Saccharomyces boulardii

What it is

S. boulardii is a probiotic yeast, not a bacterium, closely related to baker's yeast. It was described by French microbiologist Henri Boulard in 1920 after noticing that people drinking a decoction of lychee and mangosteen skins did not develop diarrhoea.

What the research says

Pooled trials suggest it reduces antibiotic-associated diarrhoea (from 18.7% to 8.5%), but a well-run German hospital trial found no benefit, and against C. difficile the pooled benefit was significant only in children. Its main harm is fungaemia (yeast in the blood), especially in people with central lines, the critically ill or immunocompromised; Europe's medicines regulators contraindicate it for those patients.

Evidence grade: Limited evidence.

What goes wrong

Across 5 Finnish university hospitals over 10 years, at least 20 of 46 patients with Saccharomyces fungaemia were taking S. boulardii; use was 14 times more common than in bacteraemia or candidaemia controls. (Source 1)

• Case-control study, Low certainty.
• Size: 46 fungaemia patients; control group with bacteraemia or candidaemia.
• Who: Hospital patients in Finland, 2009-2018.
• How long: 10 years.
• Result: OR 14 (95% CI 4–44)
• Funding: Not stated in recorded text.

We found 46 patients who had Saccharomyces fungemia; at least 20 (43%) were using S. boulardii probiotic.

The Finnish authors note S. boulardii probiotics are not recommended for patients with indwelling catheters, the immunocompromised or the critically ill. (Source 1)

• Case-control study, Low certainty.
• Size: n/a.
• Who: Patients with catheters, immunocompromise, critical illness.
• How long: n/a.
• Result: n/a.
• Funding: Not stated.

S. cerevisiae var. boulardii probiotics are not recommended for patients who have indwelling catheters, are immunocompromised, or are critically ill.

Position: the EU medicines regulators (CMDh, 2017) recorded 61 cumulative fungaemia reports and contraindicated S. boulardii medicines in critically ill or immunocompromised patients. (Source 2)

• Official position, Certainty not rated.
• Size: 61 cumulative pharmacovigilance cases.
• Who: Users of S. boulardii medicinal products.
• How long: Cumulative to 2017.
• Result: 19 interval cases, 61 cumulative.
• Funding: Regulatory.

critically ill patients or immunocompromised patients due to a risk of fungaemia (see section 4.4).

Class caution: in the PROPATRIA trial of 298 patients with predicted severe acute pancreatitis, a multispecies probiotic given enterally did not reduce infections and more patients died (24 (16%) vs 9 (6%)); the product was a different multispecies mix, so this is a warning about critically ill patients, not evidence about this strain. (Source 3)

• Randomized trial, Moderate certainty.
• Size: 296 analysed (152 probiotic, 144 placebo)
• Who: Adults with predicted severe acute pancreatitis in Dutch hospitals.
• How long: 28 days of treatment; 90-day follow-up.
• Result: Deaths 24 (16%) vs 9 (6%); relative risk 2·53, 95% CI 1·22–5·25.
• Funding: Not stated in recorded text.

24 (16%) patients in the probiotics group died, compared with nine (6%) in the placebo group (relative risk 2·53, 95% CI 1·22–5·25)

In a study of people and mice given antibiotics, a multi-strain probiotic delayed the return of the person's own gut bacteria compared with no treatment; this was a small mechanistic study of one multi-strain product, not of this strain specifically. (Source 4)

• Randomized trial, Low certainty.
• Size: Small human cohort plus mice (exact numbers not in abstract text recorded)
• Who: Healthy human volunteers and mice after broad-spectrum antibiotics.
• How long: Weeks of follow-up after antibiotics.
• Result: Qualitative: 'markedly delayed and persistently incomplete' microbiome reconstitution with probiotics versus spontaneous recovery.
• Funding: Not stated in recorded text.

Compared to spontaneous post-antibiotic recovery, probiotics induced a markedly delayed and persistently incomplete indigenous stool/mucosal microbiome reconstitution

What the evidence supports

Pooled trials found S. boulardii reduced antibiotic-associated diarrhoea from 18.7% to 8.5%. (Source 5)

• Meta-analysis, Moderate certainty.
• Size: 21 RCTs (about 4,780 participants; children n=1653, adults n=3114 per the abstract)
• Who: Children and adults taking antibiotics.
• How long: Varied.
• Result: RR 0.47; 95% CI 0.38-0.57; NNT 10.
• Funding: Not stated in recorded text.

Administration of S. boulardii compared with placebo or no treatment reduced the risk of antibiotic-associated diarrhoea (as defined by the study investigators) in patients treated with antibiotics from 18.7% to 8.5%

What the evidence does not support

In a German hospital trial, S. boulardii did not prevent antibiotic-associated diarrhoea compared with placebo (21 vs 19 cases). (Source 6)

• Randomized trial, Moderate certainty.
• Size: 477 randomised (246 active, 231 placebo)
• Who: Hospitalised adults on systemic antibiotics.
• How long: Course of antibiotics plus follow-up.
• Result: HR 1.02 (95% CI .55–1.90; P = .94)
• Funding: Not located in fetched text.

we found no evidence for the efficacy of the tested S boulardii regimen to prevent AAD in a population of hospitalized patients who received systemic antibiotic treatment.

Where the evidence is mixed

For C. difficile diarrhoea, the pooled reduction with S. boulardii was significant in children but not in adults. (Source 5)

• Meta-analysis, Low certainty.
• Size: Children 2 trials (n=579); adults 9 trials (n=1441)
• Who: Children and adults taking antibiotics.
• How long: Varied.
• Result: Children RR 0.25 (0.08-0.73); adults RR 0.8 (0.47-1.34)
• Funding: Not stated in recorded text.

this reduction was significant only in children (2 randomised controlled trials, n = 579, RR: 0.25; 95% CI: 0.08-0.73) and not in adults (9 randomised controlled trials, n = 1441, RR: 0.8, 95% CI: 0.47-1.34)

Where the research disagrees

Does S. boulardii prevent antibiotic-associated diarrhoea?

• Szajewska and Kołodziej 2015 meta-analysis, meta-analysis of 21 RCTs: This meta-analysis confirms that S. boulardii is effective in reducing the risk of antibiotic-associated diarrhoea in children and adults. (Source 5)
• Ehrhardt et al. 2016, double-masked RCT, 477 hospitalised adults: In conclusion, we found no evidence for the efficacy of the tested S boulardii regimen to prevent AAD in a population of hospitalized patients who received systemic antibiotic treatment. (Source 6)

How much

• Reference intake: No recommended intake exists; S. boulardii is not a nutrient. The EU regulatory position concerns contraindications, not intake. (Source 2)
• Upper limit: No upper limit has been set. The EU regulators instead contraindicate use in critically ill or immunocompromised patients. (Source 2)
• Studied: The German hospital trial gave Perenterol forte 250 mg capsules twice daily. (Source 6)

A common belief, and what the research shows

The belief: A probiotic yeast is harmless because it is just a relative of baker's yeast.

What the research shows: Finnish hospital data found 'at least 20 (43%) were using S. boulardii probiotic' among 46 fungaemia patients, and EU regulators contraindicate it in 'critically ill patients or immunocompromised patients due to a risk of fungaemia (see section 4.4).'

Questions and answers

What is it?

S. boulardii is a probiotic yeast related to baker's yeast. It was described in 1920 by Henri Boulard, who noticed people drinking a lychee and mangosteen skin decoction did not get diarrhoea. (Source 7)

What does it do in the body?

Lab and animal work on one strain, CNCM I-745 (reviewed by an author who has consulted for and been funded by its maker), suggests it acts on bacterial toxins, pathogens and the gut lining. In people, pooled trials show fewer cases of antibiotic-associated diarrhoea, though not every trial agrees. (Source 7)

Is it good or bad for you?

Depends on who takes it. Pooled trials suggest benefit for antibiotic-associated diarrhoea, but it can cause bloodstream yeast infection in vulnerable patients, especially those with catheters, critical illness or weak immunity. (Source 1)

How do you get more of it?

In trials, people took it as capsules, for example Perenterol forte 250 mg (at least 1.8 × 10¹⁰ live cells per gram of freeze-dried powder) twice daily in a German hospital trial. This describes what was studied only. (Source 6)

If it is harmful, what reduces it?

When it causes fungaemia, the linked factor is probiotic use itself; the Finnish study found users far more common among fungaemia patients. Treatment of an infection is a medical matter not covered by our sources. (Source 1)

Why might someone be low in it or missing it?

It is not a normal resident of the human gut; people only have it when they take it. Antibiotics disturb gut bacteria, which is why it is often taken with them. (Source 4)

Which whole foods contain it or feed it?

No modern food source was found in our search. Its origin story involves a lychee and mangosteen skin decoction, but that is history, not evidence that these fruits supply it. (Source 7)

What happens if you do not have it?

Nothing is known to go wrong from not having it, since it is not a normal gut resident. (Source 7)

We searched: Searched for consequences of absence; none exist in the literature we retrieved. Closest source is the Czerucka 2019 review.

How can you test for it?

No test for carrying it in the gut is used routinely. In hospitals, Saccharomyces is found by blood or other clinical cultures, as in the Finnish study. (Source 1)

References

1. Emerging Infectious Diseases (CDC). Fungemia and Other Fungal Infections Associated with Use of Saccharomyces boulardii Probiotic Supplements. 2021. DOI 10.3201/eid2708.210018. Read the source
2. European Medicines Agency / CMDh. Saccharomyces boulardii: CMDh scientific conclusions and grounds for the variation, amendments to the product information (PSUSA/00009284/201702). 2017. Read the source
3. The Lancet. Probiotic prophylaxis in predicted severe acute pancreatitis: a randomised, double-blind, placebo-controlled trial. 2008. PMID 18279948, DOI 10.1016/S0140-6736(08)60207-X. Read the source
4. Cell. Post-Antibiotic Gut Mucosal Microbiome Reconstitution Is Impaired by Probiotics and Improved by Autologous FMT. 2018. PMID 30193113, DOI 10.1016/j.cell.2018.08.047. Read the source
5. Alimentary Pharmacology & Therapeutics. Systematic review with meta-analysis: Saccharomyces boulardii in the prevention of antibiotic-associated diarrhoea. 2015. PMID 26216624, DOI 10.1111/apt.13344. Read the source
6. Open Forum Infectious Diseases. Saccharomyces boulardii to Prevent Antibiotic-Associated Diarrhea: A Randomized, Double-Masked, Placebo-Controlled Trial. 2016. PMID 26973849, DOI 10.1093/ofid/ofw011. Read the source
7. World Journal of Gastroenterology. Diversity of Saccharomyces boulardii CNCM I-745 mechanisms of action against intestinal infections. 2019. DOI 10.3748/wjg.v25.i18.2188. Read the source