Saccharomyces boulardii
Encyclopedia
Saccharomyces boulardii is a tropical strain of yeast
Yeast
Yeasts are eukaryotic micro-organisms classified in the kingdom Fungi, with 1,500 species currently described estimated to be only 1% of all fungal species. Most reproduce asexually by mitosis, and many do so by an asymmetric division process called budding...

 first isolated from lychee
Lychee
The lychee is the sole member of the genus Litchi in the soapberry family, Sapindaceae. It is a tropical and subtropical fruit tree native to Southern China and Southeast Asia, and now cultivated in many parts of the world...

 and mangosteen
Mangosteen
The purple mangosteen , colloquially known simply as mangosteen, is a tropical evergreen tree believed to have originated in the Sunda Islands and the Moluccas of Indonesia. The tree grows from 7 to 25 m tall...

 fruit in 1923 by French scientist Henri Boulard. It is related to, but distinct from, Saccharomyces cerevisiae
Saccharomyces cerevisiae
Saccharomyces cerevisiae is a species of yeast. It is perhaps the most useful yeast, having been instrumental to baking and brewing since ancient times. It is believed that it was originally isolated from the skin of grapes...

in several taxonomic, metabolic, and genetic properties. S. boulardii has been shown to maintain and restore the natural flora
Gut flora
Gut flora consists of microorganisms that live in the digestive tracts of animals and is the largest reservoir of human flora. In this context, gut is synonymous with intestinal, and flora with microbiota and microflora....

 in the large and small intestine
Intestine
In human anatomy, the intestine is the segment of the alimentary canal extending from the pyloric sphincter of the stomach to the anus and, in humans and other mammals, consists of two segments, the small intestine and the large intestine...

; it is classified as a probiotic
Probiotic
Probiotics are live microorganisms thought to be beneficial to the host organism. According to the currently adopted definition by FAO/WHO, probiotics are: "Live microorganisms which when administered in adequate amounts confer a health benefit on the host"...

.

Boulard first isolated the yeast after he observed natives of Southeast Asia
Southeast Asia
Southeast Asia, South-East Asia, South East Asia or Southeastern Asia is a subregion of Asia, consisting of the countries that are geographically south of China, east of India, west of New Guinea and north of Australia. The region lies on the intersection of geological plates, with heavy seismic...

 chewing on the skin of lychee and mangosteen in an attempt to control the symptoms of cholera
Cholera
Cholera is an infection of the small intestine that is caused by the bacterium Vibrio cholerae. The main symptoms are profuse watery diarrhea and vomiting. Transmission occurs primarily by drinking or eating water or food that has been contaminated by the diarrhea of an infected person or the feces...

. 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.

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
Double-blind
A blind or blinded experiment is a scientific experiment where some of the people involved are prevented from knowing certain information that might lead to conscious or subconscious bias on their part, invalidating the results....

 placebo
Placebo
A placebo is a simulated or otherwise medically ineffectual treatment for a disease or other medical condition intended to deceive the recipient...

-controlled studies showing the efficacy
Efficacy
Efficacy is the capacity to produce an effect. It has different specific meanings in different fields. In medicine, it is the ability of an intervention or drug to reproduce a desired effect in expert hands and under ideal circumstances.- Healthcare :...

 of S. boulardii in the treatment and prevention of gastrointestinal disorders.

Acute diarrhea

Two studies each showed a significant reduction in the symptoms of acute gastroenteritis
Gastroenteritis
Gastroenteritis is marked by severe inflammation of the gastrointestinal tract involving both the stomach and small intestine resulting in acute diarrhea and vomiting. It can be transferred by contact with contaminated food and water...

 in children, versus placebo, by measuring frequency of bowel movements and other criteria. Children over three months are recommended to take two doses of 250 mg a day (BID) for five days to treat acute diarrhea
Diarrhea
Diarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...

. 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.

Recurrent Clostridium difficile infection

Administration of two 500 mg doses per day of S. boulardii when given with one of two antibiotics (vancomycin
Vancomycin
Vancomycin INN is a glycopeptide antibiotic used in the prophylaxis and treatment of infections caused by Gram-positive bacteria. It has traditionally been reserved as a drug of "last resort", used only after treatment with other antibiotics had failed, although the emergence of...

 or metronidazole
Metronidazole
Metronidazole is a nitroimidazole antibiotic medication used particularly for anaerobic bacteria and protozoa. Metronidazole is an antibiotic, amebicide, and antiprotozoal....

) was found to significantly reduce the rate of recurrent Clostridium difficile
Clostridium difficile
Clostridium difficile , also known as "CDF/cdf", or "C...

(pseudomembranous colitis
Pseudomembranous colitis
Pseudomembranous colitis, a cause of antibiotic-associated diarrhea , is an infection of the colon. It is often, but not always, caused by the bacterium Clostridium difficile. Because of this, the informal name C. difficile colitis is also commonly used. The illness is characterized by...

) infection. No significant benefit was found for prevention of an initial episode of Clostridium difficile-associated disease.

Irritable bowel syndrome

A prospective placebo-controlled study found patients with diarrhea predominant irritable bowel syndrome
Irritable bowel syndrome
Irritable bowel syndrome is a diagnosis of exclusion. It is a functional bowel disorder characterized by chronic abdominal pain, discomfort, bloating, and alteration of bowel habits in the absence of any detectable organic cause. In some cases, the symptoms are relieved by bowel movements...

 (IBS) had a significant reduction on the number and consistency of bowel movements.

Inflammatory bowel disease

Further benefits to inflammatory bowel disease
Inflammatory bowel disease
In medicine, inflammatory bowel disease is a group of inflammatory conditions of the colon and small intestine. The major types of IBD are Crohn's disease and ulcerative colitis.-Classification:...

 (IBD) patients have been suggested in the prevention of relapse
Relapse
Relapse, in relation to drug misuse, is resuming the use of a drug or a dependent substance after one or more periods of abstinence. The term is a landmark feature of both substance dependence and substance abuse, which are learned behaviors, and is maintained by neuronal adaptations that mediate...

 in Crohn's disease
Crohn's disease
Crohn's disease, also known as regional enteritis, is a type of inflammatory bowel disease that may affect any part of the gastrointestinal tract from mouth to anus, causing a wide variety of symptoms...

 patients currently in remission and benefits to ulcerative colitis
Ulcerative colitis
Ulcerative colitis is a form of inflammatory bowel disease . Ulcerative colitis is a form of colitis, a disease of the colon , that includes characteristic ulcers, or open sores. The main symptom of active disease is usually constant diarrhea mixed with blood, of gradual onset...

 patients currently presenting with moderate symptoms. The recommended dosage is three 250 mg capsules a day (TID).

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. 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
Antibiotic-associated diarrhea
Antibiotic-associated diarrhea results from an imbalance in the colonic microbiota caused by antibiotic therapy. Microbiota alteration changes carbohydrate metabolism with decreased short-chain fatty acid absorption and an osmotic diarrhea as a result...

 (AAD) in adults. There is further evidence for its use to prevent AAD in children.

HIV/AIDS-associated diarrhea

S. boulardii has been shown to significantly increase the recovery rate of stage IV AIDS
AIDS
Acquired immune deficiency syndrome or acquired immunodeficiency syndrome is a disease of the human immune system caused by the human immunodeficiency virus...

 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. There were no reported adverse reaction observed in these immunocompromised patients.

Antitoxin effects

S. boulardii secretes a 54 kDa
KDA
KDA may refer to:* Karachi Development Authority* Kongsberg Defence & Aerospace* Kotelawala Defence Academy* Kramer Design Associates* Lithium diisopropylamide, KDA is the potassium analogue of lithium diisopropylamideOr kDa may refer to:...

 protease
Protease
A protease is any enzyme that conducts proteolysis, that is, begins protein catabolism by hydrolysis of the peptide bonds that link amino acids together in the polypeptide chain forming the protein....

, in vivo
In vivo
In vivo is experimentation using a whole, living organism as opposed to a partial or dead organism, or an in vitro controlled environment. Animal testing and clinical trials are two forms of in vivo research...

. 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
Brush border
A brush border is the name for the microvilli-covered surface of simple cuboidal epithelium and simple columnar epithelium cells found in certain locations of the body. Microvilli are approximately 100 nanometers in diameter and their length varies from approximately 100 to 2,000 nanometers in...

. This leads to a reduction in the enterotoxinic and cytotoxic effects of C. difficile infection.

Antimicrobial effects

Escherichia coli
Escherichia coli
Escherichia coli is a Gram-negative, rod-shaped bacterium that is commonly found in the lower intestine of warm-blooded organisms . Most E. coli strains are harmless, but some serotypes can cause serious food poisoning in humans, and are occasionally responsible for product recalls...

and Salmonella typhimurium, two pathogenic bacteria often associated with acute infectious diarrhea, were shown to strongly adhere to mannose
Mannose
Mannose is a sugar monomer of the aldohexose series of carbohydrates. Mannose is a C-2 epimer of glucose. It is not part of human metabolism, but is a component of microbial cell walls, and is therefore a target of the immune system and also of antibiotics....

 on the surface of S. boulardii via lectin
Lectin
Lectins are sugar-binding proteins that are highly specific for their sugar moieties. They play a role in biological recognition phenomena involving cells and proteins. For example, some viruses use lectins to attach themselves to the cells of the host organism during infection...

 receptors (adhesin
Adhesin
Adhesins are cell-surface components or appendages of bacteria that facilitate bacterial adhesion or adherence to other cells or to inanimate surfaces. Adhesins are a type of virulence factor....

s). Once the invading microbe is bound to S. boulardii, it is prevented from attaching to the brush border
Brush border
A brush border is the name for the microvilli-covered surface of simple cuboidal epithelium and simple columnar epithelium cells found in certain locations of the body. Microvilli are approximately 100 nanometers in diameter and their length varies from approximately 100 to 2,000 nanometers in...

; it is then eliminated from the body during the next bowel movement.

Trophic effects on enterocytes

The hypersecretion of water and electrolytes (including chloride
Chloride
The chloride ion is formed when the element chlorine, a halogen, picks up one electron to form an anion Cl−. The salts of hydrochloric acid HCl contain chloride ions and can also be called chlorides. The chloride ion, and its salts such as sodium chloride, are very soluble in water...

 ions), caused by cholera
Cholera
Cholera is an infection of the small intestine that is caused by the bacterium Vibrio cholerae. The main symptoms are profuse watery diarrhea and vomiting. Transmission occurs primarily by drinking or eating water or food that has been contaminated by the diarrhea of an infected person or the feces...

 toxin during a Vibrio cholerae
Vibrio cholerae
Vibrio cholerae is a Gram-negative, comma-shaped bacterium. Some strains of V. cholerae cause the disease cholera. V. cholerae is facultatively anaerobic and has a flagella at one cell pole. V...

infection, can be reduced significantly with the introduction of S. boulardii. A 120 kDa protease
Protease
A protease is any enzyme that conducts proteolysis, that is, begins protein catabolism by hydrolysis of the peptide bonds that link amino acids together in the polypeptide chain forming the protein....

 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
Adenylate cyclase
Adenylate cyclase is part of the G protein signalling cascade, which transmits chemical signals from outside the cell across the membrane to the inside of the cell ....

, which led to the reduction in enterocytic cyclic adenosine monophosphate
Cyclic adenosine monophosphate
Cyclic adenosine monophosphate is a second messenger important in many biological processes...

 (cAMP) production and chloride secretion.

During an E. coli infection, myosin light chain (MLC) is phosphorylated leading to the degradation of the tight junctions between intestinal mucosa enterocyte
Enterocyte
Enterocytes, or intestinal absorptive cells, are simple columnar epithelial cells found in the small intestines and colon. A glycocalyx surface coat contains digestive enzymes. Microvilli on the apical surface increase surface area for the digestion and transport of molecules from the intestinal...

s. S. boulardii has been shown to prevent this phosphorylation
Phosphorylation
Phosphorylation is the addition of a phosphate group to a protein or other organic molecule. Phosphorylation activates or deactivates many protein enzymes....

, leading to a reduction in mucosal permeability
Vascular permeability
Vascular permeability, often in the form of capillary permeability, characterizes the capacity of a blood vessel wall to allow for the flow of small molecules or even whole cells in and out of the vessel. Blood vessel walls are lined by a single layer of endothelial cells...

 and thus a decrease in the translocation of the pathogenic bacteria.

Polyamine
Polyamine
A polyamine is an organic compound having two or more primary amino groups .This class of compounds includes several synthetic substances that are important feedstocks for the chemical industry, such as ethylene diamine , 1,3-diaminopropane , and hexamethylenediamine...

s (spermidine
Spermidine
Spermidine is a polyamine involved in cellular metabolism. Its known actions include:#Inhibition of neuronal nitric oxide synthase, nNOS#Assisting the in vitro process of transcribing RNA via stimulation of T4 polynucleotide kinase and T7 RNA polymerase activity; it binds to and precipitates DNA...

 and spermine
Spermine
Spermine is a polyamine involved in cellular metabolism found in all eukaryotic cells. Formed from spermidine, it is found in a wide variety of organisms and tissues and is an essential growth factor in some bacteria. It is found as a polycation at physiological pH...

) have been observed to be released from S. boulardii in the rat ileum
Ileum
The ileum is the final section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear and the terms posterior intestine or distal intestine may be used instead of ileum.The ileum follows the duodenum...

. Polyamine
Polyamine
A polyamine is an organic compound having two or more primary amino groups .This class of compounds includes several synthetic substances that are important feedstocks for the chemical industry, such as ethylene diamine , 1,3-diaminopropane , and hexamethylenediamine...

s 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.

Anti-inflammatory effects

Interleukin 8
Interleukin 8
Interleukin-8 is a chemokine produced by macrophages and other cell types such as epithelial cells. It is also synthesized by endothelial cells, which store IL-8 in their storage vesicles, the Weibel-Palade bodies...

 (IL-8) is a proinflammatory cytokine
Cytokine
Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...

 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
Inflammatory bowel disease
In medicine, inflammatory bowel disease is a group of inflammatory conditions of the colon and small intestine. The major types of IBD are Crohn's disease and ulcerative colitis.-Classification:...

. 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
Lipopolysaccharide
Lipopolysaccharides , also known as lipoglycans, are large molecules consisting of a lipid and a polysaccharide joined by a covalent bond; they are found in the outer membrane of Gram-negative bacteria, act as endotoxins and elicit strong immune responses in animals.-Functions:LPS is the major...

 (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
Interleukin 6
Interleukin-6 is a protein that in humans is encoded by the IL6 gene.IL-6 is an interleukin that acts as both a pro-inflammatory and anti-inflammatory cytokine. It is secreted by T cells and macrophages to stimulate immune response, e.g. during infection and after trauma, especially burns or other...

 were notably reduced, while the secretion of anti-inflammatory IL-10
Interleukin 10
Interleukin-10 , also known as human cytokine synthesis inhibitory factor , is an anti-inflammatory cytokine. In humans IL-10 is encoded by the IL10 gene....

 did increase. Finally Saccharomyces boulardii supernatant inhibited the proliferation of naïve T-cells in a mixed lymphocyte reaction (MLR) with mDC.

Increased levels of disaccharidases

The trophic effect on enterocytes has been shown to increase levels of disaccharidases such as lactase
Lactase
Lactase , a part of the β-galactosidase family of enzymes, is a glycoside hydrolase involved in the hydrolysis of the disaccharide lactose into constituent galactose and glucose monomers...

, sucrase
Sucrase
Sucrase is the name given to a number of enzymes that catalyze the hydrolysis of sucrose to fructose and glucose. The enzyme invertase, which occurs more commonly in plants, also hydrolyzes sucrose but by a different mechanism.-Physiology:...

, maltase
Maltase
Maltase is an enzyme that breaks down the disaccharide maltose. Maltase is an enzyme that catalyzes the hydrolysis of the disaccharide maltose to the simple sugar glucose. This enzyme is found in plants, bacteria, and yeast. Then there is what is called Acid maltase deficiency...

, 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. 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
Immunoglobulin A
Immunoglobulin A is an antibody that plays a critical role in mucosal immunity. More IgA is produced in mucosal linings than all other types of antibody combined; between three and five grams are secreted into the intestinal lumen each day....

 (IgA) in the small intestine of the rat. Secretory IgA provides protection against invading microbes in the gastrointestinal and respiratory tracts.

Human disease

Some cases of fungemia
Fungemia
-Pathogens:The most commonly known pathogen is Candida albicans, causing roughly 70% of fungemias, followed by Candida glabrata with 10%, Aspergillus with 1% and Saccharomyces as the fourth most common. However, the frequency of infection by C. glabrata, Saccharomyces boulardii, Candida tropicalis,...

 have been reported, especially those with certain digestive disorders, or patients with a central venous catheter
Central venous catheter
In medicine, a central venous catheter is a catheter placed into a large vein in the neck , chest or groin...

. 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
Probiotic
Probiotics are live microorganisms thought to be beneficial to the host organism. According to the currently adopted definition by FAO/WHO, probiotics are: "Live microorganisms which when administered in adequate amounts confer a health benefit on the host"...

 supplements for the treatment of Clostridium difficile
Clostridium difficile
Clostridium difficile , also known as "CDF/cdf", or "C...

colitis, can possibly cause fungemia in critically ill patients.
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