Last update and review: June 30, 2020.
A short summary:
Another study shows that Saccharomyces boulardii do not resist to bile acids. The recommandation to take Saccharomyces boulardii one hour before a meal is, therefore, questionable.
Trehalose, a naturally occurring disaccharide comprised of two molecules of glucose, has interesting properties, but when added to food, may also contribute to Clostridium difficile overgrouth.
Survival of five Saccharomyces cerevisiae strains and of Saccharomyces boulardii after exposure to stresses tipical for gastrointestinal tract.
Martins et al., 2008 (1) studied five Saccharomyces cerevisiae strains isolated from Brazilian Atlantic rain forest as potential probiotics. The researchers measured trehalose contents and survival of the studied strains after exposure to a combination of physiological stresses generally found in the gastrointestinal tract of humans. The results in the five yearst were compared to the behavior of Saccharomyces boulardii, a well-known probiotic.
Martins et al., 2008 (1), used trehalose synthesis as a marker of stress in the different strains of potential probiotic strains and in Saccharomyces boulardii.
Synthesis of trehalose, a disaccharide comprised of two molecules of glucose, is one of the best-characterized responses to stress in microorganisms.
Martins et al., 2008 (1):
All microorganisms have the capacity of detect changes in environments and to cope with the deleterious effects of this alteration with rapid molecular responses to repair damage and protect themselves against further exposure to stress. One of the best-characterized responses involves the synthesis of trehalose. Intracellular accumulation of trehalose has been associated with increased thermotolerance of bacterial, yeast, and fungal cells (21). Besides heat, other stress conditions such as CuSO4, H2O2or ethanol concentrations and dehydration can also induce trehalose synthesis.
Saccharomyces boulardii survived well at 37 degrees Celsius and in the presence of gastric juice and a pH of 2.0.
89% of Saccharomyces boulardii survived after exposure to 37 degrees Celsius and in the presence of gastric juice and a pH of 2.0.
After one hour exposure to bile acids at 2mg/mL and 37 degrees Celsius, all Saccharomyces boulardii cells died.
Martins et al., 2008 (1):
Cultures harvested in exponential phase were transferred to YPG medium supplemented with a mixture of …bile salts, containing approximately 50% sodium cholate and 50% sodium deoxycholate and incubated during 60 min at 30ºC or 37ºC.
Exposure to bile salts constituted a highly aggressive stress for S. boulardii, since all the cells died after 1 h of this treatment.
Only 21% of Saccharomyces boulardii cells survived after exposure to pancreatic juice at pH of 8 and a temperature of 37 degrees Celsius.
Good news: some colonization by Saccharomyces boulardii did occur in the gut of gnotobiotic mice.
There is a piece of good news, however, since Martins et al., 2008 (1), found that some colonization of gut did occur in gnotobiotic mice.
Definition of gnotobiotic.
Encyclopedia Britannica:
Gnotobiotic organisms are of two major types: germfree, that is, free of all known contaminants; and gnotophoric, bearing a single known contaminant, usually administered as part of an experiment. The term “germfree,” however, is often used loosely to indicate all organisms cultivated under laboratory conditions in the absence of any other detectable species or in the presence of species known by the investigator to be present.
Yeast counts during ten days in the feces of gnotobiotic mice after a single inocculation.
What is trehalose?
Trehalose can prevent damage to mammalian eyes caused by desiccation and oxidative insult.
Luyckx et al., 2011 (2):
Trehalose is a naturally occurring disaccharide comprised of two molecules of glucose. The sugar is widespread in many species of plants and animals, where its function appears to be to protect cells against desiccation, but is not found in mammals. Trehalose has the ability to protect cellular membranes and labile proteins against damage and denaturation as a result of desiccation and oxidative stress. Trehalose appears to be the most effective sugar for protection against desiccation. Trehalose is under investigation for a number of medical applications, including the treatment of Huntington’s chorea and Alzheimer’s disease. Recent studies have shown that trehalose can also prevent damage to mammalian eyes caused by desiccation and oxidative insult. These unique properties of trehalose have thus prompted its investigation as a component in treatment for dry eye syndrome.
Trehalose was introduced to the food chain en masse during the early 2000s.
Collins et al., 2019 (3):
A disaccharide of glucose, trehalose was introduced to the food chain en masse during the early 2000s following a precipitous drop in manufacturing costs and “generally regarded as safe” (GRAS) status in the USA and Europe.
In humans, trehalose ingestion results in a significantly lower blood glucose peak when compared to ingestion of glucose.
“It is likely that not all of the trehalose is hydrolyzed to glucose and absorbed but rather an undetermined amount remains in the lumen where it is available for microbial fermentation.”
Collins et al., 2019 (3):
A number of studies have compared blood glucose levels (and other responses) of fasted subjects following consumption of either glucose or trehalose. A consistent finding of these studies was that trehalose ingestion results in a significantly lower blood glucose peak when compared to ingestion of glucose. Crucially, not only were the initial spikes lower but the incremental area under the curve was also significantly reduced.15,16 Trehalose can inhibit glucose transport through solute carrier 2A (SLC2A) transporters with a half-maximal inhibitory concentration (IC50) of 17.3–73.1 mM (SLC2A1–4).17 This could partially account for the observed reduction in blood glucose levels. Paradoxically, if trehalose were efficiently converted to glucose by the brush border trehalase, these glucose molecules would be available to uninhibited SLC2A transporters further along the small intestine. It is likely therefore that not all of the trehalose is hydrolyzed to glucose and absorbed but rather an undetermined amount remains in the lumen where it is available for microbial fermentation. Indeed, this hypothesis is supported by data demonstrating microbial detection of trehalose in the ceca of mice fed trehalose (but not those given water) and in the ileostomy effluent of patients consuming their normal diet.
Trehalose in food may be contributing to the global Clostridium difficile epidemic.
Collins et al., 2019 (3):
Two epidemic ribotypes of Clostridium difficile, RT027 and RT078, have evolved novel methods to metabolise low levels of trehalose.
The ability of RT027 and RT078 strains to metabolize very low concentrations of trehalose, not detected by other ribotypes, provides a competitive advantage to these strains, potentially helping drive their prevalence clinically.
Conclusions: should you take Saccharomyces boulardii?
So, should you take Saccharomyces boulardii as a probiotic or is it useless? On one hand, there are studies that show the efficacy of Saccharomyces boulardii. On the other hand, bile salts in the intestine will quickly wipe out Saccharomyces boulardii cells. If you do not perceive any apparent benefits from taking Saccharomyces boulardii, poor resistance of this yeast to bile acids may be one explanation.
If you need help with a better use of probiotics, or with improving your digestive health in general, do not hesitate to get in contact with us.
Selected references:
1. Martins FS, Miranda IC, Rosa CA, Nicoli JR, Neves MJ. Effect of the trehalose levels on the screening of yeast as probiotic by in vivo and in vitro assays.Braz J Microbiol. 2008;39(1):50-55.
2. Luyckx J, Baudouin C. Trehalose: an intriguing disaccharide with potential for medical application in ophthalmology. Clin Ophthalmol. 2011;5:577-581.
3. Collins J, Danhof H, Britton RA. The role of trehalose in the global spread of epidemic Clostridium difficile. Gut Microbes. 2019;10(2):204-209.