Saccharomyces boulardii

Saccharomyces boulardii is a tropical species of yeast first isolated from lychee and mangosteen fruit in 1923 by French scientist Henri Boulard. Saccharomyces boulardii (synonym: Saccharomyces cervisiae var boulardii and saccharomyces cerevisiae Hansen CBS 5926) is a yeast that could be assigned to the subtype of saccharomyces cerevisiae species.^[1][2] It is related to, but distinct from, Saccharomyces cerevisiae in several taxonomic, metabolic, and genetic properties.^[3] 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.^[4][5][6] However, in immunocompromised individuals, S. boulardii has been associated with fungemia or localized infection, which may be fatal.^[7] 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.^[8] In HIV-1-infected patients the therapy with Sb resulted to be safe.^[9] 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). It grows at 37 °C (98.6 °F).^[10] In addition, it's noteworthy that the popular genome editing tool CRISPR-Cas9 was proven to be effective in S. boulardii.^[11]

Medical uses

Numerous randomized, double-blind, placebo-controlled studies show the efficacy of S. boulardii in the treatment and prevention of gastrointestinal disorders.^[12]

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.^[13][14] 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 taking 250 mg of S. boulardii twice a day for five days or until symptoms are relieved.^[15]

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 C. difficile-associated disease.^[16]

Irritable bowel syndrome

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.^[17]
Another study in 2011 did not find any change in bowel frequency.^[18]

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^[19] and benefits to ulcerative colitis patients currently presenting with moderate symptoms.^[20] The recommended dosage is three 250 mg capsules a day.

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.^[21] 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. ^[22] The recommended dosage is one 250-mg capsule or sachet per day.

Antibiotic-associated diarrhea

Evidence exists for its use in the preventative treatment of antibiotic-associated diarrhea (AAD) in adults.^[23] Further evidence indicates its use to prevent AAD in children.^[24] The potential efficacy of probiotic AAD prevention is dependent on the probiotic strain(s) used and on the dosage.^[25][26] A Cochrane Collaboration systematic review, in which 16 randomized clinical trials (n=3432 participants) were analyzed, concluded that treatments with less than 5000 million CFUs/day did not show a significant decrease of AAD. However, patients treated with ≥5000 million CFUs/day (including L. rhamnosus and Saccharomyces boulardii) had 60% lower relative risk (95%CI: 44–71%) of experiencing AAD than untreated patients.^[27]

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.^[28] No adverse reactions were observed in these immunocompromised patients.

Elimination of Helicobacter pylori infection

The addition of S. Boulardii to the standard triple medication protocol for elimination of H. 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.^[29]

Blastocystosis

There is also evidence showing potential benefits of S. boulardii in treatment of Blastocytosis.^[30][31]

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 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.^[32]

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.^[33]

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.^[34]

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.^[35]

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.^[36]

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.^[35] 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 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 (LPS). 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.^[37]

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.^[38][39] 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 in the small intestine of the rat.^[40]

References