Saccharomyces boulardii is a tropical species of yeast first isolated from lychee and mangosteen fruit in 1923 by French scientist Henri Boulard. Although early reports described distinct taxonomic, metabolic, and genetic properties, S. boulardii (synonym: S. cerevisiae var boulardii and Saccharomyces cerevisiae Hansen CBS 5926) is a strain of S. cerevisiae, sharing >99% genomic relatedness. S. boulardii is sometimes used as a probiotic with the purpose of introducing beneficial active cultures into the large and small intestine, as well as conferring protection against pathogenic microorganisms in the host. It grows at 37 °C (98.6 °F). In addition, the popular genome editing tool CRISPR-Cas9 was proven to be effective in S. boulardii. Boulard first isolated this yeast after he observed natives of Southeast Asia chewing on the skin of lychee and mangosteen in an attempt to control the symptoms of cholera. In healthy patients, S. boulardii has been shown to be nonpathogenic and nonsystemic (it remains in the gastrointestinal tract rather than spreading elsewhere in the body).
Irritable bowel syndromeEdit
A prospective placebo-controlled study found patients with diarrhea-predominant irritable bowel syndrome had a significant reduction on the number and consistency of bowel movements.
Another study in 2011 did not find any change in bowel frequency.
Inflammatory bowel diseaseEdit
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.
Austrian vacationers taking S. boulardii traveling around the world were found to have significantly fewer occurrences of travelers' diarrhea than those taking placebo. A meta-analysis of 12 studies from 1977 to 2005 investigating the efficacy of probiotics found them to be safe and effective for the treatment of travelers' diarrhea, having a pooled relative risk of 0.85 with respect to placebo (between 0.79 and 0.91 with 95% confidence). Three of four studies concerning S. boulardii found it to be an effective treatment. 
Evidence exists for its use in the preventative treatment of antibiotic-associated diarrhea (AAD) in adults. Further evidence indicates its use to prevent AAD in children. The potential efficacy of probiotic AAD prevention is dependent on the probiotic strain(s) used and on the dosage. A 2015 Cochrane review recommended Lactobacillus rhamnosus or Saccharomyces boulardii at 5 to 40 billion colony forming units/day for the prevention of antibiotic-associated diarrhea in children given the modest NNT and the likelihood that adverse events are very rare. A recent meta-analysis of twenty-one randomised controlled trials (4780 participants) confirms that S. boulardii is effective in reducing the risk of antibiotic-associated diarrhoea in children and adults.
Clostridium difficile infectionEdit
Saccharomyces boulardii showed reduction of relapses in some specific patients with recurrent Clostridium difficile infection and may be effective for secondary prevention of Clostridium difficile infection.
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. No adverse reactions were observed in these immunocompromised patients.
Elimination of Helicobacter pylori infectionEdit
The addition of S. boulardii to the standard triple medication protocol for elimination of Helicobacter pylori infection showed a significant increase in eradication rates in a meta-analysis, though eradication rates were still not exceptional. The supplement also significantly decreased usual side effects of H. pylori eradication therapy including diarrhea and nausea.
A position paper published by ESPGHAN Working Group for Probiotics and Prebiotics based on a systematic reviewes and randomized controlled trials (RCTs) suggested that Saccharomyces boulardii (low quality of evidence, strong recommendation) may be considered in the management of children with Acute gastroenteritis in addition to rehydration therapy.
Mechanisms of actionEdit
Saccharomyces boulardii is widely used as a ‘yeast against yeast’ strategy to help inhibit the overgrowth of Candida yeasts in the body. The Candida genus of yeasts are natural residents of the human body; however, when conditions are appropriate for their proliferation, they can multiply and cause yeast infections known as Candidiasis (thrush).
Research indicates that S. boulardii secretes capric, caprylic, and caproic acids which inhibit the hyphae formation on the Candida yeast, preventing it from multiplying. It also reduces Candidial adhesion and biofilm formation, again reducing its ability to thrive and grow (Murzyn et al., 2010). A study showed that both S. boulardii, significantly inhibited Candida albicans adhesion to epithelial cell lines. The IL-8 gene expression by C. albicans-infected Caco-2 cells was suppressed by the addition of S. boulardii. These results indicate that S. boulardii affects C. albicans adhesion and reduces cytokine-mediated inflammatory host response. (Murzyn A. et al., 2010)
A prospective, randomised, comparative study was conducted on a total of 181 preterm infants with a gestational age of less than 32 weeks, and a birth weight of less than 3.3lbs. They were randomised into two groups, to receive either S. boulardii or the anti-fungal nystatin. Weekly skin and stool cultures were performed to determine colonisation, and weekly blood cultures taken to check for invasive infections. Two patients had Candida-positive blood cultures in the nystatin group, whereas no evidence of Candida was seen in the probiotic group. Additionally, feeding intolerance and clinical sepsis were significantly lower in the probiotic group than in the nystatin group (Demirel, et al., 2013).
NB: S. boulardii is not always recommended for those under the age of 1. Check with your probiotics supplier before giving to infants.
Further relevant studies: Algin C., et al. (2005), Berg et al., (1993), Berg R. et al., (1993), Ducluzeau, R., (1982), Jawhara, S., (2007), Kumar S. et al., (2013), Krasowska A. et al., (2009), Lherm T. et al., (2002), McFarland L. V., (2010), Tomičić, Z. et al., (2016).
S. boulardii secretes a 54-kDa protease, in vivo, which has been shown to degrade toxins A and B, secreted from C. 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 enterocytesEdit
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.
During an E. coli infection, myosin light chain is phosphorylated leading to the degradation of the tight junctions between intestinal mucosa enterocytes. S. boulardii has been shown to prevent this phosphorylation, leading to a reduction in mucosal permeability, and thus a decrease in the translocation of the pathogenic bacteria.
Polyamines (spermidine and spermine) have been observed to be released from S. boulardii in the rat ileum. Polyamines have been theorized to stimulate the maturation and turnover of small intestine enterocytes.
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. S. 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. A recent study showed that culture of primary human myeloid dendritic cells CD1c+CD11c+CD123- DC (mDC) in the presence of S. boulardii culture supernatant (active component molecular weight < 3 kDa as evaluated by membrane partition chromatography) significantly reduced expression of the co-stimulatory molecules CD40 and CD80 and the dendritic cell mobilization marker CC-chemokine receptor CCR7 (CD197) induced by the prototypical microbial antigen lipopolysaccharide. Moreover, secretion key proinflammatory cytokines like TNF-α and IL-6 were notably reduced, while the secretion of anti-inflammatory IL-10 did increase. Finally, S. boulardii supernatant inhibited the proliferation of naïve T-cells in a mixed lymphocyte reaction with mDC.
Increased levels of disaccharidasesEdit
The trophic effect on enterocytes has been shown to increase levels of disaccharidases such as lactase, sucrase, maltase, glucoamylase, and N-aminopeptidase in the intestinal mucosa of humans and rats. This can lead to the increased breakdown of disaccharides into monosaccharides that can then be absorbed into the bloodstream via enterocytes. 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 responseEdit
However, in immunocompromised individuals, S. boulardii has been associated with fungemia or localized infection, which may be fatal. Overall, S. boulardii is safe for use in otherwise healthy populations and fungemia with S. boulardii has not been reported, to the best of the recent evidences in immunocompetent patients. In HIV-1-infected patients the therapy with Sb resulted to be safe. A retrospective study on 32000 onchohematological hospitalized patients showed no chances of fungal sepsis with Saccharomyces boulardii use.
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