{{Short description|Species of fungus}} {{Speciesbox | image =Saccharomyces-boulardii-Modifies-Salmonella-Typhimurium-Traffic-and-Host-Immune-Responses-along-the-pone.0103069.s011.ogv | image_caption = | genus = Saccharomyces | species = boulardii | authority = 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 [[Taxonomy (biology)|taxonomic]], metabolic, and genetic properties,{{cite journal | vauthors = Malgoire JY, Bertout S, Renaud F, Bastide JM, Mallié M | title = Typing of Saccharomyces cerevisiae clinical strains by using microsatellite sequence polymorphism | journal = Journal of Clinical Microbiology | volume = 43 | issue = 3 | pages = 1133–1137 | date = March 2005 | pmid = 15750073 | pmc = 1081240 | doi = 10.1128/JCM.43.3.1133-1137.2005 }} ''S. boulardii'' is genetically a grouping of ''[[S. cerevisiae]]'' strains, sharing >99% genomic relatedness, giving the synonym '''''S. cerevisiae'' var. ''boulardii'''''.{{cite journal | vauthors = Khatri I, Tomar R, Ganesan K, Prasad GS, Subramanian S | title = Complete genome sequence and comparative genomics of the probiotic yeast Saccharomyces boulardii | journal = Scientific Reports | volume = 7 | issue = 1 | pages = 371 | date = March 2017 | pmid = 28336969 | pmc = 5428479 | doi = 10.1038/s41598-017-00414-2 | bibcode = 2017NatSR...7..371K }} [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.]{{cite journal | vauthors = Rajkowska K, Kunicka-Styczyńska A | title = Phenotypic and genotypic characterization of probiotic yeasts. | journal = Biotechnology & Biotechnological Equipment | date = January 2009 | volume = 23 | issue = supplement 1 | pages = 662–5 | doi = 10.1080/13102818.2009.10818511 | s2cid = 84649167 | doi-access = free }}{{cite book | vauthors = Łukaszewicz M | chapter = Chapter 16: Saccharomyces cerevisiae var. boulardii – Probiotic Yeast | pages = 385–98 | veditors = Rigobelo EC | title = Probiotics | isbn = 978-953-51-0776-7 | date = 2012 }}
''S. boulardii'' is sometimes used as a [[probiotic]] with the purpose of introducing beneficial microbes into the large and small [[intestine]]s and conferring protection against pathogens.{{cite journal|vauthors=Rajkowska K, Kunicka-Styczyńska A|title=Probiotic Activity of Saccharomyces cerevisiae var. boulardii Against Human Pathogens|journal=Food Technology and Biotechnology|date=April 2012|volume=50|pages=230–36|url=http://www.ftb.com.hr/images/pdfarticles/2012/April-June/230.pdf|access-date=18 January 2014|archive-date=9 March 2021|archive-url=https://web.archive.org/web/20210309162314/http://www.ftb.com.hr/images/pdfarticles/2012/April-June/230.pdf|url-status=live}}{{cite journal|vauthors=Toma MM, Raipulis J, Kalnina I, Rutkis R|title=Effect of Probiotic Yeast on Genotoxicity|journal=Food Technology and Biotechnology|date=June 2005|volume=43|pages=301–05|url=http://www.ftb.com.hr/images/pdfarticles/2005/July-September/43-301.pdf|access-date=18 January 2014|archive-date=2 December 2020|archive-url=https://web.archive.org/web/20201202083246/http://www.ftb.com.hr/images/pdfarticles/2005/July-September/43-301.pdf|url-status=live}}{{cite journal|vauthors=Soccol CR, Vandenberghe LP, Spier MR, Medeiros AB, Yamaguishi CT, Lindner JD, Pandey A, Thomaz-Soccol V|title=The Potential of Probiotics: A Review|journal=Food Technology and Biotechnology|date=June 2010|volume=48|pages=413–34|url=http://www.ftb.com.hr/images/pdfarticles/2010/October-December/ftb_48_413.pdf|access-date=18 January 2014|archive-date=2 December 2020|archive-url=https://web.archive.org/web/20201202090201/http://www.ftb.com.hr/images/pdfarticles/2010/October-December/ftb_48_413.pdf|url-status=live}} It grows at 37 °C (98.6 °F).{{cite journal | title=''Saccharomyces boulardii'': a review of an innovative biotherapeutic agent | vauthors = McFarland LV, Bernasconi P | journal=Microb Ecol Health Dis | year=1993 | volume=6 | pages=157–71 | doi=10.3109/08910609309141323 | issue=4| doi-access=free }} In addition, the popular genome-editing tool [[CRISPR gene editing|CRISPR-Cas9]] was proven to be effective in ''S. boulardii''.{{cite journal | vauthors = Liu JJ, Kong II, Zhang GC, Jayakody LN, Kim H, Xia PF, Kwak S, Sung BH, Sohn JH, Walukiewicz HE, Rao CV, Jin YS | display-authors = 6 | title = Metabolic Engineering of Probiotic Saccharomyces boulardii | journal = Applied and Environmental Microbiology | volume = 82 | issue = 8 | pages = 2280–2287 | date = April 2016 | pmid = 26850302 | pmc = 4959471 | doi = 10.1128/AEM.00057-16 | bibcode = 2016ApEnM..82.2280L }} 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 people, ''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, [[mating of yeast|MATa and MATα]]. However, the MATa locus contains some likely disabling mutations relative to spore-forming ''S. cerevisiae''.
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 [[Clostridium difficile toxin A|''C. difficile'' toxins A]] and [[Clostridium difficile toxin B|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 [[yeast flocculation|flocculin]]s that help to stick to pathogenic bacteria and stop them from binding to the intestinal mucus.{{rp|at=supp. text}}
==Medical uses== {{Infobox drug | drug_name = | INN = | type = | image = | width = | alt = | caption =
| pronounce = | tradename = DiarSafe, Florastor | Drugs.com = | MedlinePlus = | licence_CA = | licence_EU = | DailyMedID = | licence_US = | pregnancy_AU = | pregnancy_AU_comment = | pregnancy_US = | pregnancy_US_comment = | pregnancy_category= | routes_of_administration = | class = | ATCvet = | ATC_prefix = A07 | ATC_suffix = FA02 | ATC_supplemental =
| legal_AU = | legal_AU_comment = | legal_BR = | legal_BR_comment = | legal_CA = | legal_CA_comment = | legal_DE = | legal_DE_comment = | legal_NZ = | legal_NZ_comment = | legal_UK = | legal_UK_comment = | legal_US = Over-the-counter | legal_US_comment = | legal_EU = Rx & OTC | legal_EU_comment = {{cite web | title = Active substance: Saccharomyces boulardii | series = List of nationally authorised medicinal products | url = https://www.ema.europa.eu/documents/psusa/saccharomyces-boulardii-list-nationally-authorised-medicinal-products-psusa/00009284/202002_en.pdf | publisher = European Medicines Agency | date = 15 October 2020 | access-date = 4 December 2020 | archive-date = 30 June 2024 | archive-url = https://web.archive.org/web/20240630090201/https://www.ema.europa.eu/documents/psusa/saccharomyces-boulardii-list-nationally-authorised-medicinal-products-psusa/00009284/202002_en.pdf | url-status = live }} | legal_UN = | legal_UN_comment = | legal_status = CN: Rx & OTC
| bioavailability = | protein_bound = | metabolism = | metabolites = | onset = | elimination_half-life = | duration_of_action = | excretion =
| CAS_number_Ref = | CAS_number = | CAS_supplemental = | PubChem = | IUPHAR_ligand = | DrugBank_Ref = | DrugBank = | ChemSpiderID_Ref = | ChemSpiderID = | UNII_Ref = | UNII = | KEGG_Ref = | KEGG = | KEGG2_Ref = | KEGG2 = | ChEBI_Ref = | ChEBI = | ChEMBL_Ref = | ChEMBL = | NIAID_ChemDB = | PDB_ligand = | synonyms =
| IUPAC_name = | chemical_formula_ref = | chemical_formula = | C= | H= | Ag= | Al= | As= | Au= | B= | Bi= | Br= | Ca= | Cl= | Co= | F= | Fe= | Gd= | I= | K= | Li= | Mg= | Mn= | N= | Na= | O= | P= | Pt= | S= | Sb= | Se= | Sr= | Tc= | Zn= | charge= | molecular_weight = | molecular_weight_comment = | SMILES = | StdInChI = | StdInChI_comment = | StdInChIKey = | density = | density_notes = | melting_point = | melting_high = | melting_notes = | boiling_point = | boiling_notes = | solubility = | sol_units = | specific_rotation = }} The best-characterized "type" CBS 5926 strain is also deposited as [[American Type Culture Center|ATCC]] 74012 and [[CNCM]] I-745.{{cite web |title=Monograph (draft): Saccharomyces cerevisiae CBS 5926 |url=https://www.ema.europa.eu/en/medicines/herbal/saccharomyces-cerevisiae-cbs-5926 |website=European Medicines Agency |access-date=7 February 2022 |date=May 2021 |archive-date=7 February 2022 |archive-url=https://web.archive.org/web/20220207105604/https://www.ema.europa.eu/en/medicines/herbal/saccharomyces-cerevisiae-cbs-5926 |url-status=live }} A CNCM I-1049 strain is also used; it is unclear whether it is the same as CBS 5926.{{cite journal |title=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 |journal=EFSA Journal |date=June 2012 |volume=10 |issue=6 |doi=10.2903/j.efsa.2012.2717 |s2cid=89283884 |language=en|doi-access=free }}
=== Antibiotic-associated diarrhea === Evidence exists for its use in the [[prophylactic|preventive]] treatment of [[antibiotic-associated diarrhea]] (AAD) in adults.{{cite journal | vauthors = McFarland LV, Surawicz CM, Greenberg RN, Elmer GW, Moyer KA, Melcher SA, Bowen KE, Cox JL | display-authors = 6 | title = Prevention of beta-lactam-associated diarrhea by Saccharomyces boulardii compared with placebo | journal = The American Journal of Gastroenterology | volume = 90 | issue = 3 | pages = 439–448 | date = March 1995 | pmid = 7872284 }} Further evidence indicates its use to prevent AAD in children.{{cite journal | vauthors = Kotowska M, Albrecht P, Szajewska H | title = Saccharomyces boulardii in the prevention of antibiotic-associated diarrhoea in children: a randomized double-blind placebo-controlled trial | journal = Alimentary Pharmacology & Therapeutics | volume = 21 | issue = 5 | pages = 583–590 | date = March 2005 | pmid = 15740542 | doi = 10.1111/j.1365-2036.2005.02356.x | s2cid = 71993441 | doi-access = free }} The potential efficacy of probiotic AAD prevention is dependent on the probiotic strain(s) used and on the dosage.{{cite journal | vauthors = Doron SI, Hibberd PL, Gorbach SL | title = Probiotics for prevention of antibiotic-associated diarrhea | journal = Journal of Clinical Gastroenterology | volume = 42 | issue = Suppl 2 | pages = S58–S63 | date = July 2008 | pmid = 18542041 | doi = 10.1097/MCG.0b013e3181618ab7 | s2cid = 2070623 }}{{cite journal | vauthors = Surawicz CM | title = Role of probiotics in antibiotic-associated diarrhea, Clostridium difficile-associated diarrhea, and recurrent Clostridium difficile-associated diarrhea | journal = Journal of Clinical Gastroenterology | volume = 42 | issue = Suppl 2 | pages = S64–S70 | date = July 2008 | pmid = 18545161 | doi = 10.1097/MCG.0b013e3181646d09 | s2cid = 37993276 }} 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.{{cite journal | vauthors = Szajewska H, Kołodziej M | title = Systematic review with meta-analysis: Saccharomyces boulardii in the prevention of antibiotic-associated diarrhoea | journal = Alimentary Pharmacology & Therapeutics | volume = 42 | issue = 7 | pages = 793–801 | date = October 2015 | pmid = 26216624 | doi = 10.1111/apt.13344 | s2cid = 45689550 | doi-access = free }} ''[[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.{{cite journal | vauthors = Guo Q, Goldenberg JZ, Humphrey C, El Dib R, Johnston BC | title = Probiotics for the prevention of pediatric antibiotic-associated diarrhea | journal = The Cochrane Database of Systematic Reviews | volume = 4 | issue = 4 | pages = CD004827 | date = April 2019 | pmid = 31039287 | pmc = 6490796 | doi = 10.1002/14651858.CD004827.pub5 }}
=== ''Clostridium difficile'' infection === ''S. boulardii'' showed reduction of relapses in some specific patients with recurrent [[Clostridium difficile infection|''Clostridium difficile'' infection]] and may be effective for secondary prevention of ''C. difficile'' infection.{{cite journal | vauthors = Tung JM, Dolovich LR, Lee CH | title = Prevention of Clostridium difficile infection with Saccharomyces boulardii: a systematic review | journal = Canadian Journal of Gastroenterology | volume = 23 | issue = 12 | pages = 817–821 | date = December 2009 | pmid = 20011734 | pmc = 2805518 | doi = 10.1155/2009/915847 | doi-access = free }}
=== HIV/AIDS-associated diarrhea === ''S. boulardii'' has been shown to significantly increase the recovery rate of stage IV [[AIDS]] patients with diarrhea versus placebo. On average, patients receiving ''S. boulardii'' gained weight, while the placebo group lost weight over the 18-month trial.{{ cite journal | title=AIDS related diarrhea: a double-blind trial of ''Saccharomyces boulardii'' | journal=Sem Hôsp Paris | year=1995 | volume=71 | pages=735–41 | vauthors = Saint-Marc T, Blehaut H, Musial C, Touraine JL }} No adverse reactions were observed in these [[immunocompromised]] patients.
=== Elimination of ''Helicobacter pylori'' infection === {{See also|Helicobacter pylori eradication protocols}} 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.{{cite journal | vauthors = Szajewska H, Horvath A, Kołodziej M | title = Systematic review with meta-analysis: Saccharomyces boulardii supplementation and eradication of Helicobacter pylori infection | journal = Alimentary Pharmacology & Therapeutics | volume = 41 | issue = 12 | pages = 1237–1245 | date = June 2015 | pmid = 25898944 | doi = 10.1111/apt.13214 | s2cid = 21440489 | doi-access = free }}
=== Blastocystosis === Also, some evidence shows potential benefits of ''S. boulardii'' in treatment of [[blastocystosis]].{{cite journal | vauthors = Roberts T, Stark D, Harkness J, Ellis J | title = Update on the pathogenic potential and treatment options for Blastocystis sp | journal = Gut Pathogens | volume = 6 | pages = 17 | date = 2014-05-28 | pmid = 24883113 | pmc = 4039988 | doi = 10.1186/1757-4749-6-17 | doi-access = free }}{{cite journal | vauthors = Dinleyici EC, Eren M, Dogan N, Reyhanioglu S, Yargic ZA, Vandenplas Y | title = Clinical efficacy of Saccharomyces boulardii or metronidazole in symptomatic children with Blastocystis hominis infection | journal = Parasitology Research | volume = 108 | issue = 3 | pages = 541–545 | date = March 2011 | pmid = 20922415 | doi = 10.1007/s00436-010-2095-4 | s2cid = 13646648 }}
=== 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.{{cite journal | vauthors = Szajewska H, Guarino A, Hojsak I, Indrio F, Kolacek S, Shamir R, Vandenplas Y, Weizman Z | display-authors = 6 | title = Use of probiotics for management of acute gastroenteritis: a position paper by the ESPGHAN Working Group for Probiotics and Prebiotics | journal = Journal of Pediatric Gastroenterology and Nutrition | volume = 58 | issue = 4 | pages = 531–539 | date = April 2014 | pmid = 24614141 | doi = 10.1097/MPG.0000000000000320 | s2cid = 1989479 | doi-access = free }}
== Other uses ==
=== 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.{{cite journal | vauthors = Capece A, Romaniello R, Pietrafesa A, Siesto G, Pietrafesa R, Zambuto M, Romano P | title = Use of Saccharomyces cerevisiae var. boulardii in co-fermentations with S. cerevisiae for the production of craft beers with potential healthy value-added | journal = International Journal of Food Microbiology | volume = 284 | pages = 22–30 | date = November 2018 | pmid = 29990636 | doi = 10.1016/j.ijfoodmicro.2018.06.028 | s2cid = 51615634 }}
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 ''[[Bacillus licheniformis|B. licheniformis]]'' contamination.{{cite web |author1=ITMO University |title=Food Science: Baking Self-Healing Bread and Brewing Probiotic Beer |url=https://scitechdaily.com/food-science-baking-self-healing-bread-and-brewing-probiotic-beer/ |website=SciTechDaily |date=27 June 2020 |access-date=6 February 2022 |archive-date=6 February 2022 |archive-url=https://web.archive.org/web/20220206141920/https://scitechdaily.com/food-science-baking-self-healing-bread-and-brewing-probiotic-beer/ |url-status=live }}
==Research== ''S. boulardii'' has been shown to reduce body weight in an animal model of [[type 2 diabetes]].{{cite journal | vauthors = Stenman LK, Burcelin R, Lahtinen S | title = Establishing a causal link between gut microbes, body weight gain and glucose metabolism in humans - towards treatment with probiotics | journal = Beneficial Microbes | volume = 7 | issue = 1 | pages = 11–22 | date = February 2016 | pmid = 26565087 | doi = 10.3920/BM2015.0069 }}
==Safety== In [[immunocompromised]] individuals, ''S. boulardii'' has been associated with [[fungemia]] or localized infection, which may be [[terminal illness|fatal]].{{cite journal | vauthors = Santino I, Alari A, Bono S, Teti E, Marangi M, Bernardini A, Magrini L, Di Somma S, Teggi A | display-authors = 6 | title = Saccharomyces cerevisiae fungemia, a possible consequence of the treatment of Clostridium difficile colitis with a probioticum | journal = International Journal of Immunopathology and Pharmacology | volume = 27 | issue = 1 | pages = 143–146 | year = 2014 | pmid = 24674691 | doi = 10.1177/039463201402700120 | s2cid = 22286501 | doi-access = free }} 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.{{cite journal | vauthors = Kelesidis T, Pothoulakis C | title = Efficacy and safety of the probiotic Saccharomyces boulardii for the prevention and therapy of gastrointestinal disorders | journal = Therapeutic Advances in Gastroenterology | volume = 5 | issue = 2 | pages = 111–125 | date = March 2012 | pmid = 22423260 | pmc = 3296087 | doi = 10.1177/1756283X11428502 }} A review of HIV-1-infected patients given therapy with ''S. boulardii'' indicated it was safe.{{cite journal | vauthors = Berni Canani R, Cucchiara S, Cuomo R, Pace F, Papale F | title = Saccharomyces boulardii: a summary of the evidence for gastroenterology clinical practice in adults and children | journal = European Review for Medical and Pharmacological Sciences | volume = 15 | issue = 7 | pages = 809–822 | date = July 2011 | pmid = 21780551 }} A retrospective study on 32,000 oncohematological hospitalized patients showed no occurrence of fungal sepsis with ''S. boulardii'' use.{{cite journal | vauthors = Sulik-Tyszka B, Snarski E, Niedźwiedzka M, Augustyniak M, Myhre TN, Kacprzyk A, Swoboda-Kopeć E, Roszkowska M, Dwilewicz-Trojaczek J, Jędrzejczak WW, Wróblewska M | display-authors = 6 | title = Experience with Saccharomyces boulardii Probiotic in Oncohaematological Patients | journal = Probiotics and Antimicrobial Proteins | volume = 10 | issue = 2 | pages = 350–355 | date = June 2018 | pmid = 28948565 | pmc = 5973998 | doi = 10.1007/s12602-017-9332-4 }}
== References == {{Reflist}}
{{Antidiarrheals, intestinal anti-inflammatory and anti-infective agents}} {{Mycoses}} {{Portal bar | Medicine}} {{Taxonbar|from=Q135368}} {{Authority control}}
[[Category:Saccharomyces|boulardii]] [[Category:Yeasts]] [[Category:Probiotics]] [[Category:Fungus species]]