Saccharomyces boulardii in gastroenterological practice

In recent years, there has been a growing number of publications devoted to various aspects of the use of probiotics not only in gastroenterology. Interest in probiotics is due to the need to use drugs with physiological effects that do not cause harm to the human body. The use of ever new antibiotics, immunosuppressants, other chemotherapeutic drugs, and hormonally active agents inevitably leads to disruption of the human intestinal microbiocenosis and weakening of immune defense mechanisms. In these conditions, the use of drugs that are alternative to antibiotics or reduce the incidence of side effects of aggressive chemotherapy is very important.

Among probiotics, the drug Enterol®, which is a non-pathogenic yeast fungus Saccharomyces boulardii obtained from tropical plants, is increasingly being used. S. boulardii lives and reproduces at an unusually high temperature of 37 °C, which corresponds to the temperature regime in the intestinal cavity (McFarl, 1995), and has a very high viability [1].

S. boulardii belongs to the ascomycetes that have genetically determined resistance to almost all groups of antibiotics, sulfonamides and other antimicrobial agents [2–5]. This property fundamentally distinguishes Enterol® from other microbial probiotics based on bacteria of obligate intestinal microflora (containing bifidobacteria, lactobacilli, fecal enterococcus) and allows its use simultaneously with a course of antibacterial therapy. S. boulardii does not suppress the growth of obligate microorganisms in the intestinal cavity.

The relationship of S. boulardii with antifungal drugs varies. Thus, fungicides that are not absorbed from the intestine (nystatin) completely suppress the growth of the fungus, and when taking absorbable fungicides (fluconazole), the viability of the yeast is completely preserved [6].

S. boulardii is resistant to hydrochloric acid and, when taken daily, is found in all parts of the gastrointestinal tract (GIT) [4, 7–9]. This yeast is a transient flora for humans, therefore, 2–5 days after the end of taking the drug, it is completely eliminated from the body without side effects [7, 10]. Enterol® is a locally acting intestinal antiseptic and is not absorbed from the gastrointestinal tract. It is mainly used for diarrhea of various origins with a predominantly secretory mechanism of development - bacterial and viral diarrhea.

The mechanism of action of Enterol® is determined by several aspects [11, 12]:

direct antimicrobial effect;
direct and indirect antitoxic effect (binding of microbial toxins in the intestine);
antisecretory effect (reduces intestinal secretion of water and electrolytes during secretory diarrhea);
direct and indirect antiviral effect;
trophic effect (stimulates the enzymatic activity of intestinal disaccharidases and other digestive enzymes);
nonspecific immunomodulatory effect.

Experimental data

The direct antimicrobial effect of Enterol® has been established in vitro and in vivo against a number of pathogens of intestinal infections, opportunistic microorganisms and protozoa [11, 13–16]: Salmonella typhimurium, Yersinia enterocolitica, Escherichia coli, Clostridium difficile, Shigella dysenteriae, Entamoeba histolitica , Giardia lamblia, Candida albicans, C. krusei, C. pseudotropicalis, Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, etc.

Such a wide range of antimicrobial effects determines the use of Enterol® as an antidiarrheal and antiseptic agent for acute intestinal infections (as an alternative to antibiotics when their use is impossible); antibiotic-associated diarrhea and pseudomembranous colitis caused by C. difficile; parasitic diarrhea and intestinal dysbiosis, including microbial contamination of the small intestine with conditional pathogens.

The ability of Enterol® to suppress the growth of fungi of the genus Candida can be successfully used in case of fungal contamination of the intestine. In an experiment on mice in a state of artificial immunosuppression with antibiotics and prednisolone, it was shown that S. boulardii prevents the generalization of C. albicans fungi into the blood, lymph nodes and spleen [13].

The effectiveness of S. boulardii in dysentery with positive changes at the histological level has been demonstrated in mice. When using S. boulardii, the survival rate of mice was 75% versus 32% in the control group [13]. The same effect was demonstrated for S. typhimurium (50% and 20%). Interestingly, all the positive dynamics and survival of experimental animals when taking S. boulardii are not due to a decrease in the number of pathogenic microorganisms in the intestines of animals. The proposed mechanism of action is adhesion and lectin-mediated binding of infectious agents to specific sites on the outer membrane of yeast cells. This mechanism has been proven for S. typhimurium, S. enteritidis and some serotypes of E. coli [11, 15].

The antitoxic effect of Enterol®, its ability to bind bacterial cyto- and enterotoxins enhance the antimicrobial effect, and as an independent mechanism it can be used for foodborne toxic infections, for example, staphylococcal infections. Inhibition of the activity of bacterial toxins, in particular cholera and heat-labile toxin Escherichia coli, leads to a decrease in the secretion of water and electrolytes and a weakening of the diarrheal syndrome caused by these toxins [17–19]. Diarrhea associated with these infections is a classic example of cAMP-dependent secretory diarrhea. The mechanism of the antitoxic action of S. boulardii is due to the production of certain proteins.

One of these proteins, with a molecular weight of 120 kDa, does not have proteolytic activity, but inhibits the synthesis of cyclic adenosine monophosphate (cAMP) and thus reduces the symptoms of diarrhea. Thanks to this mechanism, the survival rate of animals infected with these microorganisms and treated with S. boulardii increases [20]. The other protein is a small protease (54 kDa) capable of lysing C. difficile toxin A, which stimulates intestinal secretions and increases the permeability of the intestinal mucosa. The use of S. boulardii in rats infected with clostridium helps reduce the severity of damage to the mucous membrane [5, 19, 21].

The trophic immunomodulatory effect of Enterol® is due to its ability to synthesize polyamines (spermine, spermidine) [12]. Polyamines stimulate the activity of digestive enzymes in the small intestine: they increase the production of saccharidases (lactase, maltase, sucrase) and amnopeptidases, which leads to weight gain in experimental animals [11]. The trophic effect of Enterol® is extremely important when bacteria and viruses damage the intestinal mucosa and, as a result, reduce the activity of digestive enzymes. In addition, polyamines stimulate the synthesis of IgA and components of other immunoglobulins in the intestinal mucosa [12].

The indirect antiviral activity of Enterol® is associated with its ability to increase local immune defense of the intestine, enhance the synthesis of IgA, produce polyamines and stimulate trophic effects.

Clinical studies of the effectiveness of S. boulardii, conducted in the period 1976–2000, showed that the drug is highly effective against diarrhea of various origins, mainly of infectious origin.

Antibiotic-associated diarrhea

Double-blind, randomized studies conducted in a variety of antibiotic-requiring infections have demonstrated that the use of S. boulardii reduces the incidence of antibiotic-associated diarrhea by two to four times. Thus, in one study involving 388 patients, the incidence of diarrhea in the group of patients taking S. boulardii along with antibiotics was 4.5% versus 17.5% in the placebo group. In two other studies (180 and 193 patients), these values were 9.5% versus 22% and 7.2% versus 14.6%, respectively [22–24]. In these studies, the causative agent of diarrhea was not identified.

Acute diarrhea

The effectiveness of the drug was studied in controlled studies for acute diarrhea in adults and children. In 92 adult patients with acute diarrhea, administration of S. boulardii after 48 hours resulted in a significant reduction in the number of bowel movements and changes in stool consistency compared with the placebo group [27]. Similar results were demonstrated in 130 children aged three months to three years with acute diarrhea [28] and in two earlier randomized trials of similar design [29, 30].

Traveler's diarrhea

The double-blind, placebo-controlled study involved 1,231 international travelers [31]. The results showed that in the placebo group the incidence of diarrhea averaged about 43%, and in the group receiving S. boulardii for the prevention of diarrhea it averaged 31%, which was significantly lower. Interestingly, the study results varied by region. The highest effectiveness of the drug (i.e., the proportion of study participants without developing diarrhea) was noted in Africa (up to 59%) and on tropical islands (about 40%), in other regions this figure was lower. These differences can probably be explained by different pathogens causing traveler's diarrhea in different regions and their different sensitivities to the drug. The study used two doses of the drug: 250 and 500 mg per day. There were no differences in the incidence of diarrhea depending on the dose.

Conclusion

Although the mechanism of action of Enterol® still remains unclear, the results of its long-term clinical use indicate its high effectiveness and safety. Thanks to its complex antidiarrheal, antimicrobial, antiviral and antitoxic effects, Enterol® can be an additional or primary treatment for secretory infectious diarrhea in adults and children. The trophic, immunomodulatory and digestion-stimulating effect of the drug helps overcome the consequences of severe infections.

For questions regarding literature, please contact the editor.

E. L. Belousova , Doctor of Medical Sciences, Professor

MONIKA them. M. F. Vladimirsky, Moscow

Effect of the yeast Saccharomyces cerevisiae on inflammatory bowel disease

18.03.2017 10:06
INFLUENCE OF BAKER'S YEAST ON INFLAMMATORY BOWEL DISEASES

Common baker's yeast Saccharomyces cerevisiae may worsen IBD symptoms in Crohn's disease

Over the past decade, gastroenterology as a science has experienced, shall we say, a “rebirth,” as more and more research focuses on understanding the role of the microbiome in human health.

Scientists at the University of Utah Health Sciences used mice in their study to show the role of yeast in worsening the symptoms of inflammatory bowel disease.

Inflammatory bowel disease (IBD) is an autoimmune disease characterized by chronic inflammation of the gastrointestinal tract, resulting in severe diarrhea, abdominal pain, fatigue and weight loss. For decades, doctors have used yeast antibodies, especially antibodies to the cell wall of the yeast Saccharomyces cerevisiae, to differentiate between disease (CD) and ulcerative colitis (UC) (ie, to differentiate between the two types of IBD). However, it was not clear exactly what role yeast plays in the life of an IBD patient.

Note ed.: Differential diagnosis is a diagnostic method in medicine that excludes diseases that are not suitable for any facts or symptoms that are possible in a patient, which ultimately should reduce the diagnosis to the only probable disease. In popular culture, differential diagnosis is used in the television series House, by House and his team. Using the method of elimination, they quickly make the correct diagnosis, having first written the symptoms and possible diseases on the board.

“Until recently, there was a huge gap in our understanding of the role of yeast in IBD and overall human health,” said June Round, assistant professor of pathology and PhD at the University of Utah Health Sciences.

It is now easy to find information about the many types of yeast in the human gastrointestinal system, but the research team chose only two species that were common to the intestinal microbiota of healthy people and patients with UC or CD.

Saccharomyces cerevisiae, also known as baker's yeast, is found in the environment and in baked goods. Rhodotorula aurantiaca is usually found in milk and fruit juice.

In this study, the researchers gave each type of yeast to mice that had previously been artificially (chemically) induced to exhibit IBD-like symptoms. Symptoms only increased in mice fed Saccharomyces cerevisiae.

“Mice fed Saccharomyces cerevisiae experienced significant weight loss, diarrhea, and bloody stools, just like humans with inflammatory bowel disease,” says Tyson Chiaro, a graduate student in the lab.

In order to decipher the findings, scientists examined the feces of mice fed Saccharomyces cerevisiae. As a result, these mice had higher concentrations of nitrogen-rich compounds called purines in their feces than mice fed Rhodotorula aurantiaca.

Unlike other yeast species, Saccharomyces cerevisiae cannot break down purines, which accumulate in the intestinal tract and are converted into another compound ( uric acid ). Uric acid exacerbates inflammation, which can worsen IBD symptoms.

In addition to this study, the scientists examined serum samples from healthy adults.

“We found that every human blood sample with high antibodies to Saccharomyces cerevisiae also had high levels of uric acid,” reports Tyson Chiaro.

Although only a subset of IBD patients had high levels of the yeast Saccharomyces cerevisiae, the results of this study support the idea that the yeast makes the disease worse and that a cure may be on the way.

To test this theory, scientists gave experimental mice Allopurinol (a drug used to prevent the formation of uric acid in patients with gout). Allopurinol significantly reduced intestinal inflammation in these mice.

“Our work suggests that if we can block the mechanism that leads to uric acid production in IBD patients with high concentrations of antibodies to Saccharomyces cerevisiae, there may be a new treatment option for their disease,” explains Dr. Round.

June Round wants to continue working on this issue by studying the interaction of bacteria and yeast in the gut, as well as conduct clinical trials of Allopurinol, testing its effect on the symptoms of human inflammatory bowel disease.

“Yeast and bacteria can influence each other's biology in our gut, but we don't know how this interaction affects human disease. Our team will continue to study the role of intestinal microorganisms in our well-being,” June Round concluded.

Source: ScienceDaily

Journal article:

Tyson R. Chiaro, Ray Soto, W. Zac Stephens, Jason L. Kubinak, Charisse Petersen, Lasha Gogokhia, Rickesha Bell, Julio C. Delgado, James Cox, Warren Voth, Jessica Brown, David J. Stillman, Ryan M. O 'Connell, Anne E. Tebo, June L. Round. A member of the gut mycobiota modulates host purine metabolism exacerbating colitis in mice. Science Translational Medicine, 2017

See also: Disruption of the early development of healthy intestinal microflora by antibiotics leads to inflammatory diseases