Saccharomyces boulardii

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, 1923 (nom. inval.)
Type strain
Hansen CBS 5926
Synonyms
  • S. cerevisiae var. boulardii

Saccharomyces boulardii is a tropical yeast first isolated from lychee and mangosteen fruit peel in 1923 by French scientist Henri Boulard. Although early reports claimed distinct taxonomic, metabolic, and genetic properties,[1] S. boulardii is genetically a grouping of S. cerevisiae strains, sharing >99% genomic relatedness, giving the synonym S. cerevisiae var. boulardii.[2][3][4]

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. It also tolerates human body temperature, gastric acid, and digestive enzymes better. Despite all these phenotypic differences, its genomic sequence defines it as a clade under S. cerevisiae, closest to those found in wine. Like ordinary S. cerevisiae, it has 16 chromosomes, a 2-micron circle plasmid, and is diploid with genes for both mating types, MATa and MATα. However, the MATa locus contains some likely disabling mutations relative to spore-forming S. cerevisiae.[2]

Both S. boulardii and ordinary S. cerevisiae produce proteins that inhibit pathogenic bacteria and their toxins, specifically 63-kDa phosphatase pho8 (inhibiting E. coli endotoxin) and 54-kDa serine protease ysp3 (hydrolyzing C. difficile toxins A and B). A yet-unidentified 120 kDa protein also inhibits changes in cAMP levels induced by cholera toxin. S. boulardii encodes extra copies of yeast adhesion proteins called flocculins that help to stick to pathogenic bacteria and stop them from binding to the intestinal mucus.[2]: supp. text 

Medical uses

Saccharomyces boulardii
Clinical data
Trade namesDiarSafe, Florastor
ATC code
Legal status
Legal status
  • US: Over-the-counter
  • EU: Rx & OTC [10]
  • CN: Rx & OTC

The best-characterized "type" CBS 5926 strain is also deposited as ATCC 74012 and CNCM I-745.[11] A CNCM I-1049 strain is also used; it is unclear whether it is the same as CBS 5926.[12]

Antibiotic-associated diarrhea

Evidence exists for its use in the preventive treatment of antibiotic-associated diarrhea (AAD) in adults.[13] Further evidence indicates its use to prevent AAD in children.[14] The potential efficacy of probiotic AAD prevention is dependent on the probiotic strain(s) used and on the dosage.[15][16] A 2015 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.[17] Lactobacillus rhamnosus or Saccharomyces boulardii at high doses (more than 5 billion colony-forming units/day) is moderately effective (with no serious side effects) for the prevention of AAD in children and might also reduce the duration of diarrhea.[18]

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.[19]

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.[20] 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.[21]

Blastocystosis

Also, some evidence shows potential benefits of S. boulardii in treatment of blastocystosis.[22][23]

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.[24]

Other uses

Veterinary use

Food and drinks

S. c. var. boulardii is usable in beer brewing, with live yeast remaining in the finished product. It can coexist alongside other S. cerevisiae in mixed starter cultures.[25]

It can be also used for baking, where its ability to deter bacteria translates into inhibition of rope spoilage, a bread defect caused by Bacillus subtilis or B. licheniformis contamination.[26]

Research

S. boulardii has been shown to reduce body weight in an animal model of type 2 diabetes.[27]

Safety

In immunocompromised individuals, S. boulardii has been associated with fungemia or localized infection, which may be fatal.[28] 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.[29] A review of HIV-1-infected patients given therapy with S. boulardii indicated it was safe.[30] A retrospective study on 32,000 oncohematological hospitalized patients showed no occurrence of fungal sepsis with S. boulardii use.[31]

References

  1. ↑ Malgoire JY, Bertout S, Renaud F, Bastide JM, Mallié M (March 2005). "Typing of Saccharomyces cerevisiae clinical strains by using microsatellite sequence polymorphism". Journal of Clinical Microbiology. 43 (3): 1133–7. doi:10.1128/JCM.43.3.1133-1137.2005. PMC 1081240. PMID 15750073.
  2. 1 2 3 Khatri I, Tomar R, Ganesan K, Prasad GS, Subramanian S (March 2017). "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. PMC 5428479. PMID 28336969. [Note on source: The authors assign strain names based on the supplier of the probiotic. Of these suppliers, Biocodex and EDRL both claim to use the CNCM I-745 strain on their website.]
  3. ↑ Rajkowska K, Kunicka-Styczyńska A (January 2009). "Phenotypic and genotypic characterization of probiotic yeasts". Biotechnology & Biotechnological Equipment. 23 (supplement 1): 662–5. doi:10.1080/13102818.2009.10818511. S2CID 84649167.
  4. ↑ Łukaszewicz M (2012). "Chapter 16: Saccharomyces cerevisiae var. boulardii – Probiotic Yeast". In Rigobelo EC (ed.). Probiotics. pp. 385–98. ISBN 978-953-51-0776-7.
  5. ↑ Rajkowska K, Kunicka-Styczyńska A (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 MM, Raipulis J, Kalnina I, Rutkis R (June 2005). "Effect of Probiotic Yeast on Genotoxicity" (PDF). Food Technology and Biotechnology. 43: 301–05. Retrieved 18 January 2014.
  7. ↑ Soccol CR, Vandenberghe LP, Spier MR, Medeiros AB, Yamaguishi CT, Lindner JD, Pandey A, Thomaz-Soccol V (June 2010). "The Potential of Probiotics: A Review" (PDF). Food Technology and Biotechnology. 48: 413–34. Retrieved 18 January 2014.
  8. ↑ McFarland LV, 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 JJ, Kong II, Zhang GC, Jayakody LN, Kim H, Xia PF, et al. (April 2016). "Metabolic Engineering of Probiotic Saccharomyces boulardii". Applied and Environmental Microbiology. 82 (8): 2280–2287. doi:10.1128/AEM.00057-16. PMC 4959471. PMID 26850302.
  10. ↑ "Active substance: Saccharomyces boulardii" (PDF). List of nationally authorised medicinal products. European Medicines Agency. 15 October 2020.
  11. ↑ "Monograph (draft): Saccharomyces cerevisiae CBS 5926". European Medicines Agency. May 2021. Retrieved 7 February 2022.
  12. ↑ "Scientific Opinion on the substantiation of health claims related to Saccharomyces cerevisiae var. boulardii CNCM I‐1079 and defence against pathogenic gastro‐intestinal microorganisms (ID 913, further assessment) pursuant to Article 13(1) of Regulation (EC) No 1924/2006". EFSA Journal. 10 (6). June 2012. doi:10.2903/j.efsa.2012.2717.
  13. ↑ McFarland LV, Surawicz CM, Greenberg RN, Elmer GW, Moyer KA, Melcher SA, et al. (March 1995). "Prevention of beta-lactam-associated diarrhea by Saccharomyces boulardii compared with placebo". The American Journal of Gastroenterology. 90 (3): 439–48. PMID 7872284.
  14. ↑ Kotowska M, Albrecht P, Szajewska H (March 2005). "Saccharomyces boulardii in the prevention of antibiotic-associated diarrhoea in children: a randomized double-blind placebo-controlled trial". Alimentary Pharmacology & Therapeutics. 21 (5): 583–90. doi:10.1111/j.1365-2036.2005.02356.x. PMID 15740542. S2CID 71993441.
  15. ↑ Doron SI, Hibberd PL, Gorbach SL (July 2008). "Probiotics for prevention of antibiotic-associated diarrhea". Journal of Clinical Gastroenterology. 42 Suppl 2 (Suppl 2): S58-63. doi:10.1097/MCG.0b013e3181618ab7. PMID 18542041. S2CID 2070623.
  16. ↑ Surawicz CM (July 2008). "Role of probiotics in antibiotic-associated diarrhea, Clostridium difficile-associated diarrhea, and recurrent Clostridium difficile-associated diarrhea". Journal of Clinical Gastroenterology. 42 Suppl 2 (Suppl 2): S64-70. doi:10.1097/MCG.0b013e3181646d09. PMID 18545161. S2CID 37993276.
  17. ↑ 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. S2CID 45689550.
  18. ↑ Guo Q, Goldenberg JZ, Humphrey C, El Dib R, Johnston BC (30 April 2019). "Probiotics for the prevention of pediatric antibiotic-associated diarrhea". The Cochrane Database of Systematic Reviews. 4: CD004827. doi:10.1002/14651858.CD004827.pub5. PMC 6490796. PMID 31039287.
  19. ↑ Tung JM, Dolovich LR, Lee CH (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. PMC 2805518. PMID 20011734.
  20. ↑ Saint-Marc T, Blehaut H, Musial C, Touraine JL (1995). "AIDS related diarrhea: a double-blind trial of Saccharomyces boulardii". Sem Hôsp Paris. 71: 735–41.
  21. ↑ Szajewska H, Horvath A, Kołodziej M (June 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. S2CID 21440489.
  22. ↑ Roberts T, Stark D, Harkness J, Ellis J (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. PMC 4039988. PMID 24883113.
  23. ↑ Dinleyici EC, Eren M, Dogan N, Reyhanioglu S, Yargic ZA, Vandenplas Y (March 2011). "Clinical efficacy of Saccharomyces boulardii or metronidazole in symptomatic children with Blastocystis hominis infection". Parasitology Research. 108 (3): 541–5. doi:10.1007/s00436-010-2095-4. PMID 20922415. S2CID 13646648.
  24. ↑ Szajewska H, Guarino A, Hojsak I, Indrio F, Kolacek S, Shamir R, et al. (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): 531–9. doi:10.1097/MPG.0000000000000320. PMID 24614141.
  25. ↑ Capece, A; Romaniello, R; Pietrafesa, A; Siesto, G; Pietrafesa, R; Zambuto, M; Romano, P (2 November 2018). "Use of Saccharomyces cerevisiae var. boulardii in co-fermentations with S. cerevisiae for the production of craft beers with potential healthy value-added". International journal of food microbiology. 284: 22–30. doi:10.1016/j.ijfoodmicro.2018.06.028. PMID 29990636.
  26. ↑ ITMO University (27 June 2020). "Food Science: Baking Self-Healing Bread and Brewing Probiotic Beer". SciTechDaily.
  27. ↑ Stenman LK, Burcelin R, Lahtinen S (2015). "Establishing a causal link between gut microbes, body weight gain and glucose metabolism in humans - towards treatment with probiotics". Beneficial Microbes. 7 (1): 11–22. doi:10.3920/BM2015.0069. PMID 26565087.
  28. ↑ Santino I, Alari A, Bono S, Teti E, Marangi M, Bernardini A, et al. (2014). "Saccharomyces cerevisiae fungemia, a possible consequence of the treatment of Clostridium difficile colitis with a probioticum". International Journal of Immunopathology and Pharmacology. 27 (1): 143–6. doi:10.1177/039463201402700120. PMID 24674691. S2CID 22286501.
  29. ↑ Kelesidis T, Pothoulakis C (March 2012). "Efficacy and safety of the probiotic Saccharomyces boulardii for the prevention and therapy of gastrointestinal disorders". Therapeutic Advances in Gastroenterology. 5 (2): 111–25. doi:10.1177/1756283X11428502. PMC 3296087. PMID 22423260.
  30. ↑ Berni Canani R, Cucchiara S, Cuomo R, Pace F, Papale F (July 2011). "Saccharomyces boulardii: a summary of the evidence for gastroenterology clinical practice in adults and children". European Review for Medical and Pharmacological Sciences. 15 (7): 809–22. PMID 21780551.
  31. ↑ Sulik-Tyszka B, Snarski E, Niedźwiedzka M, Augustyniak M, Myhre TN, Kacprzyk A, et al. (June 2018). "Experience with Saccharomyces boulardii Probiotic in Oncohaematological Patients". Probiotics and Antimicrobial Proteins. 10 (2): 350–355. doi:10.1007/s12602-017-9332-4. PMC 5973998. PMID 28948565.
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