Saccharomyces boulardii

Saccharomyces boulardii is a tropical strain of yeast first isolated from lychee and mangosteen fruit in 1923 by French scientist Henri Boulard. It is related to, but distinct from, Saccharomyces cerevisiae in several taxonomic, metabolic, and genetic properties.^[1] 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.^[2][3][4] However, in immunocompromised individuals, S. Boulardii has been associated with (fungemia) or localized infection, which may be fatal. ^{[citation needed]}

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 non-pathogenic, non-systemic (it remains in the gastrointestinal tract rather than spreading elsewhere in the body). It grows at the unusually high temperature of 37°C (98.6°F).^[5]

S. boulardii is often marketed as a probiotic in a lyophilized form and is therefore often referred to as S. boulardii lyo.

Medical uses

There are numerous randomized, double-blind placebo-controlled studies showing the efficacy of S. boulardii in the treatment and prevention of gastrointestinal disorders.^[6]

Acute diarrhea

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.^[7][8] Children over three months are recommended to take two doses of 250 mg a day (BID) 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.^[9]

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.^[10]

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.^[11]

Inflammatory bowel disease

Further benefits to inflammatory bowel disease (IBD) patients have been suggested in the prevention of relapse in Crohn's disease patients currently in remission^[12] and benefits to ulcerative colitis patients currently presenting with moderate symptoms.^[13] The recommended dosage is three 250 mg capsules a day (TID).^{[citation needed]}

Travelers' diarrhea

Austrian vacationers taking S. boulardii traveling around the world were found to have significantly fewer occurrences of travelers' diarrhea than those taking placebo. ^[14] A meta-analysis of twelve 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. ^[15] The recommended dosage is one 250 mg capsule or sachet per day (QD). ^{[citation needed]}

Antibiotic-associated diarrhea

There is evidence for its use in the prophylactic (preventative) treatment of antibiotic-associated diarrhea (AAD) in adults.^[16] There is further evidence for its use to prevent AAD in children.^[17]

HIV/AIDS-associated diarrhea

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.^[18] There were no reported adverse reaction observed in these immunocompromised patients.

Mechanisms of action

Antitoxin effects

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.^[19]

Antimicrobial effects

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.^[20]

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.^[21]

During an E. coli infection, myosin light chain (MLC) 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.^[22]

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.^[23]

Anti-inflammatory effects

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.^[22] 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). A recent study showed that culture of primary human myeloid dendritic cells CD1c+CD11c+CD123- DC (mDC) in the presence of Saccharomyces boulardii culture supernatant (active component molecular weight < 3kDa 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 (LPS). Moreover, secretion key pro-inflammatory cytokines like 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 (MLR) with mDC.^[24]

Increased levels of disaccharidases

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.^[25][26] This can help in the treatment of diarrhoea, 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.^[27]

References