Saccharomyces boulardii

Saccharomyces boulardii
Scientific classification
Kingdom:	Fungi
Phylum:	Ascomycota
Subphylum:	Saccharomycotina
Class:	Saccharomycetes
Order:	Saccharomycetales
Family:	Saccharomycetaceae
Genus:	Saccharomyces
Species:	S. boulardii
Binomial name
Saccharomyces boulardii Henri Boulard

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 has been shown to maintain and restore the natural flora in the large and small intestine; it is classified as a probiotic.

Boulard first isolated the 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. S. boulardii has been shown to be non-pathogenic, non-systemic (it remains in the gastrointestinal tract rather than spreading elsewhere in the body), and grows at the unusually high temperature of 37 °C.^[2]

S. boulardii is often marketed as a probiotic in a lyophilized form and is therefore often referred to as Saccharomyces 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.^[3]

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.^[4][5] 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.^[6]

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.^[7]

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.^[8]

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^[9] and benefits to ulcerative colitis patients currently presenting with moderate symptoms.^[10] 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. 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.^[11] The recommended dosage is one 250 mg capsule or sachet per day (QD).

Antibiotic-associated diarrhea

There is evidence for its use in the prophylactic (preventative) treatment of antibiotic-associated diarrhea (AAD) in adults.^[12] There is further evidence for its use to prevent AAD in children.^[13]

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.^[14] 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.^[15]

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.^[16]

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.^[17]

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.^[18]

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. This could aid in the increased recovery rate of a patient from diarrhea.^[19]

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.^[18] 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.^[20]

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.^[21][22] 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.^[23] Secretory IgA provides protection against invading microbes in the gastrointestinal and respiratory tracts.

Human disease

Some cases of fungemia have been reported, especially those with certain digestive disorders, or patients with a central venous catheter. Administration of an antimycotic (antifungal) usually leads to patient recovery from this systemic infection. Patients with yeast allergies are not encouraged to take S. boulardii. S. boulardii has been known to cause disease in immunocompromised humans. In particular, highly concentrated form, marketed as probiotic supplements for the treatment of Clostridium difficile colitis, can possibly cause fungemia in critically ill patients.^[24]

References

1. ^ Malgoire JY, Bertout S, Renaud F, Bastide JM, Mallié M (2005). "Typing of Saccharomyces cerevisiae clinical strains by using microsatellite sequence polymorphism". J. Clin. Microbiol. 43 (3): 1133–7. doi:10.1128/JCM.43.3.1133-1137.2005. PMC 1081240. PMID 15750073. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1081240. 
2. ^ McFarland L, Bernasconi P (1993). "Saccharomyces boulardii: a review of an innovative biotherapeutic agent". Microb Ecol Health Dis 6 (4): 157–71. doi:10.3109/08910609309141323. 
3. ^ Vandenplas Y (July 1999). "Bacteria and yeasts in the treatment of acute and chronic infectious diarrhea. Part II: Yeasts". Clin. Microbiol. Infect. 5 (7): 389–395. doi:10.1111/j.1469-0691.1999.tb00162.x. PMID 11853563. http://www3.interscience.wiley.com/journal/121484705/abstract. 
4. ^ Centina-Sauri G, Sierra Basto G (1994). "Therapeutic evaluation of Saccharomyces boulardii in children with acute diarrhea". Ann Pediatr 41: 397–400. 
5. ^ Kurugöl Z, Koturoğlu G (2005). "Effects of Saccharomyces boulardii in children with acute diarrhoea". Acta Paediatr. 94 (1): 44–7. doi:10.1080/08035250410022521. PMID 15858959. 
6. ^ Höchter W, Chase D, Hagenhoff G (1990). "Saccharomyces boulardii in acute adult diarrhoea. Efficacy and tolerance of treatment". Münch Med Wochenschr 132: 188–92. 
7. ^ McFarland L, Surawicz C, Greenberg R (1994). "A randomised placebo-controlled trial of Saccharomyces boulardii in combination with standard antibiotics for Clostridium difficile disease". J Am Med Assoc 271 (24): 1913–8. doi:10.1001/jama.271.24.1913. PMID 8201735. http://jama.ama-assn.org/cgi/content/abstract/271/24/1913. 
8. ^ Maupas J, Champemont P, Delforge M (1983). "Treatment of irritable bowel syndrome with Saccharomyces boulardii: a double blind, placebo controlled study". Medicine Chirurgie Digestives 12 (1): 77–9. 
9. ^ Guslandi M, Mezzi G, Sorghi M, Testoni PA (2000). "Saccharomyces boulardii in maintenance treatment of Crohn's disease". Dig. Dis. Sci. 45 (7): 1462–4. doi:10.1023/A:1005588911207. PMID 10961730. 
10. ^ Guslandi M, Giollo P, Testoni PA (2003). "A pilot trial of Saccharomyces boulardii in ulcerative colitis". European Journal of Gastroenterology & Hepatology 15 (6): 697–8. PMID 12840682. 
11. ^ Kollaritsch H, Kemsner P, Wiedermann G, Scheiner O (1989). "Prevention of traveler's diarrhoea. Comparison of different non-antibiotic preparations". Travel Med Int: 9–17. 
12. ^ McFarland LV, Surawicz CM, Greenberg RN et al. (1995). "Prevention of beta-lactam-associated diarrhea by Saccharomyces boulardii compared with placebo". Am. J. Gastroenterol. 90 (3): 439–48. PMID 7872284. 
13. ^ Kotowska M, Albrecht P, Szajewska H (2005). "Saccharomyces boulardii in the prevention of antibiotic-associated diarrhoea in children: a randomized double-blind placebo-controlled trial". Aliment. Pharmacol. Ther. 21 (5): 583–90. doi:10.1111/j.1365-2036.2005.02356.x. PMID 15740542. 
14. ^ Saint-Marc T, Blehaut H, Musial C, Touraine J (1995). "AIDS related diarrhea: a double-blind trial of Saccharomyces boulardii". Sem Hôsp Paris 71: 735–41. 
15. ^ Castagliuolo I, Riegler MF, Valenick L, LaMont JT, Pothoulakis C (1999). "Saccharomyces boulardii protease inhibits the effects of Clostridium difficile toxins A and B in human colonic mucosa". Infect. Immun. 67 (1): 302–7. PMC 96311. PMID 9864230. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=96311. 
16. ^ Gedek BR (1999). "Adherence of Escherichia coli serogroup O 157 and the Salmonella typhimurium mutant DT 104 to the surface of Saccharomyces boulardii". Mycoses 42 (4): 261–4. PMID 10424093. 
17. ^ Czerucka D, Rampal P (1999). "Effect of Saccharomyces boulardii on cAMP- and Ca2+ -dependent Cl- secretion in T84 cells". Dig. Dis. Sci. 44 (11): 2359–68. doi:10.1023/A:1026689628136. PMID 10573387. 
18. ^ ^{a b} Dahan S, Dalmasso G, Imbert V, Peyron JF, Rampal P, Czerucka D (2003). "Saccharomyces boulardii interferes with enterohemorrhagic Escherichia coli-induced signaling pathways in T84 cells". Infect. Immun. 71 (2): 766–73. doi:10.1128/IAI.71.2.766-773.2003. PMC 145355. PMID 12540556. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=145355. 
19. ^ Buts JP, De Keyser N, De Raedemaeker L (1994). "Saccharomyces boulardii enhances rat intestinal enzyme expression by endoluminal release of polyamines". Pediatr. Res. 36 (4): 522–7. PMID 7816529. 
20. ^ Thomas S, Przesdzing I, Metzke D, Schmitz J, Radbruch A, Baumgart DC (2009). "Saccharomyces boulardii inhibits lipopolysaccharide-induced activation of human dendritic cells and T cell proliferation". Clin Exp Immunol. 155 (1): 78–87. doi:10.1111/j.1365-2249.2009.03878.x. PMC 2673744. PMID 19161443. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2673744. 
21. ^ Buts JP, Bernasconi P, Van Craynest MP, Maldague P, De Meyer R (1986). "Response of human and rat small intestinal mucosa to oral administration of Saccharomyces boulardii". Pediatr. Res. 20 (2): 192–6. doi:10.1203/00006450-198602000-00020. PMID 3080730. 
22. ^ Zaouche A, Loukil C, De Lagausie P et al. (2000). "Effects of oral Saccharomyces boulardii on bacterial overgrowth, translocation, and intestinal adaptation after small-bowel resection in rats". Scand. J. Gastroenterol. 35 (2): 160–5. doi:10.1080/003655200750024326. PMID 10720113. 
23. ^ Buts JP, Bernasconi P, Vaerman JP, Dive C (1990). "Stimulation of secretory IgA and secretory component of immunoglobulins in small intestine of rats treated with Saccharomyces boulardii". Dig. Dis. Sci. 35 (2): 251–6. doi:10.1007/BF01536771. PMID 2302983. 
24. ^ Muñoz P, Bouza E, Cuenca-Estrella M et al. (2005). "Saccharomyces cerevisiae fungemia: an emerging infectious disease". Clin. Infect. Dis. 40 (11): 1625–34. doi:10.1086/429916. PMID 15889360.