Saccharomyces Boulardii: The Antibiotic Resistant Probiotic

Like many people, I came across Saccharomyces boulardii (S. boulardii) while I was forced to take a course of antibiotics. As I began to do my research, I realized that this crazy little probiotic yeast is one of the most proven supplements on the market today, with hundreds of peer reviewed studies proving efficacy in a number of different contexts.

Note for commenters: our founder John is helping out on this post.

S. Boulardii and Candida

I am going to do a thorough break down of S. boulardii’s benefits in a moment, but one of the most interesting for me is S. boulardii’s ability to beat back Candida.

Candida is a pathogenic yeast that is found in everyone’s intestinal tract, but it can run amuck and proliferate beyond healthy levels when our gut flora is disturbed, as it can be when we’re drinking a lot, or after a course of antibiotics has disrupted the normal microbial balance in the gut.

S. boulardii has been shown effective at killing Candida, and suppressing expression of the inflammatory markers it produces. ¹²

S. boulardii basics

S. boulardii is a non-pathogenic yeast microbe that has been proven in multiple randomized clinical studies to be an effective probiotic, especially in the treatment of antibiotic induced diarrhea, traveler’s diarrhea, and other inflammatory bowel conditions. S. boulardii has even been shown to increase serum IgA levels in mice which has led researchers to speculate that S. boulardii may have potential for boosting the strength of the human immune system.

Because S. boulardii is a yeast microbe, it is not killed by antibiotics, and can be taken directly alongside a course of antibiotics.³ So, how did S. boulardii come to be used as a dietary supplement?

The story starts in French colonial days. 

History of Saccharomyces boulardii

The French scientist Henry Boulard first discovered S. boulardii in 1920 after observing that certain locals in Indonesia were not succumbing to an outbreak of cholera. The healthier locals drank a tea made from the skins of lychee and mangosteen, from which Boulard was able to isolate S. boulardii as the protective yeast. The strain has been named after him ever since its discovery. 

S. boulardii survives the digestive tract to reach the colon and confer benefit

One of the knocks on some supplements is lack of bioavailability. For example, the bioavailability of curcumin has always been an issue.⁴ Some say that if nutrients, like curcumin, could be delivered intact through the digestive tract, they could deliver a benefit, but our digestion destroys the nutrients before delivery.

This is not the case with S. boulardii.

To be effective, a probiotic must survive the gauntlet of the digestive system to arrive intact when it reaches the colon, which is why the World Health Organization defines probiotics as “live microorganisms which when administered in adequate amounts confer a health benefit on the host.” In the case of lyophilized oral administration, as much as 3% of the living yeast of S. boulardii can be recovered in the fecal matter of recipients. This proves that S. boulardii survives the gastric acidity of our digestive tract. To quote this meta analysis of S. boulardii studies that appeared in the World Journal of Gastroenterology:

Organisms need to survive at body temperature (37°C), be resistant to stomach acids and bile acids, and exist in the competitive milieu of the intestinal tract. Probiotic strains of Saccharomyces have been shown to have these abilities. Although the optimal temperature for most strains of Saccharomyces range from 22-30°C, S. boulardii survives best at 37°C, giving it a unique advantage of being one of the few yeasts that do best at human body temperatures.

S. boulardii cannot be killed by antibiotics

As new research emerges about the importance of the health of our gut to our overall health, more and more people look for ways to guard against damage to their intestinal flora when they are forced to take a course of antibiotics.

While it may still be worthwhile to take some bacteria based probiotics during a course of antibiotics, the antibiotics will kill the good with the bad, eliminating much of the value in a traditional probiotic. By contrast, S. boulardii is a yeast microbe, and as such, is immune to antibiotics. Antibiotics do not kill S. boulardii and S. boulardii can even be taken at the exact same time as a course of antibiotics.⁵

S. boulardii treats antibiotic associated diarrhea

As the name suggests, antibiotic associated diarrhea (AAD) is the problem of diarrhea as a side effect of taking antibiotics. AAD symptoms can range from mild to more severe (colitis) and can even result in death. ⁶ The problem is especially prevalent in hospital patients, but varies by the type of antibiotic.

AAD can be divided between late (diarrhea begins after antibiotic course ends) and early onset, with the timing of symptoms varying by the type of antibiotic. Early onset of AAD was associated with clindamycin, amoxicillin and ampicillin, while delayed-onset AAD was associated with erythromycin, ciprofloxacin and clarithromycin.

Clostridium difficile disease

Clostridium difficile disease (CDD) is one of the most prevalent, and contagious, forms of AAD. CDD is nasty, and potentially fatal.⁷ In fact, repeated CDD infections are sometimes treated with Fecal transplant procedures, including at world renowned hospitals like the Mayo Clinic. Studies have shown that S. boulardii is the only effective probiotic in preventing CDD. Click here for the study.

CDD produces two exotoxins (toxin A and B) that suppress immune function. The extent to which patients have severe CDD symptoms is a function of the level of IgA and IgG antibodies they produce in reaction to those exotoxins. The greater the antibodies, the less severe their CDD symptoms.

Why is S. boulardii so effective at preventing CDD?

It seems to strengthen the immune system’s response to CDD. Studies in both rats and mice have shown S. boulardii to increase levels of immune system boosting IgA and IgG antibodies, which are the crucial metric in determining the severity of a bout of CDD. ⁸

To quote one such study:

High titers of serum or intestinal antibodies against toxin A have been associated with asymptomatic carriage of toxigenic CDD and with shorter and less severe episodes of CDD.

S. boulardii may help prevent traveler’s diarrhea

In addition to its important role in preventing incidents of CDD, S. boulardii has been proven to help prevent the occurrence of traveler’s diarrhea.

This is a big one for me when I’ve traveled to Asia. You want to jump right in and enjoy everything the locals do “Anthony Bourdain” style, but you also fear spending a large chunk of the trip in the bathroom.

This meta-analysis of studies found that probiotics, and especially S. boulardii, “significantly prevent traveler’s diarrhea.” 

S. boulardii and helicobacter pylori infection

Helicobacter pylori infection (H. pylori) is a stealth bacteria that is almost unbelievably common worldwide, with an estimated 50% of the world’s population infected. ^{9 10} Although it can cause stomach ulcers and other symptoms, many people never know they have it.

H. pylori infection has been shown to increase the risk of gastric cancer by as much as 8 times. ¹¹ From where I’m sitting, it’s amazing that H. pylori isn’t on more people’s radars. I was surprised to learn that in addition to its link to stomach cancer, it’s contagious, huge percentages of undeveloped countries carry the bug (as high as 80% in rural India), and it can cause an increase in LDL. ^{1213 14}

I’d heard very little about H. pylori until I started researching S. boulardii, and learned that S. boulardii can help mitigate some damage caused by H. pylori, especially AAD caused by the standard antibiotic treatment regimen.

Patients receiving antibiotics to treat H. pylori infection had significantly lower incidents of AAD when taking S. boulardii. ¹⁵

Interestingly, this study hinted at the possibility that S. boulardii may “induce morphologic changes in H. pylori cells consistent with cellular damage.” Further research is needed to determine whether S. boulardii can in fact kill, or alter, H. pylori.

S. boulardii and treatment of chronic diseases

Crohn’s disease

S. boulardii was shown to help Crohn’s disease patients stay in remission, as well as improve measures of intestinal permeability, otherwise known as leaky gut.¹⁶

Irritable bowel syndrome

For more on IBS, see the podcast John did with Joel Evans, MD on using the latest technology in food sensitivity testing to help alleviate IBS.

S. boulardii supplementation improved quality of life for IBS patients, but not bowel frequency or stool consistency.¹⁷

This meta-analysis found that, when compared with placebo, probiotics improved global IBS symptoms as well as reduced abdominal pain in IBS patients.¹⁸

S. boulardii benefits in healthy people

In those struggling with AAD, we know that S. boulardii plays an important role in bolstering the immune system against exotoxins. What is the mechanism for action in healthy people?

This study essentially found that intestinal inflammation makes it easier for S. boulardii to do its work, since the breakdown in the intestinal lining helps it reach immune cells. However, in a healthy intestine, the mechanism of action is likely not immune-mediated. Instead, it looks like S. boulardii helps in maintaining a healthy bacterial state in the gut (i.e. S. boulardii acts as a microbiome fertilizer allowing healthy bacteria to flourish and crowding out more damaging strains), and by strengthening epithelial integrity, basically keeping the gut lining strong and preventing leaky gut. ¹⁹

Saccharomyces boulardii and your genes

Above I’ve discussed a wide range of health improvements linked with S. boulardii. Yet an important question remains about the potential genetic contributions to the various disorders mentioned above.

Understanding digestive health and its interaction with allergies is a highly complex area, and so it can be difficult to identify genes which might play a role. However, in the more serious disorders such as Crohn’s disease, there are a few genes of interest that keep appearing.

NOD2

NOD2, or Nucleotide-binding oligomerization domain-containing protein 2 to give it its full name has a strong association with Crohn’s and IBD. So strong in fact that when it was first discovered it was named IBD1, or inflammatory bowel disease protein 1. NOD2 is a receptor protein which is expressed in the lining of the gut, it recognizes bacterial molecules and stimulates an immune response.

Two SNPs within NOD2 have been described which display a strong association with the development of Crohn’s. rs2066844 or C2023T which describes a change from a ‘C’ allele to a ‘T’ allele in approximately 2% of the population. Secondly, rs2066845 or G722C which describes a change from a ‘G’ to a ‘C’ allele in less than 1% of the population.²⁰²¹ Both of these SNPs induce a change in the protein structure of NOD2, which leads to an increased susceptibility to developing Crohn’s disease, although the authors of the report do not confirm a methodology.

It is however possible to hypothesize that NOD2 produced by the risk ‘T’ allele of rs2066844 C2023T, or the risk ‘C’ allele of rs2066845 G722C is either more sensitive to bacteria, or is present in greater amounts, meaning that it more easily stimulates an immune response.

IL23R

The second gene of interest is interleukin 23 receptor or IL23R. As its name suggests IL23R is the receptor protein for IL-23. IL-23 is a molecule which is released by immune cells when they detect a bacterial pathogen, which acts to stimulate the recruitment of other immune cells and generates an immune response. So it’s fairly easy to see how this could play a role in the development of Crohn’s disease.

Sure enough, there are two SNPs both of which are associated with an increased risk of developing Crohn’s. rs1004819 or G653-2380A which leads to the change of a ‘G‘ allele to an ‘A’ allele in approximately %40 of people. And also rs2201841 or A956-8194G which leads to the change of an ‘A’ allele into a ‘G‘ allele also in about 40% of the population.

As above the mechanism by which these two SNPs increase the risk of developing Crohn’s is poorly understood, however there is a significant association between them.²² It is possible that a similar effect as was hypothesized for NOD2 is occuring, where a more sensitive form of IL23R is produced by those carrying the risk ‘G‘ allele of either rs1004819 G653-2380A or rs2201841 A956-8194G. This more sensitive IL23R may then induce an immune response and inflammation much more readily than the normal form.

Tying it back to S. boulardii 

There are have been no studies directly looking at S. boulardii in relation to these, or any other SNPs, although a beneficial effect for Crohn’s in general has been described.²³ However, it is easy to see how the beneficial effects described above would be helpful for those at risk of developing Crohn’s. By promoting a healthy gut flora S. boulardii may reduce the chance of the sensitive NOD2 or IL23R proteins, in those carrying the risk allele, being stimulated thus preventing the generation of an immune response.

Bottom line

The bottom line with S. boulardii is that it’s a proven supplement that has been shown the greatest efficacy in helping people with compromised gut health crowd out the “bad guys” so the “good guys” have a chance to flourish once again.