994;
Dahan et al., 2003; Dalmasso et al., 2006b; Jawhara and
Poulain, 2007; Mumy et al., 2007; Wu et al., 2008). These
mechanisms include the modification of host cell signalling
pathways implicated in proinflammatory response and in
hydroelectrolytic secretion, the stimulation of host immune
defences, the neutralization of bacterial toxins and the
decrease of bacterial adherence to intestinal epithelial
cells, the maintenance of membrane permeability and the
inhibition of pathogen translocation. Experimental effects of
S. boulardii on diarrhoeal pathogens have been previously
reviewed (Czerucka and Rampal, 2002).
2.1. Anti-inflammatory effects
Several experimental studies showed that S. boulardii
interferes with the host cell signalling pathways and decreases
the expression of inflammation-associated cytokines such
as interleukin 8 (IL-8), IL-6, IL-1β, tumor necrosis factor
alpha (TNF-α) and interferon gamma (IFN-γ) (Dahan et al.,
2003; Dalmasso et al., 2006b; Mumy et al., 2007). These
studies showed that the yeast can reduce inflammation
in blocking nuclear factor-kappa B (NF-κB) (Dahan et al.,
2003; Mumy et al., 2007) and mitogen-activated protein
kinase (MAPK) activation (Chen et al., 2006; Mumy et al.,
2007), in decreasing nitric oxide (NO) production (Girard et
al., 2005), in enhancing peroxisome proliferators-activated
receptor-gamma (PPAR-γ) expression (Lee et al., 2005)
and in moduling T cell migratory behaviour (Dalmasso et
al., 2006a).

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50 Zanello et al.
Inhibition of NF-κB and MAPK activation
During the course of infection, activation of NF-κB and
MAPK in intestinal epithelial cells results in pro-inflammatory
cytokines secretion and intestinal inflammation. Clostridium
difficile-toxin A induces intestinal inflammation, fluid secretion
and mucosal injury (Torres et al., 1990; Triadafilopoulos et
al., 1987; Triadafilopoulos et al., 1989). After stimulation
with toxin A, S. boulardii supernatant (<10 kDa) has
shown to decrease IL-8 secretion in human colonocytes
and extracellular signal-regulated protein kinases 1 and 2
(ERK1/2) activation in both human colonocytes and murine
ileal loops (Chen et al., 2006). In a model of T84 human
colonic cell line, S. boulardii inhibited also the NF-κB and
MAPK signalling pathways in enterohemorrhagic E. coli
(EHEC) infected-T84 cells resulting in the decrease of IL-8
and TNF-α secretion by epithelial cells (Dahan et al., 2003;
Dalmasso et al., 2006b). Furthermore, the decrease of IL-8
secretion was observed in Shigella flexneri infected-T84
cells when the yeast or the yeast conditioned medium were
added to the monolayer culture (Mumy et al., 2007). This
decrease was greater for cells treated with the conditioned
medium. Furthermore, polymorphonuclear leukocytes
(PMN) transepithelial migration is reduced in presence of
the yeast. This result could be explained by the decrease in
IL-8 secretion level since this cytokine has been previously
shown to be chemoattractant for PMN. S. boulardii
decreased also phosphorilation and activation of ERK and
JNK MAP Kinases and decreased the IκB phosphorilation
and degradation during the infection, thereby preventing
NF-κB activation (Mumy et al., 2007). These events are
likely responsible for the decrease in IL-8 secretion and
PMN transmigration. These anti-inflammatory effects were
confirmed in vivo with a model of human fetal colonic tissue
transplanted into severe combined immunodeficiency
(SCID) mice (Mumy et al., 2007). In addition, recent data
showed that the yeast produces a low molecular weight
soluble factor (< 1 kDa) blocking NF-κB activation and NF-
κB-mediated Il-8 gene expression in intestinal epithelial
cells and monocytes (Sougioultzis et al., 2006) (Figure 1).
Decrease of nitric oxide production
In IBD, production of high levels of NO is associated with
inflammatory effects (Dijkstra et al., 1998). NO is released
through conversion of L-arginine to NO and L-citrulline. This
reaction is catalyzed by three isoforms of the nitric oxide
synthase (NOS): Neuronal NOS, endothelial NOS and
inducible NOS (Moncada et al., 1991). The iNOS activity is
up-regulated during immune activation and can result in the
synthesis of high levels of NO. S. boulardii inhibitory effect
in iNOS activity was displayed in the rat castor oil-induced
diarrhoea model (Girard et al., 2005). The citrulline level (a
marker of NO production) was increased in the colon of rats
whereas S. boulardii administration was shown to block this
production (Figure 1). The same effect is reported with the
iNOS inhibitor. These results suggest that iNOS inhibition by
S. boulardii may be beneficial in the treatment of diarrhoea
and/or IBD associated with overproduction of NO (Girard et
al., 2005).
Enhancement of PPAR-γ expression
PPAR-γ is a nuclear receptor expressed by several cell
types including intestinal epithelial cells, dendritic cells (DC),
T and B cells, and can act as a regulator of the inflammation
(Escher et al., 2001; Mansen et al., 1996; Su et al., 1999).
It has been shown that S. boulardii up-regulates PPAR-γ
expression in human colonocytes at both mRNA and protein
levels (Lee et al., 2005). This up-regulation is correlated
with a reduction of the human colon cell response to
proinflammatory cytokines (Lee et al., 2005) (Figure 1). This
anti-inflammatory effect was supported by previous data
showing that PPAR-γ ligands inhibited NF-κB activation and
that TLR4-activated PPAR-γ in epithelium attenuated NF-
κB signalling (Dubuquoy et al., 2003; Genolet et al., 2004).
A recent study showed that PPAR-γ expression in colonic
epithelial cells decreased pro-inflammatory cytokines levels
and protects mice against experimental IBD (Adachi et al.,
2006). Thus, S. boulardii up-regulates PPAR-γ expression
which could be a therapeutic target in IBD.
Modulation of T cell migratory behaviour
In a model of lymphocyte-transferred SCID mice displaying
IBD, S. boulardii administration decreased the production
of IFN-γ and inflammation in the colon (Dalmasso et al.,
2006a). This observation was correlated with a modification
of T cells distribution. Indeed, the number of IFNγ-producing
CD4+ T cells decreased within the colon and there were more
cells in the mesenteric lymph node. S. boulardii appeared to
be involved in the modification of lymph node endothelial
cell adhesiveness and in the recruitment of IFNγ-producing
CD4+ T cells to this location. These result suggested that
S. boulardii administration could have indirectly beneficial
effect in the treatment of IBD (Dalmasso et al., 2006a).
2.2. Immuno-modulatory effects
Among the mechanisms used by probiotics to improve
the host health, one of them is the stimulation of the host
immunity. Several studies demonstrated that S. boulardii
might induce a protective effect in modulating both innate
and adaptive host immunity to respond against pathogen
infection.
Saccharomyces boulardii effect on innate immunity
S. boulardii immunopharmacological effects in healthy
human volunteers have been evaluated and it has been
shown that the yeast triggered the activation of the
complement and the reticuloendothelial systems (Caetano
et al., 1986). In vitro, the yeast activates the complement
and the migration of monocyte and granulocyte (Caetano et
al., 1986). Furthermore, S. boulardii administration to germ-
free mice has shown to enhance the number of Küpffer
cells (Rodrigues et al., 2000). These results indicate that S.
boulardii is able to stimulate the innate immune system.
Saccharomyces boulardii effect on adaptive immunity
S. boulardii oral administration to rats and mice has shown to
stimulate the secretion of immune factors (Buts et al., 1990;
Qamar et al., 2001; Rodrigues et al., 2000). In the duodenal
fluid of rats treated with the yeast, secretory immunoglobulin
A (sIgA) mean concentration was increased by 56.9%
(versus control, P < 0.01) (Buts et al., 1990). Additionally,
the secretory component was significantly increased in the
duodenal fluid (62.8% versus control, P < 0.01) as well as
in villus cells (69% versus control, P < 0.025) and in crypt
cells (80% versus control, P < 0.01) (Buts et al., 1990). The
same effect was reported in mice challenged with C. difficile
toxin A (Qamar et al., 2001). Treatment with S. boulardii