Saccharomyces boulardii

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Saccharomyces boulardii
Scientific classification OOjs UI icon edit-ltr.svg
Domain: Eukaryota
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]

Contents

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 names DiarSafe, 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 Saccharomycesboulardii 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 with 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]

Related Research Articles

<span class="mw-page-title-main">Yeast</span> Informal group of fungi

Yeasts are eukaryotic, single-celled microorganisms classified as members of the fungus kingdom. The first yeast originated hundreds of millions of years ago, and at least 1,500 species are currently recognized. They are estimated to constitute 1% of all described fungal species.

<i>Saccharomyces cerevisiae</i> Species of yeast

Saccharomyces cerevisiae is a species of yeast. The species has been instrumental in winemaking, baking, and brewing since ancient times. It is believed to have been originally isolated from the skin of grapes. It is one of the most intensively studied eukaryotic model organisms in molecular and cell biology, much like Escherichia coli as the model bacterium. It is the microorganism behind the most common type of fermentation. S. cerevisiae cells are round to ovoid, 5–10 μm in diameter. It reproduces by budding.

<i>Clostridioides difficile</i> infection Disease caused by C. difficile bacteria

Clostridioides difficile infection , also known as Clostridium difficile infection, is a symptomatic infection due to the spore-forming bacterium Clostridioides difficile. Symptoms include watery diarrhea, fever, nausea, and abdominal pain. It makes up about 20% of cases of antibiotic-associated diarrhea. Antibiotics can contribute to detrimental changes in gut microbiota; specifically, they decrease short-chain fatty acid absorption which results in osmotic, or watery, diarrhea. Complications may include pseudomembranous colitis, toxic megacolon, perforation of the colon, and sepsis.

<span class="mw-page-title-main">Probiotic</span> Microorganisms said to provide health benefits when consumed

Probiotics are live microorganisms promoted with claims that they provide health benefits when consumed, generally by improving or restoring the gut microbiota. Probiotics are considered generally safe to consume, but may cause bacteria-host interactions and unwanted side effects in rare cases. There is some evidence that probiotics are beneficial for some conditions, but there is little evidence for many of the health benefits claimed for them.

<span class="mw-page-title-main">Fungemia</span> Internal, blood-borne infection by fungi, including yeasts.

Fungemia is the presence of fungi or yeasts in the blood. The most common type, also known as candidemia, candedemia, or systemic candidiasis, is caused by Candida species; candidemia is also among the most common bloodstream infections of any kind. Infections by other fungi, including Saccharomyces, Aspergillus and Cryptococcus, are also called fungemia. It is most commonly seen in immunosuppressed or immunocompromised patients with severe neutropenia, cancer patients, or in patients with intravenous catheters. It has been suggested that otherwise immunocompetent patients taking infliximab may also be at a higher risk for fungemia.

<i>Lacticaseibacillus rhamnosus</i> Species of bacterium

Lacticaseibacillus rhamnosus is a bacterium that originally was considered to be a subspecies of L. casei, but genetic research found it to be a separate species in the L. casei clade, which also includes L. paracasei and L. zeae. It is a short Gram-positive homofermentative facultative anaerobic non-spore-forming rod that often appears in chains. Some strains of L. rhamnosus bacteria are being used as probiotics, and are particularly useful in treating infections of the female urogenital tract, most particularly very difficult to treat cases of bacterial vaginosis. The species Lacticaseibacillus rhamnosus and Limosilactobacillus reuteri are commonly found in the healthy female genito-urinary tract and are helpful to regain control of dysbiotic bacterial overgrowth during an active infection. L. rhamnosus sometimes is used in dairy products such as fermented milk and as non-starter-lactic acid bacterium (NSLAB) in long-ripened cheese. While frequently considered a beneficial organism, L. rhamnosus may not be as beneficial to certain subsets of the population; in rare circumstances, especially those primarily involving weakened immune system or infants, it may cause endocarditis. Despite the rare infections caused by L. rhamnosus, the species is included in the list of bacterial species with qualified presumed safety (QPS) status of the European Food Safety Agency.

<span class="mw-page-title-main">Fecal microbiota transplant</span> Process of transplantation of fecal bacteria from a healthy individual into a recipient

Fecal microbiota transplant (FMT), also known as a stool transplant, is the process of transferring fecal bacteria and other microbes from a healthy individual into another individual. FMT is an effective treatment for Clostridioides difficile infection (CDI). For recurrent CDI, FMT is more effective than vancomycin alone, and may improve the outcome after the first index infection.

<span class="mw-page-title-main">Rifaximin</span> Antibiotic medication

Rifaximin, is a non-absorbable, broad spectrum antibiotic mainly used to treat travelers' diarrhea. It is based on the rifamycin antibiotics family. Since its approval in Italy in 1987, it has been licensed in over more than 30 countries for the treatment of a variety of gastrointestinal diseases like irritable bowel syndrome, and hepatic encephalopathy. It acts by inhibiting RNA synthesis in susceptible bacteria by binding to the RNA polymerase enzyme. This binding blocks translocation, which stops transcription. It is marketed under the brand name Xifaxan by Salix Pharmaceuticals.

Antibiotic-associated diarrhea (AAD) results from an imbalance in the colonic microbiota caused by antibiotics. Microbiotal alteration changes carbohydrate metabolism with decreased short-chain fatty acid absorption and an osmotic diarrhea as a result. Another consequence of antibiotic therapy leading to diarrhea is overgrowth of potentially pathogenic organisms such as Clostridium difficile. It is defined as frequent loose and watery stools with no other complications.

Dysbiosis is characterized by a disruption to the microbiome resulting in an imbalance in the microbiota, changes in their functional composition and metabolic activities, or a shift in their local distribution. For example, a part of the human microbiota such as the skin flora, gut flora, or vaginal flora, can become deranged, with normally dominating species underrepresented and normally outcompeted or contained species increasing to fill the void. Dysbiosis is most commonly reported as a condition in the gastrointestinal tract.

Anti-Saccharomyces cerevisiae antibodies (ASCAs) are antibodies against antigens presented by the cell wall of the yeast Saccharomyces cerevisiae. These antibodies are directed against oligomannose sequences α-1,3 Man n. ASCAs and perinuclear antineutrophil cytoplasmic antibodies (pANCAs) are the two most useful and often discriminating biomarkers for colitis. ASCA tends to recognize Crohn's disease more frequently, whereas pANCA tend to recognize ulcerative colitis.

Helicobacter pylori eradication protocols is a standard name for all treatment protocols for peptic ulcers and gastritis in the presence of Helicobacter pylori infection. The primary goal of the treatment is not only temporary relief of symptoms but also total elimination of H. pylori infection. Patients with active duodenal or gastric ulcers and those with a prior ulcer history should be tested for H. pylori. Appropriate therapy should be given for eradication. Patients with MALT lymphoma should also be tested and treated for H. pylori since eradication of this infection can induce remission in many patients when the tumor is limited to the stomach. Several consensus conferences, including the Maastricht Consensus Report, recommend testing and treating several other groups of patients but there is limited evidence of benefit. This includes patients diagnosed with gastric adenocarcinoma, patients found to have atrophic gastritis or intestinal metaplasia, as well as first-degree relatives of patients with gastric adenocarcinoma since the relatives themselves are at increased risk of gastric cancer partly due to the intrafamilial transmission of H. pylori. To date, it remains controversial whether to test and treat all patients with functional dyspepsia, gastroesophageal reflux disease, or other non-GI disorders as well as asymptomatic individuals.

<i>Clostridium butyricum</i> Species of bacterium

Clostridium butyricum is a strictly anaerobic endospore-forming Gram-positive butyric acid–producing bacillus subsisting by means of fermentation using an intracellularly accumulated amylopectin-like α-polyglucan (granulose) as a substrate. It is uncommonly reported as a human pathogen and is widely used as a probiotic in Asia. C. butyricum is a soil inhabitant in various parts of the world, has been cultured from the stool of healthy children and adults, and is common in soured milk and cheeses. The connection with dairy products is shown by the name, the butyr- in butyricum reflects the relevance of butyric acid in the bacteria's metabolism and the connection with Latin butyrum and Greek βούτυρον, with word roots pertaining to butter and cheese.

<span class="mw-page-title-main">Fidaxomicin</span> Antibiotic

Fidaxomicin, sold under the brand name Dificid among others, is the first member of a class of narrow spectrum macrocyclic antibiotic drugs called tiacumicins. It is a fermentation product obtained from the actinomycete Dactylosporangium aurantiacum subspecies hamdenesis. Fidaxomicin is minimally absorbed into the bloodstream when taken orally, is bactericidal, and selectively eradicates pathogenic Clostridioides difficile with relatively little disruption to the multiple species of bacteria that make up the normal, healthy intestinal microbiota. The maintenance of normal physiological conditions in the colon may reduce the probability of recurrence of Clostridioides difficile infection.

<i>Pediococcus acidilactici</i> Species of bacterium

Pediococcus acidilactici is a species of Gram-positive cocci that is often found in pairs or tetrads. P. acidilactici is a homofermentative bacterium that can grow in a wide range of pH, temperature, and osmotic pressure, therefore being able to colonize the digestive tract. It has emerged as a potential probiotic that has shown promising results in animal and human experiments, though some of the results are limited. They are commonly found in fermented vegetables, fermented dairy products, and meat.

Probiotics are live microorganisms promoted with claims that they provide health benefits when consumed, generally by improving or restoring the gut flora. Probiotics are considered generally safe to consume, but may cause bacteria-host interactions and unwanted side effects in rare cases. There is little evidence that probiotics bring the health benefits claimed for them.

Bacteriotherapy is the purposeful use of bacteria or their products in treating an illness. Forms of bacteriotherapy include the use of probiotics, microorganisms that provide health benefits when consumed; fecal matter transplants (FMT) /intestinal microbiota transplant (IMT), the transfer of gut microorganisms from the fecal matter of healthy donors to recipient patients to restore microbiota; or synbiotics which combine prebiotics, indigestible ingredients that promote growth of beneficial microorganisms, and probiotics. Through these methods, the gut microbiota, the community of 300-500 microorganism species that live in the digestive tract of animals aiding in digestion, energy storage, immune function and protection against pathogens, can be recolonized with favorable bacteria, which in turn has therapeutic effects.

<i>Clostridioides difficile</i> Species of bacteria

Clostridioides difficile is a bacterium known for causing serious diarrheal infections, and may also cause colon cancer. It is known also as C. difficile, or C. diff, and is a Gram-positive species of spore-forming bacteria. Clostridioides spp. are anaerobic, motile bacteria, ubiquitous in nature and especially prevalent in soil. Its vegetative cells are rod-shaped, pleomorphic, and occur in pairs or short chains. Under the microscope, they appear as long, irregular cells with a bulge at their terminal ends. Under Gram staining, C. difficile cells are Gram-positive and show optimum growth on blood agar at human body temperatures in the absence of oxygen. C. difficile is catalase- and superoxide dismutase-negative, and produces up to three types of toxins: enterotoxin A, cytotoxin B and Clostridioides difficile transferase. Under stress conditions, the bacteria produce spores that are able to tolerate extreme conditions that the active bacteria cannot tolerate.

Henri Boulard was a French microbiologist who discovered the yeast Saccharomyces boulardii in 1923. He noticed people chewing on the skins of lychees and mangosteens to treat diarrhea during a cholera epidemic. He isolated and identified this strain of yeast, a probiotic. He sold his patented strain of saccharomyces boulardii to Biocodex, a French pharmaceutical company in the 1950s. This probiotic is used to improve gut health and treat diarrhea and is available in over 100 countries as Florastor.

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): 1133–1137. 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. Bibcode:2016ApEnM..82.2280L. 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 . S2CID   89283884.
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  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): S64–S70. 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 (April 2019). "Probiotics for the prevention of pediatric antibiotic-associated diarrhea". The Cochrane Database of Systematic Reviews. 4 (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): 817–821. 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): 1237–1245. 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): 541–545. 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): 531–539. doi: 10.1097/MPG.0000000000000320 . PMID   24614141. S2CID   1989479.
  25. ↑ Capece A, Romaniello R, Pietrafesa A, Siesto G, Pietrafesa R, Zambuto M, Romano P (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. S2CID   51615634.
  26. ↑ ITMO University (27 June 2020). "Food Science: Baking Self-Healing Bread and Brewing Probiotic Beer". SciTechDaily.
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  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): 143–146. doi: 10.1177/039463201402700120 . PMID   24674691. S2CID   22286501.
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  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): 809–822. 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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