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Saccharomyces boulardii – a key

probiotic in clinical practice

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Joanna Scott-LutyensBA(Hons) DipION FdSc

Nutritional Therapist

#optibacwebinar

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Agenda

• Introduction to Saccharomyces boulardii

• Methods of action

• The clinical research and use of S. boulardii in clinic

• Protocol

#optibacwebinar

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Many bacteria species and strains Only 1 yeast strain is a probiotic

Probiotics definition

Pro (pro) = « in favor of »

Biotics (biotic) = « life »

“Live microorganisms which when administered in adequate

amounts confer a health benefit on the host”

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Bacteria vs. Yeast

Bacteria

• Prokaryotic cells (DNA strands)

• Sensitive to antibiotics

• Replicate by division

• Divides every 20-30 min

Yeast

• Eukaryotic cell (nucleus)

• Insensitive to antibiotics

• Sensitive to anti-fungal agents e.g. garlic

• Replicates by budding

Division Budding

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S. boulardii: the only ONE probiotic yeast

• Henri Boulard discovered it in

1923

• On tropical fruits peel (lychee)

in Vietnam

• The peel was used by natives

against diarrhea, especially in

those afflicted with cholera

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Taxonomy / Identity

• S. cerevisiae vs. S. boulardii

– Can be sometimes confusing because they both have similar names

– S. cerevisiae = Baker’s and Brewer’s yeast

• Complete scientific name are as follows:

– S. cerevisiae = Saccharomyces cerevisiae

– S. boulardii = Saccharomyces cerevisiae var boulardii

However there are many differences

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Survival in the gastrointestinal tract

• Achieve high concentration in the colon quickly

• Transient - does not permanently colonise the colon

• In human volunteers, the maximum stool concentration is

reached 36-60 hours

• Eliminated within 2-5 days

• Naturally resistant to antibiotics

• Sensitive to non absorbable anti-fungi (e.g. Nystatine)

(L.V Mc Farland et al(1993), S.boulardii : A review of an innovative Biotherapeutic agent. Microbial Ecology in Health

and Disease 6:157-171) Boddy et al, Influence of antibiotics on the recovery and kinetics of S.boulardii in rats.

Pharmaceutical Research 1991, Bléhaut et al, Disposition Kinetics of S.boulardii in man and rat.1989

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Mechanisms of action

1. Binding of enterohaemorrhagic E. coli and Salmonella

2. Protection against toxins in the gut lumen

3. Favour growth of lactic acid bacteria e.g. Lactobacillus spp

4. Reinforces the integrity of the mucosal lining

5. Increases surface area in the gut

6. Increases brush border enzymes

7. Stimulates increase in Secretory IgA

8. Acts against Candida albicans

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1. Binding of harmful bacteria such as E. coli and Salmonella

Gedek et al (1989)

S. Boulardii with D-

mannose rich outer

membrane, giving

sticky surface

Many harmful

bacteria stick to

one S. boulardii,

and are removed

from the gut

F1

Slide 10

F1 D-mannose on the outer membrane of the SB sticks to Type I fimbrae of bacteria. Type I fimbrae is present on E. coli, Salmonella, Klebsiella and more... Farah, 31/07/2013

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2. Protection against toxins in the lumen

Clostridium Difficile

� S. boulardii inhibits the effects of C. Diff toxins A and B. S. boulardii releases a 54kDa protease which inactivates toxins A and B and lyses the colonic receptors (Castagliuolo, 1996)

Cholera toxin

� Cholera toxins A and B lead to the activation of cAMP which induces theopening of Cl- channels and closing of Na+/H+ channels and Cl-/HCO3-exchanges. This results in water and electrolyte secretion (Dias, 1995).

� S. boulardii releases a 120kDa protein which stimulates antisecretory factors resulting in a down-regulation of cAMP.

E. Coli

� S. boulardii produces a protein phosphatase. This dephosphorylates endotoxins such as E. Coli LPS, altering its binding site and partially inactivating cytotoxic effects (Buts, 2006).

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3. Favour growth of lactic acid bacteria

Gedek et al (1999)

Ménard S et al (2004)

F2

Slide 12

F2 Although SB itself just acts as a cleanse by removing harmful bacteria from the system there is less competition for the natural resident friendly bacteria, therefore they are seen to flourish:

This table shows upon supplementation with SB, lactobaccillus levels increased by 100 fold, bifidobacteria by 10 fold and E. coli decreased by around 100 fold.. Farah, 31/07/2013

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4. Reinforces the integrity of the mucosal lining

S. boulardii maintains the

integrity of the gut wall lining

by preserving tight junctions. It

does this preventing the

phosphorylation of MLC

(Myosin Light Chain). The

phosphorylation of MLC is the

first step in the cell signalling

pathway when E.coli and other

harmful bacteria attack tight

junctions.

Wu (2007) Saccharomyces boulardii ameliorates Citrobacter rodentium-induced colitis through actions on

bacterial virulence factors. Am J Physiol Gastrointest Liver Physiol; 294, 1: G295-306.

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5. Increases surface area in the gut

S. boulardii increases the levels of

polyamines – spermine and

spermidine (Buts, 1994).

This leads to cell proliferation

As can be seen as an increase in

villi height and crypt depth, which

gives increased surface area in the

small intestine for improved

absorption of nutrients from the

diet.

Polyamines = group of cell components that are important in the regulation of cell proliferation and cell

differentiation. Polyamine deficiency results in an arrest of cell proliferation, which can be reversed by supplementation with external polyamines. Polyamine deficiency can also, under certain circumstances,

result in programmed cell death or apoptosis

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6. Increases brush border enzymes

“In weanling rats (d 20 to d 30), a daily dose of 100 mg of lyophilized S.

boulardii produced significant (p < 0.025) increases in sucrase (157%) and

maltase (47%) activities.” Buts JP et al (1994)

It’s thought this increase is mediated by Saccharomyces boulardii induced

increase in spermine and spermidine.

S. boulardii has a trophic effect on the gut

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7. Stimulates increase in Secretory IgA

Qamar et al (2001)

Secretory IgA is an immune

factor found in the intestinal

tract, which helps to protect

against harmful pathogens.

F3

Slide 16

F3 Upon supplementation with SB levels of sIgA are greatly increased Farah, 31/07/2013

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How does it work?

– “Crowds out” the candida yeast

– Produces capric, caprylic and caproic acids which inhibits the

adhesion of the candida by destroying the hyphae, and also

prevents the biofilm from forming (Murzyn et al,2010)

8. Acts against Candida albicans

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Mechanisms of action - Overview

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Clinical Applications of S. boulardii

• Diarrhoea

• Candida

• Pathogenic bacteria overgrowth

• Clostridium difficle

• IBD

• IBS

• H. pylori

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Diarrhoea

McFarland L.V., (2010), ‘Systematic review and meta-analysis of Saccharomyces

boulardii in adult patients’. World Journal of Gastroenterology, 16(18):2202–

2222

•Review/Meta analysis of 31 randomised, placebo-controlled treatment arms in 27 trials,

encompassing 5029 study patients

•Found S. boulardii to be significantly effective and safe in 84% of those treatment arms

•Can therefore be strongly recommended for prevention of AAD, as well as for traveller’s

diarrhoea and the prevention of nutrition-related diarrhoea; also for the alleviation

of Helicobacter pylori infection and related symptoms.

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Diarrhoea

Cetina-Sauri, G. & Basto, S., (1994), ‘Therapeutic evaluation

of Saccharomyces boulardii in children with acute diarrhoea’. Annales de

Pediatrie, 41(6):397-400.

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Diarrhoea

• Kurugol & Koturoglu (2005) - 200 children. Duration of diarrhoea reduced (4.7

vs 5.5).

• Wan et al (2017) 408 children. Incidence of diarrhoea less with SB than control

22 vs 57

• Zhang et al (2017) looked at 163 elderly hospitalised patients on antibiotics.

14.8% vs 28.0%

• Kabbani et al (2017)

• Das et al (2016)

• Tung et al. (2009) - Clostridium difficile

• Surawicz (2003) - Clostridium difficile

• Micklefield (2014), Feizizadeh et al (2014) – Reviews

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IBD

‘We know that the possible therapeutic mechanisms of probiotics in intestinal

inflammatory disorders include: antagonism against enteric pathogens;

strengthening of the gut mucosal barrier; inhibition of the local secretion of

inflammatory mediators; and stabilisation of local immunological activity’

(Kelesidis T 2012).

•Guslandi M. et al., (2003) – 25 patients with Ulcerative Colitis. Successful

outcome in 17 out of 25 patients taking SB

•Guslandi et al (2000) – 32 patients with Crohn’s disease – 38% relapsed in

control group compared to the 6% relapse in intervention group

•Plein and Hotz (1993) – 20 patients with Crohn’s disease.

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Candida

Candida is becoming less responsive to some of the antifungals as the biofilm is resistant

to them

Saccharomyces boulardii is becoming a commonly used probiotic used to combat Candida.

S. boulardii secretes capric, caprylic, and caproic acids which inhibit the hyphae formation.

It also reduces Candidial adhesion and biofilm formation. Murzyn et al., (2010)

– Matsubara VH., et al (2016) – A review which discusses the use of SB for Candidais

– Ducluzeau & Bensaada (1982) observed a 90% decrease in Candida albicans when

treated with S. boulardii

– Berg et al (1993) found S. boulardii decreased the incidence of C. albicans

translocation

– Jawhara, S. & Poulain, D. (2007) found S. boulardii decreased inflammation and C.

albicans colonisation

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IBS

IBS can be caused by several of the imbalances that Saccharomyces boulardii can

help combat – such as pathogenic bacteria overgrowth, inflammation, candida.

S. boulardii may therefore be applicable for IBS

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H. Pylori

•S. boulardii as a useful as an adjuvant to antibiotics.

•Protects against side effects and therefore improves compliancy

•Increases eradication rate

Homan & Orel (2015) Found S. boulardii to be an effective adjuvant to antibiotic

treatment of H. Pylori

Namkin et al., (2016) looked at S. boulardii eradication of H. Pylori in 28 children

in Iran – helped increase the eradication of H. Pylori but not as a single therapy

Bin et al., (2015) 194 H. Pylori positive children. Reduced incidence of side effects

of triple therapy and slightly increased rate of eradication

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• 5 billion per capsule

• Dairy free

• Free of excipients

• Packs of 14, 40, 80

• 8 mechanisms of action

• Can be taken alone, or in combination

Product specifications

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Saccharomyces boulardii protocol

• 1-6 capsules a day depending on severity of symptom.

• Severe diarrhoea – start with 6 then reduce as symptoms clear

• Candida – start with 2, increase to 4 or 6 until symptoms clear

• Additionally, take a regular probiotic (such as For every day EXTRA Strength) to

repopulate gut as it’s being cleared

• Take away from any other anti-microbial

• Consult doctor if pregnant or breast-feeding

• General diet – especially with IBS, IBD and Candida

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https://www.probioticsdatabase.co.uk

Probiotics Database

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Thank you for your attentionjoanna@wrenlabs.com

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References

• Bin, Z., et al. (2015). The Efficacy of Saccharomyces boulardii CNCM I-745 in Addition to Standard Helicobacter pylori Eradication Treatment in

Children. Pediatric Gastroenterology, Hepatology & Nutrition, 18(1), 17–22.

• Berg, R. et al. (1993) Inhibition of Candida albicans translocation from the gastrointestinal tract of mice by oral administration of Saccharomyces boulardii. J

Infect Dis. Nov;168(5):1314-8.

• Buts JP, et al. (2006) Saccharomyces boulardii produces in rat small intestine a novel protein phosphatase that inhibits Escherichia coli endotoxin by

dephosphorylation. Pediatr Res. Jul;60(1):24-9.

• Buts JP et al (1994) Saccharomyces boulardii enhances rat intestinal enzyme expression by endoluminal release of polyamines. Pediatr Res. Oct;36(4):522-7.

• Castagliuolo, I. et al (1996). Saccharomyces boulardii protease inhibits Clostridium difficile toxin: An effect in the rat ileum. Infect Immun., 64 : 5225-5232

• Cetina-Sauri, G. & Basto, S., (1994), ‘Therapeutic evaluation of Saccharomyces boulardii in children with acute diarrhea’. Annales de Pediatrie, 41(6):397-400.

• Das S, et al. (2016) Efficacy and Safety of Saccharomyces boulardii in Acute Rotavirus Diarrhea: Double Blind Randomized Controlled Trial from a Developing

Country. J Trop Pediatr. Dec;62(6):464-470

• Demirel, G., et al., (2013), ‘Prophylactic Saccharomyces boulardii versus nystatin for the prevention of fungal colonization and invasive fungal infection in

premature infants’. Eur. J. Pediatr., 172:1321.

• Dias, R.S., et al (1995). Protective effect of Saccharomyces boulardii against the cholera toxin in rats. Braz. J. Med. Biol. Res. 28: 323- 325.

• Ducluzeau, R. & Bensaada, M. (1982) Comparative effect of a single or continuous administration of Saccharomyces boulardii on the establishment of various

strains of candida in the digestive tract of gnotobiotic mice. Annales de microbiologie. (Inst. Pasteur). 133: pp: 491-501

• Feizizadeh S, et al (2014) Efficacy and safety of Saccharomyces boulardii for acute diarrhea. Pediatrics. 2014 Jul;134(1):e176-91. doi: 10.1542/peds.2013-3950.

Review.

• Gedek B. (1989). Intestinal flora and bioregulation. Bull. Sci. Tec. Off. Inter. Epizoot., 8, 417- 433.

• Guslandi M, et al. (2000) Saccharomyces boulardii in maintenance treatment of Crohn's disease. Dig Dis Sci; 45: 1462-1464

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• Guslandi M. et al., (2003), ‘A pilot trial of Saccharomyces boulardii in ulcerative colitis’. European Journal of Gastroenterology & Hepatology. 15:697-698.

• Homan, M., & Orel, R. (2015). Are probiotics useful in Helicobacter pylori eradication? World Journal of Gastroenterology : WJG, 21(37), 10644–10653.

• Jawhara, S. & Poulain, D. (2007) Saccharomyces boulardii decreases inflammation and intestinal colonisation by Candida albicans in a mouse model of

chemically-induced colitis. Medical Mycology, Vol. 45. Issue 8. pp 691 - 700.

• Kabbani, T. A., et al. (2017). Prospective randomized controlled study on the effects of Saccharomyces boulardii CNCM I-745 and amoxicillin-clavulanate or the

combination on the gut microbiota of healthy volunteers. Gut Microbes, 8(1), 17–32.

• Kurugol Z. & Koturoglu G., (2005), ‘Effects of Saccharomyces boulardii in children with acute diarrhea’. Acta Paediatrica, 94:44-47.

• McFarland L.V., (2010), ‘Systematic review and meta-analysis of Saccharomyces boulardii in adult patients’. World Journal of Gastroenterology, 16(18):2202–

2222

• Matsubara VH., et al (2016) Probiotics as Antifungals in Mucosal Candidiasis. Clin Infect Dis. May Clin Infect Dis. 2016 May 1;62(9):1143-53

• Ménard S et al (2004) Lactic acid bacteria secrete metabolites retaining anti-inflammatory properties after intestinal transport. Gut. 2004 Jun;53(6):821-8

• Micklefield G (2014) Saccharomyces boulardii in the treatment and prevention of antibiotic-associated diarrhea. MMW Fortschr Med. 2014 Apr 17;156 Suppl

1:18-22.

• Murzyn et al., (2010), ‘Capric Acid Secreted by S. boulardii Inhibits C. Albicans’. Plos One, 5(8)

• Murzyn A, et al. (2010) ‘The effect of Saccharomyces boulardii on Candida albicans-infected human intestinal cell lines Caco-2 and Intestin 407’. FEMS

Microbiology Letters 310 (1) 17-23.

• Namkin, K., et al. (2016). Saccharomyces Boulardii in Helicobacter Pylori Eradication in Children: A Randomized Trial From Iran. Iranian Journal of

Pediatrics, 26(1), e3768.

• Plein K, Hotz J. 1993 Therapeutic effects of Saccharomyces boulardii on mild residual symptoms in a stable phase of Crohn's disease with special respect to

chronic diarrhea—a pilot study. Z Gastroenterol; 31: 129-134

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• Tung J.M. et al., (2010), ‘Prevention of Clostridium difficile with Saccharomyces boulardii: A systematic review’. Canadian Journal of

Gastroenterology,23(12):817-821.

• Qamar A., et al. (2001) Saccharomyces boulardii stimulates intestinal immunoglobulin A immune response to Clostridium difficile toxin A in mice. Infect Immun.

69:2672-2765

• Surawicz, C.M. et al. (1989) Treatment of Recurrent Clostridium difficile Colitis with Vancomycin and Saccharomyces boulardii. The American Journal of

Gastroenterology. Vol. 85 (10)

• Surawicz, C.M. et al. (2000) The Search for a Better Treatment for Recurrent Clostridium difficile Disease: Use of High-Dose Vancomycin Combined with

Saccharomyces boulardii. Clinical Infectious Diseases. Vol. 31 pp. 1012 – 1017

• Surawicz, C.M. 2003. Probiotics, antibiotic-associated diarrhoea and Clostridium difficile diarrhoea in humans. Best Practice & Research Clinical

Gastroenterology. Vol. 17 (5) pp. 775 – 783

• Wan CM, et al (2017) A multicenter randomized controlled study of Saccharomyces boulardii in the prevention of antibiotic-associated diarrhea in infants and

young children. 4;55(5):349-354.

• Wu (2007) Saccharomyces boulardii ameliorates Citrobacter rodentium-induced colitis through actions on bacterial virulence factors. Am J Physiol Gastrointest

Liver Physiol; 294, 1: G295-306.

• Zhang DM, et al (2017) A prospective control study of Saccharomyces boulardii in prevention of antibiotic-associated diarrhea in the older inpatients. Jun

1;56(6):398-401.

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Noteworthy Reviews/ Meta-analyses

• McFarland 2010: Systematic review and meta-analysis of Saccharomyces boulardii in

adult patients

– 27 RCT / 5029 patients

– Prevention of AAD, TD, CDD recurrences

• Doron 2008: Probiotics for prevention of antibiotic-associated diarrhoea

– 5 meta-analysis performed on AAD and probiotics

– overall reduction in the risk of AAD when probiotics co-administered with antibiotics

• McFarland 2007: Meta-analysis of probiotics for prevention of traveler's diarrhoea

– probiotics including S. boulardii had significant efficacy in prevention of TD

• McFarland 2006: Meta-analysis of probiotics for the prevention of AAD and the

treatment of C. difficile Disease– Probiotics significantly reduced the relative risk of AAD

• Szajewska 2005: Meta-analysis: non-pathogenic yeast Saccharomyces boulardii in the

prevention of antibiotic-associated diarrhoea– 5 RCT were included / 1076 participants

– Boulardii reduced significantly the risk of diarrhea from 17.2% to 6.7%, No side effects were

reported