Saccharomyces boulardii is a tropical strain of yeast first isolated from lychee and mangosteen fruit in 1923 by French scientist Henri Boulard. Saccharomyces boulardii is a viable yeast that is genetically different from Baker’s yeast and other yeasts, and does not contain milk products. S. boulardii is a true “biotic” or living organism which has been shown to have beneficial affects by improving intestinal microbalance when administered in adequate amounts. S. boulardii is not part of the naturally occurring gut flora, and is not significantly impacted by antibiotics. In fact, S. boulardii has been shown to be supportive of antibiotic therapy. Oral administration achieves steady state concentrationsin the colon within three days, but does not colonize in the intestinal tract. The organism is typically cleared from the intestinal tract within 2 to 5 days after discontinuation.
MECHANISMS OF ACTION
S. boulardii secretes a 54 kDa protease, in vivo. This protease has been shown to both degrade toxins A and B, secreted from Clostridium difficile, and inhibit their binding to receptors along the brush border. This leads to a reduction in the enterotoxinic and cytotoxic effects of C. difficile infection.
Escherichia coli and Salmonella typhimurium, two pathogenic bacteria often associated with acute infectious diarrhea, were shown to strongly adhere to mannose on the surface of S. boulardii via lectin receptors (adhesins). Once the invading microbe is bound to S. boulardii, it is prevented from attaching to the brush border; it is then eliminated from the body during the next bowel movement.
Trophic effects on enterocytes
The hypersecretion of water and electrolytes (including chloride ions), caused by cholera toxin during a Vibrio cholerae infection, can be reduced significantly with the introduction of S. boulardii. A 120 kDa protease secreted by S. boulardii has been observed to have an effect on enterocytes lining the large and small intestinal tract–inhibiting the stimulation of adenylate cyclase, which led to the reduction in enterocytic cyclic adenosine monophosphate (cAMP) production and chloride secretion.
Interleukin 8 (IL-8) is a proinflammatory cytokine secreted during an E. coli infection in the gut. S. boulardii has been shown to decrease the secretion of IL-8 during an E. coli infection; S. boulardii could have a protective effect in inflammatory bowel disease. Saccharomyces boulardii may exhibit part of its anti-inflammatory potential through modulation of dendritic cell phenotype, function and migration by inhibition of their immune response to bacterial microbial surrogate antigens such as lipopolysaccharide (LPS). Moreover, secretion key pro-inflammatory cytokines like Tissue Necrosis Factor alpha (TNF-α) and IL-6 were notably reduced, while the secretion of anti-inflammatory IL-10 did increase. Finally Saccharomyces boulardii supernatant inhibited the proliferation of naïve T-cells in a mixed lymphocyte reaction.
Increased levels of disaccharidases
This can help in the treatment of diarrhea, as the level of enzymatic activity has diminished and carbohydrate cannot be degraded and absorbed
Increased immune response
S. boulardii induces the secretion of Immunoglobulin A (IgA) in the small intestine of the rat.
Two studies each showed a significant reduction in the symptoms of acute gastroenteritis in children, versus placebo, by measuring frequency of bowel movements and other criteria. Children over three months are recommended to take two doses of 250 mg a day for five days to treat acute diarrhea. Children under three months are recommended to take half a 250 mg capsule or sachet twice daily for five days.
A prospective placebo-controlled study found a significant reduction in symptoms of diarrhea in adults as well taking 250 mg of S. boulardii twice a day for five days or until symptoms are relieved.
Recurrent Clostridium difficile infection
Administration of two 500 mg doses per day of S. boulardii when given with one of two antibiotics (vancomycin or metronidazole) was found to significantly reduce the rate of recurrent Clostridium difficile (pseudomembranous colitis) infection. No significant benefit was found for prevention of an initial episode of Clostridium difficile-associated disease.
Irritable bowel syndrome
A prospective placebo-controlled study found patients with diarrhea predominant irritable bowel syndrome (IBS) had a significant reduction on the number and consistency of bowel movements.
Inflammatory bowel disease
Further benefits to inflammatory bowel disease patients have been suggested in the prevention of relapse in Crohn's disease patients currently in remission and benefits to ulcerative colitis patients currently presenting with moderate symptoms. The recommended dosage is three 250 mg capsules a day.
Austrian vacationers taking S. boulardii traveling around the world were found to have significantly fewer occurrences of travelers' diarrhea than those taking placebo. The more S. boulardii taken in prevention, starting five days before leaving, the higher the reduction in diarrhea reported. The reduction was also found to be dependent upon where the vacationer traveled. The recommended dosage is one 250 mg capsule or sachet per day
There is evidence for its use in the prophylactic (preventative) treatment of antibiotic-associated diarrhea (AAD) in adults. There is further evidence for its use to prevent AAD in children.
S. boulardii has been shown to significantly increase the recovery rate of stage IV AIDS patients suffering from diarrhea versus placebo. On average, patients receiving S. boulardii gained weight while the placebo group lost weight over the 18 month trial. There were no reported adverse reaction observed in these immunocompromised patients.
OTHER ECOLOGICAL EFFECTS
S. boulardii have been found to interact with a variety of microbes within the gastrointestinal tract of the human body and shown inhibitory effects on inflammation causing agents. S. boulardii have been shown to reduce the concentration of diarrhea causing agents and their associated toxins. All types of diarrhea are effectively remedied by S. boulardii including acute diarrhea in adults, children, and infants, chronic diarrhea in AIDS patients, and diarrhea caused by bacterial infections.
S. boulardii has been utilized as a combatant to anti-biotic associated diarrhea, specifically with patients that suffer from Clostridium difficile. C. difficile infection is caused by anti-biotic treatments which eradicate the natural microflora in the lining of the gut causing inflammation to the colon and diarrhea. S. boulardii has been found to replenish a number of microflora in the digestive tract. C. difficile is an anaerobe which produces two toxins (A & B) responsible for nosocomial diarrhea in adults. Studies have found that S. boulardii decreases levels of C. difficile, however the most prominent effect is the reduction in concentration of C. difficile produced toxins, A and B. S. boulardii does so by releasing a 54-kDa protease that proteolytically digests toxin A and B and their brush border membrane receptors. In addition, S. boulardii inhibits C. difficile growth and has the ability to stimulate host mucosal activity to enhance the intestinal mucosal immune response.
S. boulardii is also effective at inhibiting the effects of Cholera, a condition caused by V. cholerae, a microbe which produces toxins that activate adenylate cyclase to stimulate cyclic AMP production, causing diarrhea.
S. boulardii is an effective treatment for patients with inflammatory bowel disease (IBD). IBD is characterized by the common symptoms of abdominal pain, inflammation of the large intestine, disrupted intestinal transit, constipation or diarrhea, dyspepsia, and distension. Most of these symptoms are a result of an imbalance of microflora. S. boulardii treatment have been found to decrease all the symptoms of IBD.
S. boulardii decreases the quantity and severity of lesions developed by the amoeba E. histolylica.
S. boulardii has been found to be an effective instrument in preventing the relapse of patients with Crohn’s Disease who have already achieved remission. Also, S. boulardii have been found to be advantageous in reducing the gastrointestinal symptoms and diarrhea associated with Ulcerative Collitis.
S. boulardii has also been shown to fight giardiasis, a condition caused by the bacteria, Giardia lamblia which coats the interior of the small intestine, cutting off nutrient absorption.
S. boulardii exhibits excellent anti-microbial effects, specifically against the pathogenic bacteria known as E.coli and S. typhi which cause acute infectious diarrhea. The mode of action known as mannose-sensitive adhesion involves the binding of the pathogenic bacteria to specific sites on the surface of S. boulardii by way of lectin receptors. Because of this irreversible adhesion, pathogenic bacteria are kept from invading the brush border of the intestines, and conveniently excreted.
Bacterial enteropathogens such as the ones above are responsible for approximately 80% of all cases of Traveler’s Diarrhea (TD). Not only has S. boulardii proved to be an effective remedy for diarrhea, but studies have shown that consumption of S. boulardii as a preventative measure (taken 5-7 days prior to departure) decreases the risk of diarrhea.
S. boulardii has been found to effectively treat diarrhea associated with viral infections. As mentioned above, the most studied is chronic diarrhea associated with the HIV virus (AIDS). S. boulardii was given to patients with Stage IV AIDS with the establishment of a control group receiving placebos. Dramatic improvements were seen only 18 months later, including an increase in body weight (whereas the condition of patients given placebos continued to deteriorate significantly) and a decrease of gastrointestinal symptoms.
**Each capsule supplies:
Saccharomyces boulardii 235 mg
Each capsule of Saccharomyces boulardii contains a minimum of 4 billion organisms at the time of manufacture
RECOMMENDATION: One (1) capsule one (1) to three (3) times daily as a dietary supplement or as otherwise directed by a healthcare professional.
Contains: 60 Capsules
Product #: 7900
Current Issues Mol Biol 11:47-58
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.
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.
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.
Therap Adv Gastroenterol. 2012 March; 5(2): 111–125. doi: 10.1177/1756283X11428502
Action of Saccharomyces boulardii
A) Antimicrobial activity
1) Inhibition of growth of bacteria and parasites [Chen et al. 2006; Czerucka et al. 1994; Czerucka and Rampal, 2002; Dahan et al. 2003; Dalmasso et al. 2006a; Gedek, 1999a; Rigothier et al. 1994; Rodrigues et al. 1996; Mumy et al. 2008; Wu et al. 2008]
2) Reduction of gut translocation of pathogens [Herek et al. 2004; Geyik et al. 2006]
3) Neutralization of bacterial virulence factors [Buts et al. 1994; Jahn et al. 1996]
4) Suppression of host cell adherence that interferes with bacterial colonization [Czerucka et al. 2000; Rodrigues et al. 1996; Wu et al. 2008]
B) Antitoxin effects
1) Inhibition of toxin receptor binding sites [Buts et al. 2006; Castagliuolo et al. 1996, 1999; Czerucka et al. 2000; Tasteyre et al. 2002; Wu et al. 2008]
2) Stimulation of antibody production against Clostridium difficile toxin A [Brandao et al. 1998; Qamar et al. 2001]
3) Direct proteolysis of the pathogenic toxins/Secretion of enzymatic proteins [Buts et al. 2006; Castagliuolo et al. 1996; Pothoulakis et al. 1993]
a) Produces a serine protease that cleaves C. difficile toxin A [Pothoulakis et al. 1993]
b) Produces 63 kDa phosphatase that destroys the endotoxin of pathogenic Escherichia coli [Buts et al. 2006; Castagliuolo et al. 1996]
c) Produces a 120 kDa protein that reduces the effects of cholera toxin [Czerucka et al. 1994]
C) Cross-talk with normal microbiota
When S. boulardii is given to antibiotic-exposed mice or patients with diarrhea, normal microbiota is re-established rapidly [Buts et al. 1986, 1999, 2006; Buts, 2009; Swidsinski et al. 2008]
TROPHIC ACTION ON THE INTESTINAL MUCOSA
1) Reduces the number of infected cells and stimulates the growth and differentiation of intestinal cells in response to trophic factors [Barc et al. 2008; Swidsinski et al. 2008]
2) Prevents apoptosis and synthesis of TNFα [Czerucka et al. 2000; Dahan et al. 2003; Dalmasso et al. 2006b]
3) Reduces mucositis [Buts et al. 1986, 1999, 2006; Buts, 2009]
4) Restores fluid transport pathways [Schneider et al. 2005]
5) Stimulates protein and energy production and restores metabolic activities in colonic epithelial cells [Czerucka et al. 2007; Szajewska et al. 2007; Zanello et al. 2009]
6) Secretes mitogenic factors that enhance cell restitution [Canonici et al. 2011]
7) Enhances release of brush-border membrane enzymes [Buts et al. 1998, 2002; Schneider et al. 2005]
8) Stimulates the production of glycoproteins in the brush border [Buts et al. 1990]
9) Stimulates production of intestinal polyamines [Buts et al. 1986, 1994, 1999, 2002; Jahn et al. 1996; Schneider et al. 2005]
10) Restores normal levels of colonic short chain fatty acids (SCFAs) [Buts et al. 1994; Sezer et al. 2009; Breves et al. 2000]
11) Stabilizes gastrointestinal barrier function and strengthens enterocyte tight junctions [Czerucka et al. 2007; Dahan et al. 2003; Szajewska et al. 2007; Wu et al. 2008; Zanello et al. 2009]
12) Reduces crypt hyperplasia and cell damage in colitis models [Wu et al. 2008]
13) Decreases intestinal permeability in Crohn’s disease patients [Garcia et al. 2008]
REGULATION OF THE IMMUNE RESPONSE
A) By acting as an immune stimulant
S. boulardii effects on innate immunity
1) Triggers activation of complement and migration of monocytes and granulocytes [Caetano et al. 1986]
2) Enhances the number of Küpffer cells in germ-free mice [Rodrigues et al. 2000]
S. boulardii effects on adaptive immunity
1) Enhances the mucosal immune response and secretory IgA intestinal levels [Buts et al. 1990; Czerucka et al. 2007; Generoso et al. 2011; Szajewska et al. 2007; Zanello et al. 2009]
2) Enhances systemic immune response and levels of serum IgG to C. difficile toxins A and B. [Czerucka et al. 2007; Qamar et al. 2001]
3) Contributes to earlier production of IFN-γ and IL-12 [Rodrigues et al. 2000; Thomas et al. 2009]
4) Stimulates regulatory T cells [Jahn et al. 1996]
5) Inhibits dendritic cell-induced activation of T cells [Dalmasso et al. 2006a]
6) Modifies migration of lymphocytes in a chronic inflammatory bowel disease model [Dalmasso et al. 2006a]
7) Modifies lymphocyte adherence to endothelial cells, improves cell rolling and adhesion [Dalmasso et al. 2006a]
B) By reducing pro-inflammatory responses and promoting mucosal anti-inflammatory signaling effects
1) Decreases expression of pro-inflammatory cytokines (IL-8, IL-6, IL-1β, TNF-α and IFN-γ) [Dahan et al. 2003; Dalmasso et al. 2006a, 2006b; Mumy et al. 2008; Sougioultzis et al. 2006]
2) Increases expression of the anti-inflammatory cytokine IL-10 [Generoso et al. 2011]
3) Interferes with NF-κB-mediated signal transduction pathways, in immune and colonic epithelial cells [Buts, 2009; Dahan et al. 2003; Mumy et al. 2008; Pant et al. 2007; Sougioultzis et al. 2006]
4) Blocks activation of ERK1/2 and MAP kinases [Chen et al. 2006; Kyne et al. 2001; Mumy et al. 2008; Sougioultzis et al. 2006]
5) Decreases NO and inhibits production of inducible NOS [Girard et al. 2005]
6) Modulates T cell migratory behavior and increases trapping of T helper cells into mesenteric lymph nodes [Dalmasso et al. 2006a; Fidan et al. 2009; Sougioultzis et al. 2006; Thomas et al. 2009]
7) Stimulates production of anti-inflammatory molecules in human colonocytes such as PPAR-γ [Chen et al. 2006; Lee et al. 2005, 2009; Mumy et al. 2008]