ORIGINAL ARTICLE

A Randomized, Double-blind, Placebo-controlled

Multicenter Trial of Saccharomyces boulardii
in Irritable Bowel Syndrome
Effect on Quality of Life
Chang Hwan Choi, MD, PhD,* Sun Young Jo, MD,* Hyo Jin Park, MD, PhD,w
Sae Kyung Chang, MD, PhD,* Jeong-Sik Byeon, MD, PhD,z and Seung-Jae Myung, MD, PhDz

typical symptoms are abdominal pain, constipation, diar-

Background: Probiotics confer health benefits to the host. However, rhea, and bloating.1–3 IBS is not lethal; however, can reduce
its clinical effect on irritable bowel syndrome (IBS) is controversial. quality of life (QOL) and increase medical costs. Several
Aims: This study was aimed to evaluate the effects of Sacchar- mechanisms for symptoms have been proposed, including a
omyces boulardii on quality of life (QOL) and symptoms in patients disturbed intestinal motility, visceral hypersensitivity,
with diarrhea-predominant IBS or mixed-type IBS. abnormal brain-gut interaction, and autonomic nervous
system abnormalities.4–8 IBS might be caused by changes in
Methods: Sixty-seven patients with IBS were randomized either to
intestinal flora, intestinal infection, and activation of the
receive S. boulardii at 2 1011 live cells as a daily dose (n=34), or
placebo (n=33) for 4 weeks. IBS-QOL was assessed at the mucosal immune system.9–13
beginning and end of the treatment phase. IBS-related symptoms, Probiotics are nonpathogenic microorganisms that give
bowel movement frequency, and stool consistency were recorded health benefits to the host.14 Lactobacilli, bifidobacteria, and
on a daily basis and assessed each week. nonpathogenic yeasts, such as Saccharomyces boulardii, are
the most common probiotics and may influence gastrointest-
Results: The overall improvement in IBS-QOL was higher in S.
inal disorders including acute infectious diarrhea, inflamma-
boulardii group than placebo (15.4% vs 7.0%; P<0.05). All eight
domains of IBS-QOL were significantly improved in S. boulardii tory bowel diseases, allergic disorders, and IBS.15 Probiotics
group; however, placebo group only showed improvements in competitively inhibit pathologic bacteria and abnormal
dysphoria and health worry. Composite scores for IBS symptoms fermentation, synthesize antibacterial substances, prevent
were significantly reduced in both groups to a similar extent. Bowel bacterial translocation, enhance gut barrier function, and
frequency and stool consistency did not change in either group. modulate signaling pathways in the mucosal immune
system.16–21 However, few randomized controlled trials have
Conclusions: S. boulardii improved IBS-QOL better than placebo
but was not superior for individual symptoms in patients with tested the efficacy of probiotics for IBS and the results were
diarrhea-predominant IBS or mixed-type IBS. controversial.22 The aims of this study were to evaluate
the effects of S. boulardii on QOL and symptoms in patients
Key Words: irritable bowel syndrome, probiotics, quality of life with IBS.
(J Clin Gastroenterol 2011;45:679–683)
MATERIALS AND METHODS
Patients
Irritable bowel syndrome (IBS) is a common disorder
characterized by persistent or recurrent abdominal pain
and discomfort with altered bowel habits. It affects
We recruited patients with IBS at Chung-Ang
University Hospital, Gangnam Severance Hospital, and
approximately 10% to 20% of the adult population, and Asan Medical Center from September, 2006, until April,
2007. Diagnosis of IBS was based on Rome II criteria; at
least 12 weeks (which do not need to be consecutive) in the
Received for publication July 5, 2010; accepted October 28, 2010. preceding 12 months of abdominal discomfort or pain that
From the *Department of Internal Medicine, Chung-Ang University has 2 of 3 features: relieved by defecation and/or associated
College of Medicine; wDepartment of Internal Medicine, Yonsei changes in stool frequency and/or stool consistency. The
University College of Medicine; and zDepartment of Internal
Medicine, University of Ulsan College of Medicine, Seoul, Republic
study was carried out in patients with diarrhea-predomi-
of Korea. nant type IBS (IBS-D) or mixed-type IBS (IBS-M) but
Supported in part by a research fund from Kuhnil Co. Korea. excluding constipation-predominant IBS.3 The inclusion
Chang Hwan Choi and Sun Young Jo have contributed equally to this criteria were: men or women aged between 20 and 65 years;
study.
Presented at the United European Gastroenterology Week 2007 as a
organic abnormality excluded by blood chemistry and
poster presentation. colonoscopy performed during the screening period; and
Conflict of Interest Disclosure: None. signed written informed consent. Women of reproductive
Reprints: Seung-Jae Myung, MD, PhD, Department of Internal age were verified as not pregnant and used contraception
Medicine, University of Ulsan College of Medicine, Asan Medical
Center, 388-1 Pungnap-dong, Songpa-gu, Seoul, 138-736 Korea
during the study. Exclusion criteria included intolerance to
(e-mail: [email protected]). yeasts or lactose; pregnancy or lactation; severe systemic
Copyright r 2011 by Lippincott Williams & Wilkins illness (liver cirrhosis, congestive heart failure, chronic renal

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Choi et al J Clin Gastroenterol  Volume 45, Number 8, September 2011

failure, angina, uncontrolled hypertension, endocrine dis- performed at least once through follow-up in both groups
order, metabolic disorder, malignant tumors); concurrent of patients.
psychiatric disorder; previous abdominal surgery other
than appendectomy and abdominal wall hernia repair;
Statistical Analyses
history of other clinical trial within 3 months before onset
of this trial; use of drugs influencing the evaluation of SPSS Window version 13.0 was used to perform all
efficacy during study period; and the patients judged data analyses. Categorical variables were compared with
ineligible by a clinician. The study protocol was approved the w2 test, and continuous variables were compared with
by the ethics review committee of each hospital. Student t test for clinical characteristics. We used the paired
t test to compare primary and secondary efficacies within
groups, and Student t test to compare the percentage of
Randomization of Treatment Group or Placebo change before and after administration between the 2
Group and Administration of Drug groups. Differences in the incidence of adverse events were
This study used randomized allocation. Patients who analyzed using Fisher exact test in safety assessment. The
met inclusion criteria and consented to participation were data are expressed as mean±SD, and statistical signifi-
randomly allocated to treatment or placebo groups cance was determined at P<0.05.
according to a blocked randomization allocation sequence.
Patients received Bioflor (Kuhnil, Seoul, Republic of
Korea; S. boulardii at 2  1011 live cells) or matching RESULTS
placebo, 2 capsules twice daily, orally for 4 weeks. The
investigators and the patients were blinded to the assign- Baseline Characteristics
ment. Compliance was calculated as percentage of planned Ninety-four patients entered the screening phase of the
ingestion of the study product, and a compliance rate above study (mean age 41 y; 48 female patients) (Fig. 1). Of these,
80% was set as minimum. 90 patients (mean age 41±13 y; 46 female) were random-
ized and entered the treatment phase. Four patients
withdrew their informed consent before the treatment
Progress of Clinical Trials phase because of factors unrelated to the study. Forty-five
Patients who fulfilled the inclusion criteria by means of patients were randomized to receive the active treatment
a clinical history, physical examination, drug use, colono- and 45 to the placebo group. There was no significant
scopy, and blood tests were evaluated by IBS-QOL and difference in sex, height, weight, smoker, alcohol intake,
recorded symptoms, bowel movement frequency, and stool duration of IBS, and subtypes between the 2 groups
consistency on a daily basis for 1 week before study (Table 1). Of these, 23 patients who were lost to follow-
initiation. The symptoms, adverse effects, bowel movement up, had adverse effects, took antidepressants, or had
frequency, and stool consistency were recorded daily during inadequately recorded symptom scores were excluded from
the study period, and QOL was assessed after 4 weeks. efficacy analyses. Thirty-four patients completed the study
Patients visited the study unit to receive the investigational in the treatment group and 33 patients in the placebo
products and to assess compliance, symptoms, and safety at group.
every 2 weeks after first administration. After the treatment
period, in cases of abnormal laboratory tests, patients made
another visit within 2 weeks to assess adverse effects and for
Effect of S. boulardii on IBS-QOL
final safety evaluation. The percentage of changes in IBS-QOL scores before
and after treatments were compared between the 2
treatment groups. Overall IBS-QOL improved in both
Efficacy Measures groups compared with baseline; however, the S. boulardii
The primary efficacy variable was the difference in group showed a significantly better improvement than the
QOL after 4-week treatment using the IBS-QOL ques- placebo group (15.4% vs 7.0%; P<0.05; Table 2). All 8
tionnaire, evaluated as the percentage of change in scores. domains (dysphoria, interference with activity, body image,
QOL assessment was performed using the Korean version health worry, food avoidance, social reaction, sexual, and
of Irritable Bowel Syndrome Quality of Life developed by relationships) of IBS-QOL were significantly improved in
Patrick et al.23,24 The instrument contains 34 items scored
from 1 to 5 to derive 8 subscale scores (dysphoria,
interference with activity, body image, health worry, food 94 screened
avoidance, social reaction, sexual, and relationships)
transformed to a scale of 0 to 100, with 100 representing 4 screening failures
the best possible QOL. We also evaluated changes in 10
symptoms related to IBS (abdominal pain, discomfort,
90 randomized
hard/lumpy stool, loose/watery stool, straining, urgency,
sense of incomplete evacuation, mucus in stool, bloating,
passage of gas) for 5 weeks (1 wk baseline and 4 wk 45 active treatments 45 placebos
treatment) as secondary efficacy variables. Patients re-
corded daily symptoms using the 7-point Likert scale 11 drop-outs 12 drop-outs
(ranging from 0 to 6), and the changes of weekly mean
scores were measured. We also assessed the frequency
(number per day) and the consistency of stools using the
34 completed the study 33 completed the study
Bristol stool Scale, which ranges from 1 to 7 and a high
score indicates looser stool. Safety assessments were FIGURE 1. Schematic diagram of the study flow.

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J Clin Gastroenterol  Volume 45, Number 8, September 2011 Effect of S. boulardii in IBS

treatment, respectively, and 4.8±1.2 and 4.2±1.2 before

TABLE 1. Baseline Characteristics of Each Group and after placebo, respectively.
S. boulardii Placebo
Characteristics (N=45) (N=45) P Adverse Events
Age (y) 40.2±13.1 40.6±12.9 0.90 No adverse events were reported in S. boulardii group
Sex (%) 0.82 (n=39), but 1 patient in the placebo group (n=43)
Male 18 (51.4) 19 (48.7) withdrew due to worsening abdominal pain and flatulence.
Female 17 (41.6) 20 (51.3)
Height (cm) 167.0±8.8 164.8±8.3 0.21
Body weight (kg) 64.9±11.0 62.3±14.2 0.40 DISCUSSION
Smoker 7 (20.0) 8 (20.5) 0.96 IBS results from a multi-factorial pathophysiology
Alcohol intake 18 (51.4) 17 (43.6) 0.50 that involves intestinal infection, immune activation,
Duration of IBS 81.1±67.3 74.9±95.9 0.90 abnormal gastrointestinal motility, abnormal colonic fer-
(months) mentation, visceral hypersensitivity, increased intestinal
Subtypes of IBS (%) 0.97 permeability, autonomic nerve abnormality, psychosocial
IBS-D 25 (71.4) 28 (71.8)
factors, specific gene abnormality, and intestinal bacterial
IBS-M 10 (28.6) 11 (28.2)
overgrowth.1,7,10,12,25–27 Current treatment of IBS, such as
Data are shown as mean±SD and numbers with percentages in fiber, antidepressants, serotonin antagonists, and antispas-
parentheses. modics, focus on alleviating symptoms but are often
IBS indicates irritable bowel syndrome; IBS-D, diarrhea-predominant unsatisfactory.1 Probiotics can modulate the intraluminal
IBS; IBS-M, Mixed-type IBS.
milieu and inhibit inflammation to potentially treat IBS.
However, the effects of probiotics in patients with IBS are
still controversial, and a limited number of randomized
controlled trials have been performed to validate the
the S. boulardii group, but only dysphoria and health worry efficacy of probiotics for IBS.22
improved in the placebo group (P<0.05; Table 2). We, therefore, evaluated the effects of S. boulardii on
QOL and symptoms in patients with IBS-D or IBS-M.
Effect of S. boulardii on Symptoms Probiotic treatment improved overall QOL more than
and Bowel Movement placebo. Not all IBS symptoms can originate in the
Both groups showed improvement in the mean values bowel,28 including psychological problems that affect
of 10 symptoms over the treatment period (24.6% in relationships and social interactions, making QOL an
S. boulardii and 20.4% in placebo; P<0.01; Table 3). Of important measure in patients with IBS29,30 that determines
these 10 symptoms, abdominal discomfort, mucus in stool, when to initiate treatment.31 Mental QOL includes
and passage of gas were significantly improved in the sexuality, mood, and anxiety.32 We used the Korean IBS-
S. boulardii group, whereas the placebo group showed QOL questionnaire, a translation of the IBS-QOL ques-
improvement in loose/watery stool, sense of incomplete tionnaire developed by Patrick et al23 in Korean,24 that
evacuation, and passage of gas (P<0.05; Table 3). contains 34 questions in 8 domains and has high reliability
However, the percentage of changes in total mean scores and internal validity. Body image and food avoidance are
and subscores were similar in the 2 groups (Table 3). Daily physical QOL components, whereas dysphoria, interference
bowel movements were similar in the 2 groups and not with activity, health worry, social reaction, sexuality, and
changed significantly after treatment. Those were 1.8±1.4 relationships are mental QOL components. Probiotic
and 1.6±0.8 before and after S. boulardii treatment, treatment improved all QOL domains, whereas placebo
respectively, and 1.9±1.2 and 1.4±0.7 before and after only improved dysphoria and health worry.
placebo, respectively. Similarly, Bristol stool scale values The effects of both treatments were not different on
were 4.9±1.0 and 4.9±1.2 before and after S. boulardii secondary variables of individual symptoms and bowel

TABLE 2. IBS-QOL Mean Scores and Percentage of Changes Calculated by Scores Before and After 4 wk of Treatment
QOL Mean Scores±SD and Change Rates (%)
Baseline After 4 wk Change Rates (%)
Domains of IBS-QOL S. boulardii Placebo S. boulardii Placebo S. boulardii Placebo P
Dysphoria 68.0±14.4 70.1±23.2 79.3±13.7 78.0±18.7 19.5±23.1 20.7±36.8 0.87
Interference with activity 67.4±18.9 74.2±19.6 77.8±17.8 76.0±20.7 19.1±23.2 4.2±16.0 <0.01
Body image 78.0±17.6 77.1±17.0 84.5±16.4 79.9±17.3 10.3±22.3 6.4±22.1 0.50
Health worry 65.6±12.2 77.0±15.3 79.4±8.6 83.0±9.7 24.8±26.2 12.1±27.3 0.07
Food avoidance 60.9±22.6 58.6±19.1 69.5±22.2 65.8±19.4 24.2±46.4 23.1±66.7 0.94
Social reaction 74.1±17.5 81.1±16.9 83.8±15.1 82.6±17.3 18.8±33.7 3.0±15.2 0.02
Sexual 86.6±21.0 85.0±20.9 92.9±17.8 86.9±18.9 10.9±27.8 5.3±21.8 0.39
Relationships 79.2±13.7 80.0±16.8 86.8±13.3 83.6±17.8 11.4±19.7 6.7±24.6 0.42
Overall 70.9±12.8 74.8±15.7 80.8±12.3 79.0±15.3 15.4±16.4 7.0±13.5 0.03
Change rate (%)=(Week 4 score  Week 0 score)/Week 0 score  100.
Data are shown as mean±SD.
IBS indicates irritable bowel syndrome; QOL, quality of life.

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Choi et al J Clin Gastroenterol  Volume 45, Number 8, September 2011

TABLE 3. Percentage of Changes of Likert Scores Calculated by Scores Before and After 4 wk of Treatment
Likert Mean Scores±SD and Change Rates (%)
Baseline After 4 wk Change Rates (%)
Symptoms S. boulardii Placebo S. boulardii Placebo S. boulardii Placebo P
Abdominal pain 1.6±0.9 1.5±1.2 1.3±1.1 1.2±0.9 13.9±72.1 27.8±127.9 0.13
Abdominal discomfort 2.2±1.2 2.1±1.2 1.3±1.2 1.5±1.1 37.2±46.1 16.6±73.6 0.19
Hard/lumpy stool 0.8±0.6 1.2±0.8 0.9±1.1 1.1±1.1 29.9±207.9 14.6±130.9 0.77
Loose/watery stool 2.4±1.6 2.7±1.4 1.9±1.6 1.4±1.2 36.0±98.7 32.6±68.1 0.15
Straining 1.6±1.1 2.0±1.3 1.1±1.0 1.5±1.3 57.3±317.7 9.3±80.2 0.28
Urgency 2.4±1.6 2.1±1.5 1.6±1.3 1.3±1.4 20.9±78.8 26.8±72.1 0.77
Sense of incomplete evacuation 2.3±1.5 2.5±1.6 1.4±1.1 1.6±1.3  5.6±159.4 34.4±50.9 0.19
Mucus in stool 0.9±0.9 1.2±1.0 0.3±0.4 0.6±0.9 64.5±53.0 67.2±46.9 0.89
Bloating 2.7±1.4 3.0±1.6 1.7±1.3 2.2±1.4 21.1±76.6 13.8±77.2 0.72
Passage of gas 2.7±1.5 2.9±1.5 1.7±1.4 2.1±1.4 27.6±53.7 22.2±54.9 0.69
Total 1.7±0.8 1.8±0.9 1.2±0.8 1.3±0.8 24.6±39.2 20.4±37.4 0.66
Change rate (%)=(Week 4 score  Week 0 score)/Week 0 score  100.
Data are shown as mean±SD.

habits. S. boulardii may have a greater effect on the small administration of S. boulardii in rats stimulated intestinal
intestine than the colon, and therefore, be unable to secretion of IgA and expression of polymeric immunoglobu-
improve colon-related symptoms. Alternatively, S. boulardii lin receptor in intestinal glandular cells.50 (3) Secretory effect
might improve overall QOL through systemic effects, such on intestinal mucus; S. boulardii increased secretion and
as inhibition of proinflammatory cytokines, which probably activity of the brush border enzyme.51 Further studies are
modulate the activity of the nervous system, or increases in needed to elucidate the mechanism of action in patients with
tryptophan, rather than local effects, such as inhibition of IBS.
mucosal inflammation, abnormal fermentation, or aug- Our short trial may have limited the ability to detect
mentation of mucosal barrier function.33–35 Patients with changes in individual symptoms, and we did not measure S.
fructose malabsorption show unusual bacterial profiles boulardii levels in the colon with microbial culture or DNA
because of abnormal fermentation, leading to lower plasma analysis. Finally, we only used 1 dose of S. boulardii,
tryptophan levels and subsequent depression.36–39Bifido- therefore, do not know the optimal dosing paradigm.
bacteria infantis attenuates the production of proinflamma- In conclusion, S. boulardii (Bioflor, Kuhnil) improved
tory cytokines and increased plasma levels of tryptophan IBS-QOL, the primary endpoint, better than placebo in
in animals.33 Probiotics also inhibit the release of adreno- patients with IBS-D or IBS-M. Although it may be difficult
corticotropic hormone and corticosterone,40 and provoke to expect S. boulardii to improve specific symptoms
behavioral alterations by releasing soluble factors.41,42 prominently, overall satisfaction and QOL can be im-
Finally, dosing could have been sufficient to improve proved. Future studies to determine optimal dose, treat-
patient QOL, but inadequate to improve individual ment duration, and mechanism of action of S. boulardii are
symptoms. needed.
B. infantis significantly alleviated abdominal pain/dis-
comfort, bloating/distension, and bowel movement diffi- REFERENCES
culty compared with placebo.34 In another study of 86 1. Drossman DA, Camilleri M, Mayer EA, et al. AGA technical
patients with IBS, probiotics improved the severity of IBS review on irritable bowel syndrome. Gastroenterology. 2002;
symptoms and QOL.43 However, a fermented milk contain- 123:2108–2131.
ing 3 probiotic bacteria was not effective on QOL and on 2. Lee OY. Prevalence and risk factors of irritable bowel
symptoms in patients with IBS.44 Our results may differ syndrome in Asia. J Neurogastroenterol Motil. 2010;16:47–51.
from these studies due to differences in probiotic strains or 3. Thompson WG, Longstreth GF, Drossman DA, et al.
doses, racial differences, or different food habits of the Functional bowel disorders and functional abdominal pain.
study populations. Gut. 1999;45(suppl 2):II43–II47.
4. Abrahamsson H. Gastrointestinal motility in patients with the
S. boulardii yeast has various advantages: it survives
irritable bowel syndrome. Scand J Gastroenterol (Suppl 1).
passage through the gastrointestinal tract, its temperature 1987;130:21–26.
optimum is 371C in vitro and in vivo, it inhibits the growth of 5. Bouin M, Plourde V, Boivin M, et al. Rectal distention testing
microbial pathogens, and it has no severe adverse effects.45 in patients with irritable bowel syndrome: sensitivity, specifi-
The clinical effect of S. boulardii has been proven in city, and predictive values of pain sensory thresholds.
antibiotic-associated diarrhea, Clostridium difficile infection, Gastroenterology. 2002;122:1771–1777.
traveller’s diarrhea, acute diarrhea in children, tube-feeding- 6. Whitehead WE, Palsson OS. Is rectal pain sensitivity a
associated diarrhea, AIDS-related diarrhea, and inflamma- biological marker for irritable bowel syndrome: psychological
tory bowel diseases.45–47 This probiotics work by: (1) anti- influences on pain perception. Gastroenterology. 1998;115:
1263–1271.
inflammatory effect; S. boulardii produced factors to
7. Silverman DH, Munakata JA, Ennes H, et al. Regional
neutralize bacterial toxins,48 and inhibited the infiltration of cerebral activity in normal and pathological perception of
T helper type 1 cells in the inflamed colon and the production visceral pain. Gastroenterology. 1997;112:64–72.
of proinflammatory cytokines in IBS animal models.49 (2) 8. Aggarwal A, Cutts TF, Abell TL, et al. Predominant
Immunoprotective effect in the gastrointestinal tract; oral symptoms in irritable bowel syndrome correlate with specific

682 | www.jcge.com r 2011 Lippincott Williams & Wilkins

J Clin Gastroenterol  Volume 45, Number 8, September 2011 Effect of S. boulardii in IBS

autonomic nervous system abnormalities. Gastroenterology. 32. Spiegel BM, Gralnek IM, Bolus R, et al. Clinical determinants
1994;106:945–950. of health-related quality of life in patients with irritable bowel
9. Balsari A, Ceccarelli A, Dubini F, et al. The fecal microbial syndrome. Arch Intern Med. 2004;164:1773–1780.
population in the irritable bowel syndrome. Microbiologica. 33. Desbonnet L, Garrett L, Clarke G, et al. The probiotic
1982;5:185–194. Bifidobacteria infantis: an assessment of potential antidepres-
10. Chadwick VS, Chen W, Shu D, et al. Activation of the mucosal sant properties in the rat. J Psychiatr Res. 2008;43:164–174.
immune system in irritable bowel syndrome. Gastroenterology. 34. O’Mahony L, McCarthy J, Kelly P, et al. Lactobacillus and
2002;122:1778–1783. bifidobacterium in irritable bowel syndrome: symptom re-
11. Isolauri E, Kirjavainen PV, Salminen S. Probiotics: a role in sponses and relationship to cytokine profiles. Gastroenterology.
the treatment of intestinal infection and inflammation? Gut. 2005;128:541–551.
2002;50(suppl 3):III54–III59. 35. Pessi T, Sutas Y, Hurme M, et al. Interleukin-10 generation in
12. Rodriguez LA, Ruigomez A. Increased risk of irritable bowel atopic children following oral Lactobacillus rhamnosus GG.
syndrome after bacterial gastroenteritis: cohort study. BMJ. Clin Exp Allergy. 2000;30:1804–1808.
1999;318:565–566. 36. Ledochowski M, Widner B, Sperner-Unterweger B, et al.
13. Swidsinski A, Ladhoff A, Pernthaler A, et al. Mucosal flora in Carbohydrate malabsorption syndromes and early signs of
inflammatory bowel disease. Gastroenterology. 2002;122:44–54. mental depression in females. Dig Dis Sci. 2000;45:1255–1259.
14. Fioramonti J, Theodorou V, Bueno L. Probiotics: what are 37. Ledochowski M, Widner B, Bair H, et al. Fructose- and
they? What are their effects on gut physiology? Best Pract Res sorbitol-reduced diet improves mood and gastrointestinal
Clin Gastroenterol. 2003;17:711–724. disturbances in fructose malabsorbers. Scand J Gastroenterol.
15. Goossens D, Jonkers D, Stobberingh E, et al. Probiotics in 2000;35:1048–1052.
gastroenterology: indications and future perspectives. Scand J 38. Ledochowski M, Widner B, Murr C, et al. Fructose
Gastroenterol Suppl. 2003;38:15–23. malabsorption is associated with decreased plasma tryptophan.
16. Shanahan F. Probiotics: a perspective on problems and pitfalls. Scand J Gastroenterol. 2001;36:367–371.
Scand J Gastroenterol Suppl. 2003;38:34–36. 39. Gibson PR, Newnham E, Barrett JS, et al. Review article:
17. Castagliuolo I, Riegler MF, Valenick L, et al. Saccharomyces fructose malabsorption and the bigger picture. Aliment
boulardii protease inhibits the effects of Clostridium difficile Pharmacol Ther. 2007;25:349–363.
toxins A and B in human colonic mucosa. Infect Immun. 1999; 40. Sudo N, Chida Y, Aiba Y, et al. Postnatal microbial
67:302–307. colonization programs the hypothalamic-pituitary-adrenal
18. Madsen K, Cornish A, Soper P, et al. Probiotic bacteria system for stress response in mice. J Physiol. 2004;558:263–275.
enhance murine and human intestinal epithelial barrier 41. Tanida M, Yamano T, Maeda K, et al. Effects of intraduo-
function. Gastroenterology. 2001;121:580–591. denal injection of Lactobacillus johnsonii La1 on renal
19. McCarthy J, O’Mahony L, O’Callaghan L, et al. Double blind, sympathetic nerve activity and blood pressure in urethane-
placebo controlled trial of two probiotic strains in interleukin anesthetized rats. Neurosci Lett. 2005;389:109–114.
10 knockout mice and mechanistic link with cytokine balance. 42. Brown R, Price RJ, King MG, et al. Are antibiotic effects on
Gut. 2003;52:975–980. sleep behavior in the rat due to modulation of gut bacteria?
20. Rachmilewitz D, Katakura K, Karmeli F, et al. Toll-like Physiol Behav. 1990;48:561–565.
receptor 9 signaling mediates the anti-inflammatory effects of 43. Kajander K, Myllyluoma E, Rajilic-Stojanovic M, et al.
probiotics in murine experimental colitis. Gastroenterology. Clinical trial: multispecies probiotic supplementation alleviates
2004;126:520–528. the symptoms of irritable bowel syndrome and stabilizes
21. Jijon H, Backer J, Diaz H, et al. DNA from probiotic bacteria intestinal microbiota. Aliment Pharmacol Ther. 2008;27:48–57.
modulates murine and human epithelial and immune function. 44. Simren M, Ohman L, Olsson J, et al. Clinical trial: the effects
Gastroenterology. 2004;126:1358–1373. of a fermented milk containing three probiotic bacteria in
22. Brenner DM, Moeller MJ, Chey WD, et al. The utility of patients with irritable bowel syndrome-a randomized, double-
probiotics in the treatment of irritable bowel syndrome: a blind, controlled study. Aliment Pharmacol Ther. 2010;31:
systematic review. Am J Gastroenterol. 2009;104:1033–1049; 218–227.
quiz 1050. 45. Czerucka D, Piche T, Rampal P. Review article: yeast as
23. Patrick DL, Drossman DA, Frederick IO, et al. Quality of life probiotics-Saccharomyces boulardii. Alimentary Pharmacology.
in persons with irritable bowel syndrome: development and 2007;26:767–778.
validation of a new measure. Dig Dis Sci. 1998;43:400–411. 46. McFarland LV, Surawicz CM, Greenberg RN, et al. A
24. Park JM, Choi MG, Oh JH, et al. Cross-cultural validation of randomized placebo-controlled trial of Saccharomyces boular-
irritable bowel syndrome quality of life in Korea. Dig Dis Sci. dii in combination with standard antibiotics for Clostridium
2006;51:1478–1484. difficile disease. JAMA. 1994;271:1913–1918.
25. Cann PA, Read NW, Brown C, et al. Irritable bowel 47. Surawicz CM, McFarland LV, Greenberg RN, et al.
syndrome: relationship of disorders in the transit of a single The search for a better treatment for recurrent Clostridium
solid meal to symptom patterns. Gut. 1983;24:405–411. difficile disease: use of high-dose vancomycin combined
26. King TS, Elia M, Hunter JO. Abnormal colonic fermentation with Saccharomyces boulardii. Clin Infect Dis. 2000;31:
in irritable bowel syndrome. Lancet. 1998;352:1187–1189. 1012–1017.
27. Naliboff BD, Munakata J, Fullerton S, et al. Evidence for two 48. Czerucka D, Rampal P. Experimental effects of Saccharomyces
distinct perceptual alterations in irritable bowel syndrome. Gut. boulardii on diarrheal pathogens. Microbes Infect. 2002;4:
1997;41:505–512. 733–739.
28. Whorwell PJ, McCallum M, Creed FH, et al. Non-colonic 49. Dalmasso G, Cottrez F, Imbert V, et al. Saccharomyces
features of irritable bowel syndrome. Gut. 1986;27:37–40. boulardii inhibits inflammatory bowel disease by trapping T
29. Corney RH, Stanton R. Physical symptom severity, psycholo- cells in mesenteric lymph nodes. Gastroenterology. 2006;131:
gical and social dysfunction in a series of outpatients with 1812–1825.
irritable bowel syndrome. J Psychosom Res. 1990;34:483–491. 50. Buts JP, Bernasconi P, Vaerman JP, et al. Stimulation of
30. Fowlie S, Eastwood MA, Ford MJ. Irritable bowel syndrome: secretory IgA and secretory component of immunoglobulins in
the influence of psychological factors on the symptom small intestine of rats treated with Saccharomyces boulardii.
complex. J Psychosom Res. 1992;36:169–173. Dig Dis Sci. 1990;35:251–256.
31. Brandt LJ, Bjorkman D, Fennerty MB, et al. Evidence-based 51. Buts JP, Bernasconi P, Van Craynest MP, et al. Response of
position statement on the management of irritable bowel human and rat small intestinal mucosa to oral administration
syndrome in North America. Am J Gastroenterol. 2002;97:S1–S5. of Saccharomyces boulardii. Pediatr Res. 1986;20:192–196.

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