SACCHAROMYCES BOULARDII

BACKGROUND

Ingredient Type: Fungi

Also Known As: S. boulardii, Brewer’s Yeast, Hansen CBS 5926, Levure de Boulanderie, Probiotic, Probiotique, Saccharomyces, Saccharomyces Cerevisiae

Saccharomyces boulardii, or S. boulardii, is a form of yeast that was first in the 1920’s by the French scientist, Henri Boulard. The yeast was initially isolated from both tropical fruit peels of lychee and mangosteen. Henri noticed a Southeast Asian native chewing on the skin of the plant to ward off the symptoms associated with cholera. It was recognized that S. boulardii was responsible as a cholera-preventing agent (13).

Although early studies have indicated that S. boulardii, has its own distinct metabolic and genetic properties (12), it is still considered genetically a grouping of the S. cerevisiae strain as it shares about 99% of its genomic relatedness. S. boulardii is known to be found mainly in the gastrointestinal tract in healthy individuals; in this case, it is not normally considered a systemic or pathogenic yeast.

TRADITIONAL USES

Since the identification of S. boulardii in France, Henri continued to study and test this yeast for the next 30 years as a stomach remedy. Around the mid-1950s, Henri sold the discovery of S. boulardii to a French pharmacist who later commercialized it in France. Since this time, S. boulardii has been used as probiotic for various ailments.

Today, S. boulardii has both medicinal, as well as nutraceutical uses. Some of the more common uses include preventing or treating diarrhea due to certain infections or gastrointestinal flora imbalances, supporting digestion problems, irritable bowel syndrome, inflammatory bowel syndrome, colitis due to Clostridium difficile, as well as lactose intolerance, urinary tract infections and vaginal yeast infections.

WHAT DOES SCIENCE TELL US?

1. boulardii and Diarrhea

1. boulardii is considered one of the more common live strains used to resolve acute forms or diarrhea. This study was conducted to determine whether an orally administered pharmaceutical containing S. boulardii has the ability to reduce the duration of acute diarrhea in infants. The study consisted of 186 infants between the ages of 6 – 48 months old, experiencing acute onset with hospitalization occurring within 72 hours of symptom onset. Infants were randomly assigned to receive 2 doses of 200mg of the noted pharmaceutical for a duration of 5 days. The pharmaceutical product contained either 4 x 10 viable cells of S. boulardii or a placebo. Among those who completed the trial, totaling 176 infants, those treated with the S. boulardii pharmaceutical (90 infants) noted a significant reduction in diarrhea when compared to the placebo group (86 infants) (4).

A similar multicentric, double-blind, randomized, controlled study was conducted to assess the effectiveness of a specific formula that was fortified with S. boulardii in its ability to manage or resolve infants with acute onset diarrhea. The study consisted of 70 infants who were on average 5 months old, presenting with acute diarrhea (6 + stools per day). 36 of the infants were randomly assigned to the standard, control formula while 34 of the infants were randomly assigned to the formula fortified with S. boulardii. For comparative purposes, age, inclusion, weight, and average number of stools were kept consistent. 15 infants in each group were diagnosed with rotavirus concurrently to this study. As noted by the researchers, there was a significant improvement in duration of diarrhea when observed in the treatment vs. the control group. It was additionally noted that the results were not dependent on the presence or absence of rotavirus. Upon review of the results, it was concluded that specially designed formulas fortified with S. boulardii, can aid in reducing the duration of acute diarrhea in moderately dehydrated infants (11).

Diarrhea, specifically antibiotic-resistant (AAD) and Clostridium difficile-associated diarrhea (CDAD), is a common complication due to the overuse of antibiotics. Although various studies have assessed the usefulness of probiotics in resolving the associated symptoms of such conditions, the efficacy of probiotics to prevent diarrhea related to AAD and CDAD is still unclear. The purpose behind this multicenter, randomized, placebo-controlled trial was to further study the activity of an S. boulardii fortified product, Perenterol forte, in patients who experienced diarrhea in response to AAD and/or CDAD. Of 2,444 patients, 477 individuals participated. 246 patients and 231 patients were randomly assigned to either the Perenterol forte or control group respectively. Unfortunately, due to futility, the study was stopped. Researchers did not find any substantial evidence indicating the effectiveness of S. boulardii in preventing the side effects associated with AAD or CDAD (5).

A commonly known and frequent side effect of antibiotic therapy is antibiotic-associated diarrhea (AAD). Symptoms can be observed as mild to life threatening (i.e., pseudomembranous colitis). Unfortunately, like many virus encounters, therapy is symptomatic for such AADs. Due to the promising effects of other antidiarrheal alternatives, such as S. boulardii, researchers have sought to analyze its activity and effectiveness further to identify whether it can be used as a safe and effective alternative for merely symptomatic-focused antidiarrheal drugs. A review was conducted to assess the current studies involving S. boulardii in its ability to prevent AAD. The results revealed, in 14 of the 17 studies, that S. boulardii had a significant, protective effect on between 43.7 – 873% of the 4,627 patients observed in this review. According to the results obtained in this review, the researchers concluded that there is very good evidence for S. boulardii to be utilized as an alternative in the prevention of AAD, especially in hospitalized adults (14).

1. boulardii and Irritable Bowel Syndrome

This controlled, double-blind, randomized study was conducted to further research the ability of S. boulardii to treat IBS associated symptoms, specifically diarrhea. A total of 70 patients participated in this study who were clinically diagnosed with IBS, 35 patients in each of the control and studied, treatment group. The test group received 250mg of S. boulardii orally for a one-month duration. Patients in both the control group and the treatment group were evaluated before, at the conclusion of and 30 days following the conclusion of treatment. The evaluation and scoring consisted of the presence or absence of symptoms, as well as how the respective symptoms affected the individuals both personally and professionally. Upon reviewing the scores and symptoms at the conclusion of and 30 days following completion of this study, no significant differences were observed between the treatment and control group in any of the parameters evaluated.  According to the researchers, no improvement was observed in the IBS patients during the duration of or following the study (9).

Another similar study was conducted on patients who presented with diarrhea-predominant IBS (IBS-D) to determine whether the combined or alone therapies of mesalazine and lyophilized S. boulardii would support amelioration of IBS-D associated symptoms. These specific therapies were selected due to their effectiveness in supporting gastrointestinal disorders. Mesalazine has intestinal anti-inflammatory properties, while S. boulardii is recognized to treat various forms of diarrhea, specifically infectious diarrhea. 53 patients with IBS-D were selected to participate in this study. In order to properly exclude organic diseases that would alter the outcome of this study, patients were required to undergo a colonoscopy, a stool culture, tolerance and sensitivity tests, as well as an ova and parasite exam. The participants were divided in to 3 groups: a mesalazine group (MG) – 20 patients, an S. boulardii group – 12 patients and a mesalazine and S. boulardii group – 21 patients (MSbG). The treatment duration for this study occurred over 30 days where each patient received one of the therapies 3 times daily. Upon assessing the measurables for this study, symptom evaluation, 4-point likert scale, Bristol scale and a Kruskal-Wallis test, the results indicated that use of either mesalazine or S. boulardii alone, or combined produced significant improvements in IBS-D symptoms. The researchers concluded that both mesalazine and S. boulardii may be useful alternatives in the treatment of IBS-D, although further research is necessary to reinforce the results (1).

1. boulardii and Crohn’s Disease

The health of the intestinal microflora plays a vital role in the maintenance of inflammation, especially regarding Chron’s Disease (CD). Such biotherapeutics are continuously being studied and tested to identify alternative therapies for inflammatory bowel diseases. For example, two pilot studies were conducted utilizing S. boulardii (Perenterol®) at dosages of 750 – 1000mg for up to 6 months. Aside from higher risk, hospitalized patients with catheters, use of Perenterol® has been considered safe and well tolerated (8).

In this study, the beneficial effects of S. boulardii on the gastrointestinal tract was assessed, more specifically with regards to the maintenance of Chron’s disease (CD). A total of 32 patients with CD in clinical remission participated in this clinical trial. Participants were randomly treated for a duration of six months with either 1g t.i.d. of mesalamine, 1g b.i.d. of mesalamine and 1 g of S. boulardii q.d. According to the results of the study, clinical relapses were observed in 37.5% of the treatment group receiving the mesalamine alone while only 6.25% of those receiving the mesalamine and S. boulardii were noted with a clinical relapse. It is suggested that S. boulardii may be a useful alternative in the maintenance and treatment of CD, although much more research is necessary to reinforce the clinical data obtained in this study (6).

With much research focused on probiotics and their beneficial activity, many physicians and researchers are studying about how such alternatives can possibly be utilized on the clinical side to treat various ailments. With Chron’s disease (CD) being one of the more common inflammatory gastrointestinal disorders, there is suggestion that S. boulardii could potentially be used to treat patients with CD. A prospective study was conducted on 165 patients who had already achieved remission following treatment with steroids. These participants were randomly assigned either into the treatment group of who were given S. boulardii at 1g/ day or the placebo group for a duration of 52 weeks. With regard to this study, the parameters assessed included time to relapse, if relapse occurred, CD activity index scores, as well as degree of inflammation present. Of the 165 participants, 80 patients had a CD relapse (38 from the S. boulardii group; 42 from the placebo group). Additionally, there was no significant difference with respect to the CD activity index scores. Although consumption of S. boulardii is considered safe and observed as well-tolerated by majority of the studies, it does not appear to have much of a beneficial effect with regard to patients with CD (3).

1. boulardii and Intestinal Flora

Similar to many gastrointestinal disorders, gut microbiome is often a key factor in determining the health of the gastrointestinal tract, along with its associated, surrounding organs. One example is the liver. This study investigates the use of S. boulardii as an alternative, protective therapy for hepatosis. Subjects received D-Galactosamine-induced liver injury in preparation for the study. Upon receipt of the S. boulardii therapy, both a hepatic function test as well as histopathological analysis indicated S. boulardii’s ability to attenuate the hepatic damage.

Additionally, dramatic changes in the gut microbiome were resultant of the S. boulardii administration. It is hypothesized that the rebalance in intestinal flora resulted in the hepatoprotective effects of S. boulardii, particularly an increase in abundance of Bacteroidetes and a decrease in abundance of Firmicutes and Proteobacteria. From the observations, researchers concluded that S. boulardii could support healthier microbiota environments, thereby potentially resulting in the alleviation of acute liver failure due to its observed protective and therapeutic activity (21).

A common tie to intestinal barrier defects or “leaky gut” is an imbalance of gastrointestinal flora. When there is an imbalance of beneficial flora, inflammation, and damage to the lining of the gastrointestinal tract is a common response. This often can lead to what is known as intestinal permeability which allows for the passage of luminal content into the bloodstream as well as the intestinal tissues. Intestinal barriers with such compromised integrity are often the main factor inherent in the pathogenesis of many inflammatory bowel diseases. The non-pathogenic yeast, S. boulardii, has been studied and demonstrated to yield favorable results as it relates to the prevention and treatment of antibiotic-associated functional and infectious diarrhea. It is said that the activity of S. boulardii promotes the alteration of intestinal microbiota and mending of epithelial barriers. Due to the ability of S. boulardii to support the preservation and restoration of the intestinal barrier, it continues to be selected for study in diseases associated with alterations in intestinal barrier integrity and function (17).

An imbalance of flora in the gastrointestinal tract has commonly been linked with exacerbating that state of inflammation in patients with various acute, as well as chronic conditions. With respect to patients with HIV, such an imbalance has been linked to an increase in microbial translocation, resulting in an imbalance that has been found to lead to further chronic inflammation. Such microbial translocation has further been found to contribute to the pathogenesis of a non-responsive immune system within patients with HIV. This double-blind, randomized, placebo-controlled study assessed the comparison between treatment with S. boulardii and a placebo on the degree of bacterial translocation and systemic inflammation, thereby determining if the effectiveness of S. boulardii was due to a modified gastrointestinal microbiome. Of the 44 patients, over a period of 12 weeks, the researchers observed a significant difference between the treatment and placebo group as it related to bacterial translocation levels and systemic inflammation. It was concluded that administration of S. boulardii could be an excellent alternative in supporting patients with HIV. The process of measuring the gastrointestinal microbiome could also prove to be an effective way in assessing reduced inflammatory responses (19).

SAFETY

The safety of S. boulardii is often associated with little to no side effects when considering individuals with normal to optimal immune systems. When it comes to individuals who are considered immunocompromised, such yeasts and probiotics have been associated with complications such as fungemia and exacerbation of localized infections (15, 20). It has been identified that about 100 cases of S. boulardii– associated fungemia have been recorded, although the vehicle tor fungemia in each of these cases has not been pinpointed (18).

Regarding the severity, fungemia is only second to the administration of probiotics to patients with gastrointestinal disease who have had or have an indwelling catheter (7). Overall, the use and consumption of S. boulardii is considered safe with mild to limited side effects. It is however recommended that individuals with a compromised immune system should practice caution when taking any form of pro or prebiotic. It is in one’s best interest to consult with your medical professional about the potential risks and complications associated with your condition.

SIDE EFFECTS

The reported side effects of S. boulardii is quite limited to gastrointestinal discomfort, constipation, and gas. Outside of these side effects, S. boulardii is considered safe for consumption for up to 15 months at a time. If any side effects arise and/or persist for a couple weeks, it is recommended to consult with your professional healthcare provider.

Children – With regard to children, S. boulardii is probably safe if taken in the appropriate dosages by mouth. If, however there are any changes in their bowel or eating habits, it is best to consult with your medical professional to ensure the continued health and safety of your child.

Pregnant or Women Breastfeeding – Due to the limited, reliable research regarding S. boulardii consumption and pregnancy or breastfeeding, it is recommended to consult with your medical professional prior to supplementation to ensure the health and safety of yourself as well as your unborn child.

Yeast Allergy – If you have been diagnosed or recognize you are with a yeast allergy or sensitivity, it is recommended to avoid the consumption and/or use of any products containing S. boulardii, as this probiotic is in a yeast form not bacterial.

INTERACTIONS

The only real concern for interactions when it comes to S. boulardii, is for those individuals’ taking medications for fungal infections. Due to the nature of S. boulardii being a yeast-form of fungus, supplementing with this while on medications to reduce the presence of fungus in the body will also reduce the effects of S. boulardii.

While this is not an exhaustive list, these are some of the antifungal medications that are commonly prescribed for remediation of fungus (yeast, mold): Nystatin, Amphotericin B, Clotrimazole, Ketoconazole, Miconazole, Fluconazole, Itraconazole, Posaconazole, Voriconazole, Anidulafungin, Caspofungin, Micafungin

REFERENCES

1. Bafutto, Mauro et al. “Treatment of diarrhea-predominant irritable bowel syndrome with mesalazine and/or Saccharomyces boulardii.” Arquivos de gastroenterologia 50,4 (2013): 304-9. doi:10.1590/S0004-28032013000400012
2. 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 andchildren”. European Review for Medical and Pharmacological Sciences. 15 (7): 809–22
3. Bourreille, Arnaud et al. “Saccharomyces boulardii does not prevent relapse of Crohn’s disease.” Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 11,8 (2013): 982-7. doi: 10.1016/j.cgh.2013.02.021
4. Corrêa, Naflesia B O et al. “Treatment of acute diarrhea with Saccharomyces boulardii in infants.” Journal of pediatric gastroenterology and nutrition 53,5 (2011): 497-501. doi: 10.1097/MPG.0b013e31822b7ab0
5. Ehrhardt, Stephan et al. “Saccharomyces boulardii to Prevent Antibiotic-Associated Diarrhea: A Randomized, Double-Masked, Placebo-Controlled Trial.” Open forum infectious diseases 3,1 ofw011. 29 Jan. 2016, doi:10.1093/ofid/ofw011
6. Guslandi, M et al. “Saccharomyces boulardii in maintenance treatment of Crohn’s disease.” Digestive diseases and sciences 45,7 (2000): 1462-4. doi:10.1023/a:1005588911207
7. Hennequin C., Kauffmann-Lacroix C., Jobert A., Viard J.P., Ricour C., Jacquemin J.L., et al. (2000) Possible role of catheters in Saccharomyces boulardiifungemia. Eur J Clin Microbiol Infect Dis 19: 16–20
8. S Joossens, PhD, P Suenaert, MD, PhD, M Noman, MD, S Vermeire, MD, PhD, P Rutgeerts, MD, PhD, Saccharomyces Boulardiiin Crohn’s Disease: Effect on Anti-Saccharomyces Cerevisiae Antibodies and Intestinal Permeability, Inflammatory Bowel Diseases, Volume 11, Issue 9, 1 September 2005, Pages 863–864, https://doi.org/10.1097/01.MIB.0000183543.72225.08
9. Kabir, M A et al. “Role of Saccharomyces boulardii in diarrhea predominant irritable bowel syndrome.” Mymensingh medical journal: MMJ 20,3 (2011): 397-401.
10. Kelesidis T, Pothoulakis C (March 2012). “Efficacy and safety of the probiotic Saccharomyces boulardii for the prevention and therapy of gastrointestinal disorders”. Therapeutic Advantages in Gastroenterology. 5 (2): 11-25. doi:10.1177/1756283X11428502
11. Le Luyer, B et al. “Etude multicentrique, contrôlée en double insu d’une formule adaptée enrichie en Saccharomyces boulardii dans le traitement des diarrhées aiguës du nourrisson” [A multicentric study of a lactose free formula supplemented with Saccharomyces boulardii in children with acute diarrhea]. Archives de pediatrie : organe officiel de la Societe francaise de pediatrie 17,5 (2010): 459-65. doi: 10.1016/j.arcped.2010.02.004
12. Malgoire JY, Bertout S, Renaud F, Bastide JM, Mallie 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.43.4.1133-1137.2005.
13. McFarland, Lynne V. “Systematic review and meta-analysis of Saccharomyces boulardii in adult patients.” World journal of gastroenterology 16,18 (2010): 2202-22. doi:10.3748/wjg. v16.i18.2202
14. Micklefield, G. “Saccharomyces boulardii bei Antibiotika-assoziierter Diarrhöe” [Saccharomyces boulardii in the treatment and prevention of antibiotic-associated diarrhea]. MMW Fortschritte der Medizin 156 Suppl 1 (2014): 18-22.
15. 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:1177/039463201402700120
16. Sulik-Tyszka B, Snarski E, Niedzwiedzka 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
17. Terciolo, Chloe et al. “Beneficial effects of Saccharomyces boulardiiCNCM I-745 on clinical disorders associated with intestinal barrier disruption.” Clinical and experimental gastroenterology 12 67-82. 11 Feb. 2019, doi:10.2147/CEG.S181590
18. Vandenplas Y., Brunser O., Szajewska H. (2009) Saccharomyces boulardiiin childhood. Eur J Pediatr 168: 253–265
19. Villar-García, Judit et al. “Impact of probiotic Saccharomyces boulardii on the gut microbiome composition in HIV-treated patients: A double-blind, randomized, placebo-controlled trial.” PloS one 12,4 e0173802. 7 Apr. 2017, doi: 10.1371/journal.pone.0173802
20. Whelan K., Myers C.E. (2010) Safety of probiotics in patients receiving nutritional support: a systematic review of case reports, randomized controlled trials, and nonrandomized trials. Am J Clin Nutr91: 687–703
21. Yu, L., Zhao, Xk., Cheng, Ml. et al.Saccharomyces boulardii Administration Changes Gut Microbiota and Attenuates D-Galactosamine-Induced Liver Injury. Sci Rep 7, 1359 (2017). https://doi.org/10.1038/s41598-017-01271-9