Is Saccharomyces boulardii effective in the treatment of diarrhea?

What is Saccharomyces boulardii?

Saccharomyces boulardii is a probiotic, specifically a type of beneficial nonpathogenic yeast.

What are the benefits of Saccharomyces boulardii?

• Saccharomcyes boulardii has been used in clinical practice for over 30 years for the management of diarrheal diseases [1]
• Saccharomyces has demonstrated clinical and experimental benefits in gastrointestinal diseases – particularly those with an inflammatory component [1]
• The presumed benefit of Saccharamocyes in gastrointestinal diseases is the ability of the yeast to mimic the protective effects of the normal, healthy gut microbiota [1]
• Overall –research has demonstrated limited strong indications for use of probiotics in the general healthy population. However, there is fairly strong evidence to support the use of probiotics (specifically Saccharomyces) for the management of C. diff and antibiotic associated diarrhea.

Mechanisms of Action: How does Saccharomyces work?

• Has a role in the regulation of intestinal microbial homeostasis [1]
• Interferes with the ability of pathogens to colonize and infect the mucosa [1]
• Modulates local and systemic immune responses [1]
• Stabilizes the gastrointestinal barrier function and induces digestive enzyme activity, which assists with the absorption of nutrition [1]

What is C. Diff? 

Clostridiodes difficile (formerly known as Clostridium difficile) and a bacteria that causes diarrhea and colitis (inflammation of the colon). C. diff infection most often occurs during or following a course of antibiotic treatment. 

Other risk factors for C. diff include: 

• >65 years of age
• Weakened immune system
• Recent hospitalization
• Previous C. diff infection 
  • ~20% of patients with C. diff have a recurrence, and these patients tend to have ongoing recurrences [2]. This pattern of repeated recurrences can persist for up to 4 years, regardless of subsequent antibiotic regimens. Recurrent episodes of C. diff are debilitating and expensive [2]. 

Symptoms of C. diff include: 

• Frequent diarrhea
• Fever
• Abdominal pain
• Nausea
• Loss of appetite

Evidence to support the use of Saccharomcyes boulardii in Antibiotic-Associated Diarrhea (AAD):

• A meta-analysis of 10 RCT’s in adults demonstrated that Saccharomyces boulardii was significantly protective for AAD [3]
  • The protective effect of S. boulardii and the significant relative reduction in AAD compared to control groups ranged between 7.4% and 25% [3]
• Recent meta-analysis of 21 RCTs demonstrated that administration of S. boulardii reduced risk of AAD in patients receiving antibiotics from 18.7% to 8.5% [4]

Evidence to support the use of Saccharomcyes boulardii in C. Diff:

• A meta-analysis of 31 randomized controlled trials demonstrated moderate certainty evidence that probiotics are effective for preventing CDAD 
  • Complete case analysis among trials investigating CDAD suggests that probiotics reduce the risk of CDAD by 60%. The incidence of CDAD in adult and children receiving antibiotic therapy was 1.5% in the probiotic group compared to 4.0% in the placebo or no treatment control group [5]
• A meta-analysis of six RCTs of different probiotics (including S. boulardii), showed that probiotics had a significant efficacy to prevent subsequent recurrences of CDI (RR = 0.59, 95% CI 0.41-0.85, p = 0.005) [3]
  • S. boulardii is the most effective probiotic for prevention, or in combination with other agents, treatment of AAD and recurrent CDI [3]
  • Two RCTs demonstrated significant relative reduction of recurrent CDI (19% and 33.3%) in adults taking S. boulardii [6; 2] 

Evidence to support the use of Saccharomcyes boulardii in C. Diff (Probiotic + Antibiotic Combination Treatment):

• Two RCTs investigated the efficacy of a combination treatment of S. boulardii with an antibiotic (vancomycin or metronidazole) for patients with C. diff-associated disease (CDD) [6;2]
  • Multivariate analysis showed that patients treated with S. boulardii as well as standard antibiotics had a significantly lower relative risk (RR) of CDD recurrence compared with placebo and standard antibiotics [6]
  • Results were significant for patients with recurrent CDD; no benefit was demonstrated for patients with an initial episode of CDD [6]
  • A significant decrease in recurrences of CDD was observed in patients treated with high-dose vancomycin (2g/day) as well as S. boulardii (16.7% recurrence) compared to those receiving high-dose vancomycin and placebo (50%) [2]

Other Potential Indications for Use of Saccharomyces boulardii: [1]

• Persistent diarrhea 
• Acute diarrhea 
• Enteral nutrition-related diarrhea 
• Traveler’s diarrhea
• H. pylori infection 
• Crohn’s disease
• Ulcerative colitis
• Irritable bowel syndrome
• Parasite infections
• HIV-related diarrhea

Contraindications:

Probiotics, including Saccharomyces boulardii, are generally considered low risk and safe for use in immunocompetent subjects [1]. If you are immunocompromised, have severe intestinal disease, or an indwelling catheter, discuss the use of a probiotic with your physician before starting to take it. 

References

1. Kelesidis, T. & Pothoulakis, C. (2012). Efficacy and safety of the probiotic Saccharomyces boulardii for the prevention and therapy of gastrointestinal disorders. Ther Adv Gastroenterol, 5(2), 111-125. 
2. Surawicz, C.M., McFarland, L.V., Greenberg, R.N., Rubin, M., Fekety, R., Mulligan, M.E. et al. (2000). The search for a better treatment for recurrent Clostridium difficile disease: use of high-dose vancomycin combined with Saccharomyces boulardii. Clin Infect Dis, 31, 1012–1017.
3. McFarland, L.V. (2010). Systematic review and metaanalysis of Saccharomyces boulardii in adult patients. World J Gastroenterol, 16, 2202–2222. 
4. Szajewska, H. & Kotodziej, M. (2015). Systematic review with meta-analysis: Saccharomyces boulardii in the prevention of antibiotic-associated diarrhea. Aliment Pharmacol Ther, 42, 793-801. 
5. Goldenberg, J.Z., Yap, C., Lytvyn, L., Lo, C.K.F., Beardsley, J., Mertz, D. & Johnston, B.C. (2007). Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children (review). Cochrane Database of Systematic Reviews, 12, 1-152.
6. McFarland, L.V., Surawicz, C.M., Greenberg, R.N., Fekety, R., Elmer, G.W., Moyer, K.A. et al. (1994). A randomized placebo-controlled trial of Saccharomyces boulardii in combination with standard antibiotics for Clostridium difficile disease. JAMA, 271, 1913–1918.