Systematic review and meta-analysis of Saccharomyces boulardii in adult patients

Table 1 Examples of commercially available probiotics containing “Saccharomyces boulardii”

Product name	Probiotic strain	Manufacturer	Stable at room temp1	Facility certified	Strain confirmed	Colony forming unit (cfu) per mg capsule or mL	Original strain-specific studies	Degree of clinical evidence2
Single strain
Florastor® (US) Perenterol® (Germany) Reflor® (Turkey) Ultra-Levure® (Asia)3	S. boulardii lyo	Biocodex (France)	Yes	EU GMP	Microsatellite sequency poly-morphism [28,29]	5 × 109/250 mg	Multiple[37-62]	A
SB+MOS	S. boulardii	Jarrow Formulas (Los Angeles, CA) and Gnosis (Italy)	No	EU GMP	Not stated	1.5 × 109	One study[63]	C
Saccharomyces boulardii	S. boulardii	Kirkman (Oregon)	No	GMP	DNA finger-print	3 × 109/150 mg	None	F
Saccharomyces boulardii	S. boulardii	Allergy Research Group (CA)/NutriCology (CA)	No	GMP	DNA finger-print	3 × 109/150 mg	None	F
Saccharomyces boulardii	S. boulardii	Klaire Labs (Reno Nevada)	No	GMP ISO 9001	Ribotyping	3 × 109/150 mg	None	F
In mixtures of probiotics
Protecflor® (Canada) Erce Flora® (Belgium)	S. cerevisiae boulardii CNCM I-1077) + L. rhamnosus + L. acidophilus + Bifido. strain	Institut Rosell-Lallemand (Quebec, Canada)	Not stated	Canadian GMP	Not stated	109/2 mL	Two studies [64,65]	D
MitoMix®	S. boulardii and Pediococcus acidilactici	Imagilin Technology (Maryland)	Yes	Not stated	Not stated	2.3 × 109/capsule	One study[66]	D
Primal Defense™	S. boulardii with 13 other strains4	Garden of Life (FL)	Yes	Not stated	No (only certified “organic”)	Total 1 × 109 per 410 mg	None	F
Pro-Bio Defense™	S. boulardii + 7 other strains5	Kirkman (OR)	No	GMP	DNA finger-print	Total: 2 × 1010/cap, no data on SB cfu	None	F
ABX Support™	S. boulardii + L. rhamnosus + Bifido. bifidum + Bifido. breve	Klaire Labs (NEV)	No	GMP ISO 9001	Ribotyping	5 × 109/300 mg	None	F
Kombucha fermented tea	S. boulardii + L. bacterium + blue-green algae	Millennium Products, Inc.	No	No	Not stated	1 × 109 per 16 oz.	None	F

¹Products not stable at room temperature require refrigeration, probably heat-dried. Products stable at room temperature are typically packaged in blister packs and are lyophilized;

²Degree of evidence: A = at least two randomized, controlled clinical trials in patients; B = one randomized controlled clinical trial in patients, C = case reports, uncontrolled randomized trials or open safety/kinetic studies in patients or volunteers, D = in vivo animal model or in vitro studies only, E = expert opinion only, F = no direct evidence;

³A few examples, Biocodex has over 40 brand names worldwide;

⁴Other strains in Primal Defense include: 11 strains of Lactobacilli (L. acidophilus, L. bulgaricus, L. lactis, L. plantarum, L. casei, L. lactis, L. leichmannii, L. brevis, L. caucasicus, L. fermenti, L. helveticus and 1 strain each: Bifidobacterium bifidum, Bacillus subtilis, Bacillus lichenformis);

⁵Other strains in Pro-Bio Defense include: 5 strains of Lactobacilli (L. plantarum, L. rhamnosus, L. acidophilus, L. casei, L. bulgaricus) and Bifidobacterium lactis and Streptococcus thermophilus. GMP: Good manufacturing practices.

Table 2 Randomized, controlled trials for the prevention of antibiotic associated diarrhea (AAD) using S. boulardii

Ref.	Treatment groups	Population	Daily dose: cfu/d (mg/d)	Duration (d)	Follow-up (wk)	AAD in S. boularii (%)	AAD in controls (%)
Adam et al[37]	S. boulardii vs placebo	388 hospitalized adults, multisite	4 × 109 (200 mg)	7	0	9/199 (4.5)a	33/189 (17.5)
Monteiro et al[55]	S. boulardii vs placebo	240 adults, Portugal	(nr) 4 caps/d	6	0	19/121 (15.7)a	33/119 (27.7)
Surawicz et al[58]	S. boulardii vs placebo	180 hospitalized adults at one hospital, Washington	2 × 1010 (1000 mg)	abx + 14 d	2-3	11/116 (9.5)a	14/64 (21.8)
McFarland et al[54]	S. boulardii vs placebo	193 hospitalized adults (1 or more beta-lactam antibiotics), 4 hospitals	2 × 1010 (1000 mg)	abx + 3 d	7	7/97 (7.2)a	14/96 (14.6)
Lewis et al[133]	S. boulardii vs placebo	72 enrolled, 69 done; elderly patients	4.5 × 109 (226 mg)	14	0	7/33 (21)	5/36 (13.9)
Cremonini et al[134]	S. boulardii vs placebo	43 H. pylori + adults on triple therapy	5 × 109 (nr)	14	2	1/22 (5)a	6/21 (30)
Duman et al[44]	S. boulardii vs placebo	389 adults in Turkey with H. pylori + peptic ulcers, all received triple therapy	2 × 1010 (1000 mg)	14	4	14/204 (6.9)a	28/180 (15.6)
Can et al[135]	S. boulardii vs placebo	151 adult inpatients	1 × 1010 (500 mg)	abx	4	1/73 (1.4)a	7/78 (9.0)
Cindoruk et al[42]	S. boulardiivs placebo	124 adults with H. pylori + dyspepsia	2 × 1010 (1000 mg)	14	6	9/62 (14.5)a	19/62 (30.6)
Bravo et al[136]	S. boulardiivs placebo	89 adult outpatients on amoxicillin	1 × 1010 (500 mg)	12	9	3/41 (7.3)	5/45 (11.1)

^aP < 0.05, probiotic vs controls. cfu: Colony forming unit; nr: Not reported; abx: Antibiotics.

Table 3 Randomized controlled trials for the treatment of C. difficile disease using S. boulardii

Ref.	Treatment groups	Study population	Daily dose: cfu/d (mg/d)	Duration of treatment (wk)	Follow-up(wk)	C. difficile recurrence in probiotic group	C. difficile recurrence in placebo group
McFarland et al[53]	S. boulardii vs placebo	124 adult patients on varied doses of vancomycin or metronidazole; recurrent and initial CDAD cases; 3 referral sites, US	3 × 1010 (1000 mg)	4	4	15/57 (26.3%)a	30/67 (44.8%)
Surawicz et al[60]	S. boulardii vs placebo	168 adult patients recurrent CDAD; on vancomycin (2 g/d, n = 32) or V (500 mg/d, n = 83) or M (1 g/d, n = 53); 4 referral sites, US	2 × 1010 (1000 mg)	4	4	V (2 g/d) 3/18 (17%)a; V (500 mg/d) 23/45 (51%); M (1 g/d) 13/27 (48.1%)	V (2 g/d) 7/14 (50%); V (500 mg/d) 17/38 (44.7%); M (1 g/d) 13/26 (50%)

^aP < 0.05, probiotic vs controls. V: Vancomycin; M: Metronidazole.

Table 4 Randomized, controlled trials for acute disease conditions using S. boulardii

Ref.	Treatment groups	Study population	Daily dose: cfu/d (mg/d)	Duration of treatment	Follow-up(wk)	Outcome in probiotic	Outcome in controls
	Helicobacter pylori
Cremonini et al[134]	S. boulardii (Codex, SmithKine Beecham, Italy) vs placebo vs LGG vs mix (L acid and Bifid lactis)	85 asymptomatic carriers H. pylori 22 SB and 21 placebo; all received triple therapy	5 × 109 (nr)	2 wk	2	Eradicated in: 17/21 (81%) same for LGG and mix	Placebo, 16/20 (80%)
						Any symptoms: 4/21 (19%)a	Any symptoms: 12/20 (60%)
Cindoruk et al[42]	S. boulardii (Reflor, Turkey) vs placebo	124 adults with H. pylori dyspepsia, all received triple therapy	2 × 1010 (1000 mg)	2 wk	6	Eradication 44/62 (71%)	Eradication 37/62 (59.7%)
						Epigastric distress: 9 (14.5%)a	Distress: 27 (43.5%)
	Acute adult diarrheas
Hochter et al[169]	S. boulardii vs placebo	92 German outpatient adults	8 × 109 (300-600 mg)	8 d	0	Diarrhea score reduction: -17.2 + 6.8a	Score: -13.6 + 8.7
Mansour- ghanaei et al[51]	S. boulardii (UltraLevure, France) vs placebo. Both groups got metro and lodoquinol	57 enrolled, 54 done; adults with E. histolytica amoebic dysentery	1.5 × 1010 (750 mg)	10 d	4	Cured: 27/27 (100%)a	Cured: 5/27 (19%)
	Enteral feeding-related diarrhea
Tempe et al[61]	S. boulardii vs placebo	40 adults in ICU	1 × 1010 (nr)	11-21 d	0	34/389 days of diarrhea (8.7%)a	63/373 days of diarrhea (16.9%)
Schlotterer et al[171]	S. boulardiivs placebo	20 enrolled, 18 done, burnt adults 18-70 yr	4 × 1010 (2000 mg)	8-28 d	0	3/204 days of diarrhea (1.5%)a	19/208 days of diarrhea (9.1%)
Bleichner et al[39]	S. boulardii vs placebo	131 enrolled, 128 done, adults in ICU	4 × 1010 (2000 mg)	3 wk	0	50/648 days of diarrhea (7.7%)a	87/683 days of diarrhea (12.7%)
	Traveler’s diarrhea
Kollaritsch et al[175]	S. boulardii vs placebo	832 Austrian tourists to hot climates	2 × 109 (250 mg)	5 d before trip and mean 21 d trip	0	143/426 (34%)a	173/406 (43%)
Kollaritsch et al[175]	S. boulardii vs placebo	805 Austrian tourists to hot climates	5 × 109 (500 mg)	5 d before trip and mean 21 d trip	0	127/399 (32%)a	173/406 (43%)
Kollaritsch et al[49]	S. boulardii vs placebo	713 Austrian tourists to hot climates	2 × 109 (250 mg)	5 d before trip and mean 21 d trip	0	121/352 (34%)a	141/361 (39%)
Kollaritsch et al[49]	S. boulardii vs placebo	664 Austrian tourists to hot climates	2 × 1010 (1000 mg)	5 d before trip and mean 21 d trip	0	87/303 (29%)a	141/361 (39%)
Bruns et al[176]	S. cerevisiae Hansen (CBS 5926) vs active treatment1	60 tourists in Tunisia with traveler’s diarrhea, 43 done	1.0 × 1010 (600 mg)	5 d	0	Duration diarrhea 2.1 d	1.4 days of diarrheaa

^aP < 0.05, probiotic vs controls;

¹Strain currently known as S. boulardii.

Table 5 Randomized, controlled trials for chronic disease conditions using S. boulardii

Ref.	Treatment groups	Study population	Daily dose: cfu/d (mg/d)	Duration of treatment and follow-up	Outcome in probiotic	Outcome in controls
	Crohn’s disease
Plein et al[57]	S. boulardii (Perenterol®) vs placebo	20 enrolled with Crohn’s, 17 done, all on maintenance medications	1.5 × 1010 (750 mg)	7 wk	3.3 ± 1.2 stools/d at week 9a	4.6 ± 1.9 stools/d at week 9
Guslandi et al[47]	S. boulardii (Perenterol®) + mesalamine (2 g/d) vs mesalamine alone (3 g/d)	32 with Crohn’s in remission in Italy (23-49 yr old)	2 × 1010 (1000 mg)	6 mo	1/16 (6%) relapsea	6/16 (38%) relapse
	Irritable bowel syndrome
Maupas et al[52]	S. boulardii vs placebo	34 with IBS	9 × 109 (nr)	4 wk	Mean decrease in #stools/d: -2.2/da	Mean decrease -0.5/d
					Improved: 14/16 (87.5%)a	Improved: 13/18 (72%)
	Giardiasis
Besirbellioglu et al[38]	S. boulardii + metro (2250 mg/d) vs placebo + metro	65 adults with giardiasis	1 × 1010 (500 mg)	10 d with 4 wk f/up	100% cured, 0% giardia cystsa	100% cured 6/35 (17%) cysts present
	HIV-related diarrhea
Saint- Marc et al[189]	S. boulardii vs placebo	35 French AIDS patients with chronic diarrhea	6 × 1010 (3000 mg)	7 d	11/18 (61%) cureda	2/17 (12%)

^aP < 0.05, probiotic vs controls. IBS: Irritable bowel syndrome; HIV: Human immunodeficiency virus; AIDS: Acquired immune deficiency syndrome; f/up: Follow-up time.

Table 6 Summary of recommendations for clinical use of S. boulardii in adults

Use for disease	Dose (mg/d)	Duration	Adjunct to	Strength of evidence1
Prevention of antibiotic associated diarrhea	500-1000	During antibiotics with additional 3 d to 2 wk after	Nothing	++++
Prevention of Traveler’s diarrhea	250-1000	Duration of trip (3 wk)	Nothing	+++
Enteral nutrition-related diarrhea	2000	8-28 d	Nothing	++
H. pylori symptoms	1000	2 wk	Standard triple therapy	++
Treatment of Clostridium difficile infections	1000	4 wk	Vancomycin or metronidazole	+
Acute adult diarrhea	500-750	8-10 d	Nothing	+
Inflammatory bowel disease	750-1000	7 wk to 6 mo	Mesalamine	+
Irritable bowel syndrome	500	4 wk	Nothing	+
Giardiasis	500	4 wk	Metronidazole	+
HIV-related diarrhea	3000	7 d	Nothing	+

¹Strength of evidence, + (weak, needs more randomized controlled trials) to ++++ (strong, efficacy and safety are evidence based from numerous large randomized controlled trials).