Saccharomyces boulardii

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,[1] S. boulardii is a strain of S. cerevisiae, sharing >99% genomic relatedness, giving the synonym S. cerevisiae var boulardii. A type strain is Hansen CBS 5926.[2][3][4]

Saccharomyces boulardii
Scientific classification
Kingdom: Fungi
Division: Ascomycota
Class: Saccharomycetes
Order: Saccharomycetales
Family: Saccharomycetaceae
Genus: Saccharomyces
Species:
S. boulardii
Binomial name
Saccharomyces boulardii
Seguela, Bastide & Massot

S. boulardii is sometimes used as a probiotic with the purpose of introducing beneficial microbes into the large and small intestines and conferring protection against pathogens.[5][6][7] It grows at 37 °C (98.6 °F).[8] In addition, the popular genome-editing tool CRISPR-Cas9 was proven to be effective in S. boulardii.[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).

Biology

S. boulardii was characterized as a species separate from S. cerevisiae because it does not digest galactose and does not undergo sporulation. Its genomic sequence, however, defines it as a clade under S. cerevisiae, closest to those found in wine. Like S. cerevisiae, it has 16 chromosomes, a 2-micron circle plasmid, and is diploid with genes for both mating types, MATa and MATα. Notably, the MATa locus consistently contains some likely disabling mutations relative to spore-forming S. cerevisiae.[2]

Both S. boulardii and S. cerevisiae produce proteins that inhibit pathogenic bacteria and their toxins, specifically pho8 and ysp3. A yet-unidentified 120 kDa protein also inhibits changes in cAMP levels induced by cholera toxin. S. boulardii encodes extra copies of adhesion proteins that help to stick to pathogenic bacteria and stop them from binding to the intestinal mucus.[2](supp. text)

Medical uses

Antibiotic-associated diarrhea

Evidence exists for its use in the preventive treatment of antibiotic-associated diarrhea (AAD) in adults.[10] Further evidence indicates its use to prevent AAD in children.[11] The potential efficacy of probiotic AAD prevention is dependent on the probiotic strain(s) used and on the dosage.[12][13] A 2015 Cochrane review recommended Lactobacillus rhamnosus or S. boulardii at 5 to 40 billion colony-forming units/day for the prevention of AAD in children, given the modest number needed to treat and the likelihood that adverse events are very rare.[14] A recent meta-analysis of 21 randomised controlled trials (4780 participants) confirmed that S. boulardii is effective in reducing the risk of AAD in children and adults.[15]

Clostridium difficile infection

S. boulardii showed reduction of relapses in some specific patients with recurrent Clostridium difficile infection and may be effective for secondary prevention of C. difficile infection.[16]

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.[17] 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 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.[18]

Blastocystosis

Also, some evidence shows potential benefits of S. boulardii in treatment of blastocystosis.[19][20]

Acute gastroenteritis

A position paper published by ESPGHAN Working Group for Probiotics and Prebiotics based on a systematic reviews and randomized controlled trials suggested that S boulardii (low quality of evidence, strong recommendation) may be considered in the management of children with acute gastroenteritis in addition to rehydration therapy.[21]

Safety

However, in immunocompromised individuals, S. boulardii has been associated with fungemia or localized infection, which may be fatal.[22] 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.[23] A review of HIV-1-infected patients given therapy with S. boulardii indicated it was safe.[24] A retrospective study on 32000 oncohematological hospitalized patients showed no occurrence of fungal sepsis with S. boulardii use.[25]

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): 1133–37. doi:10.1128/JCM.43.3.1133-1137.2005. PMC 1081240. PMID 15750073.
  2. Khatri, Indu; Tomar, Rajul; Ganesan, K.; Prasad, G. S.; Subramanian, Srikrishna (2017-03-23). "Complete genome sequence and comparative genomics of the probiotic yeast Saccharomyces boulardii". Scientific Reports. 7 (1): 371. Bibcode:2017NatSR...7..371K. doi:10.1038/s41598-017-00414-2. ISSN 2045-2322. PMC 5428479. PMID 28336969.
  3. Rajkowska K, Kunicka-Styczyńska A. Phenotypic and Genotypic Characterization of Probiotic Yeasts. Biotechnology & Biotechnological Equipment. 2009; 23 (Suppl 1): 662–65
  4. Łukaszewicz M. Saccharomyces cerevisiae var. boulardii – Probiotic Yeast. Chapter 16. Saccharomyces cerevisiae var. boulardii – Probiotic Yeast. Immunology and Microbiology » "Probiotics", book edited by Everlon Cid Rigobelo, ISBN 978-953-51-0776-7, 2012
  5. Rajkowska, Katarzyna; et al. (April 2012). "Probiotic Activity of Saccharomyces cerevisiae var. boulardii Against Human Pathogens" (PDF). Food Technology and Biotechnology. 50: 230–36. Retrieved 18 January 2014.
  6. Toma, Malda Maija; et al. (June 2005). "Effect of Probiotic Yeast on Genotoxicity" (PDF). Food Technology and Biotechnology. 43: 301–05. Retrieved 18 January 2014.
  7. Soccol, Carlos Ricardo; et al. (June 2010). "The Potential of Probiotics: A Review" (PDF). Food Technology and Biotechnology. 48: 413–34. Retrieved 18 January 2014.
  8. 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.
  9. Liu, Jing-Jing (2016). "Metabolic Engineering of Probiotic Saccharomyces boulardii". Appl Environ Microbiol. 82 (8): 2280–87. doi:10.1128/AEM.00057-16. PMC 4959471. PMID 26850302.
  10. 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.
  11. 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.
  12. Doron SI, Hibberd PL, Gorbach SL (July 2008). "Probiotics for prevention of antibiotic-associated diarrhea". J Clin Gastroenterol. 42 (Suppl 2): S58–63. doi:10.1097/MCG.0b013e3181618ab7. PMID 18542041.CS1 maint: multiple names: authors list (link)
  13. Surawicz CM (July 2008). "Role of probiotics in antibiotic-associated diarrhea, Clostridium difficile-associated diarrhea, and recurrent Clostridium difficile-associated diarrhea". J Clin Gastroenterol. 42 (Suppl 2): S64–70. doi:10.1097/MCG.0b013e3181646d09. PMID 18545161.
  14. Goldenberg, Joshua Z.; Lytvyn, Lyubov; Steurich, Justin; Parkin, Patricia; Mahant, Sanjay; Johnston, Bradley C. (2015-12-22). "Probiotics for the prevention of pediatric antibiotic-associated diarrhea". The Cochrane Database of Systematic Reviews (12): CD004827. doi:10.1002/14651858.CD004827.pub4. ISSN 1469-493X. PMID 26695080.
  15. Szajewska, H; Kołodziej, M (October 2015). "Systematic review with meta-analysis: Saccharomyces boulardii in the prevention of antibiotic-associated diarrhoea". Alimentary Pharmacology & Therapeutics. 42 (7): 793–801. doi:10.1111/apt.13344. PMID 26216624.
  16. Tung, Jennifer M; Dolovich, Lisa R; Lee, Christine H (December 2009). "Prevention of Clostridium difficile infection with Saccharomyces boulardii: A systematic review". Canadian Journal of Gastroenterology. 23 (12): 817–21. doi:10.1155/2009/915847. ISSN 0835-7900. PMC 2805518. PMID 20011734.
  17. 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.
  18. Szajewska H; Horvath A; Kołodziej M (2015). "Systematic review with meta-analysis: Saccharomyces boulardii supplementation and eradication of Helicobacter pylori infection". Alimentary Pharmacology & Therapeutics. 41 (12): 1237–45. doi:10.1111/apt.13214. PMID 25898944.
  19. Roberts, Tamalee; Stark, Damien; Harkness, John; Ellis, John (2014-05-28). "Update on the pathogenic potential and treatment options for Blastocystis sp". Gut Pathogens. 6: 17. doi:10.1186/1757-4749-6-17. ISSN 1757-4749. PMC 4039988. PMID 24883113.
  20. Dinleyici, Ener Cagri; Eren, Makbule; Dogan, Nihal; Reyhanioglu, Serap; Yargic, Zeynel Abidin; Vandenplas, Yvan (2011-03-01). "Clinical efficacy of Saccharomyces boulardii or metronidazole in symptomatic children with Blastocystis hominis infection". Parasitology Research. 108 (3): 541–45. doi:10.1007/s00436-010-2095-4. ISSN 1432-1955. PMID 20922415.
  21. Szajewska, H; Guarino, A; Hojsak, I; Indrio, F; Kolacek, S; Shamir, R; Vandenplas, Y; Weizman, Z; European Society for Pediatric Gastroenterology, Hepatology, and, Nutrition. (April 2014). "Use of probiotics for management of acute gastroenteritis: a position paper by the ESPGHAN Working Group for Probiotics and Prebiotics". Journal of Pediatric Gastroenterology and Nutrition. 58 (4): 531–39. doi:10.1097/MPG.0000000000000320. PMID 24614141.CS1 maint: multiple names: authors list (link)
  22. Santino I; Alari A; Bono S; Teti E; Marangi M; Bernardini A; Magrini L; Di Somma S; Teggi A (2014). "Saccharomyces cerevisiae fungemia, a possible consequence of the treatment of Clostridium difficile colitis with a probioticum". Int J Immunopathol Pharmacol. 27 (1): 143–46. doi:10.1177/039463201402700120. PMID 24674691.
  23. Kelesidis T, Pothoulakis C. Ther Adv Gastroenterol. 2012; 5(2): 111–25
  24. Canani RB, Cucchiara S, Cuomo R, Pace F, Papale F. Saccharomyces boulardii: a summary of the evidence for gastroenterology clinical practice in adults and children. European Review for Medical and Pharmacological Sciences. 2011; 15: 809–22
  25. Sulik-Tyszka, Beata; Snarski, Emilian; Niedźwiedzka, Magda; Augustyniak, Małgorzata; Myhre, Thorvald Nilsen; Kacprzyk, Anna; Swoboda-Kopeć, Ewa; Roszkowska, Marta; Dwilewicz-Trojaczek, Jadwiga (2017-09-25). "Experience with Saccharomyces boulardii Probiotic in Oncohaematological Patients". Probiotics and Antimicrobial Proteins. 10 (2): 350–355. doi:10.1007/s12602-017-9332-4. ISSN 1867-1314. PMC 5973998. PMID 28948565.
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