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Inflammation & Allergy - Drug Targets, 2012, 11, 3-14

A Meta-Analysis and Systematic Review on the Effect of Probiotics in


Acute Diarrhea
1

Pooneh Salari , Shekoufeh Nikfar and Mohammad Abdollahi


1

*,3

Medical Ethics and History of Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran

Department of Pharmacoeconomics and Pharmaceutical Administration, Faculty of Pharmacy, Tehran University of


Medical Sciences; and, Food & Drug Laboratory Research Center, Food & Drug Organization, Ministry of Health &
Medical Education, Tehran 1314715311, Iran
3

Faculty of Pharmacy; and Pharmaceutical Sciences Research Center; and Endocrinology & Metabolism Research
Center, Tehran University of Medical Sciences, Tehran 1417614411, Iran
Abstract: Objectives: Diarrhea the second leading cause of death in childhood is caused by a variety of organisms.
Rehydration reduces the risk of death but it is not effective in shortening duration of disease. Recently, probiotics
have been recommended for prevention or treatment of gastrointestinal disorders including diarrhea. Considering
existing documents from different aspects, it seems that results are somehow controversial or non-conclusive. Thus, we
aimed to meta-analyze clinical trials to show actual benefit of probiotics in treatment of diarrhea.
Methodology: The literature search provided 1228 articles while only 19 articles focusing on the analyses performed
on children were eligible to be included in the meta-analysis with a total of 3867 patients enrolled in the study.
Studies in adults diarrhea, HIV patients, diarrhea induced by Clostridium difficile, radiation and chemotherapy
were also systematically reviewed.
Results: The meta-analysis showed that probiotics decrease the duration of diarrhea and fever significantly in
children while their effects on the duration of hospitalization, vomiting and number of stools per day were not
significant. The results of systematic review on adults diarrhea, amoebiasis, clostridium difficile-associated diarrhea,
diarrhea in HIV positive patients, radiation-induced diarrhea, and chemotherapy-induced diarrhea did not support
efficacy of probiotics in acute diarrhea.
Conclusion: Probiotics may reduce duration of diarrhea and fever in children but their exact efficacy in treatment of
diarrhea is not obvious yet.

Keywords: Clostridium difficile, diarrhea, meta-analysis, probiotics, systematic review.


INTRODUCTION
Diarrhea is considered as one of the most common
gastrointestinal (GI) disorders with high economical impact.
According to the report of the World Health Organization
(WHO), diarrhea is the second leading cause of death in
children under 5 years old which kills around 1.5 million
every year. Diarrhea is characterized by defecating three or
more loose stools per day [1]. Diarrhea can be considered as
a symptom of gastrointestinal infections caused by a variety
of organisms such as virus, bacteria, and parasites. Most of
the time, diarrhea is self-limiting without use of antibiotics.
Regardless of the cause of diarrhea, it is primarily treated by
fluid replacement therapy to restore nutritional defects and
reducing duration of diarrhea. Although, fluid replacement
reduces the risk of dehydration and death but it is not
effective in shortening duration of diarrhea and vomiting.
From 1990s onward, alternative and complementary
medicine have been taken into consideration and nowadays
*Address correspondence to this author at the Faculty of Pharmacy; and
Pharmaceutical Sciences Research Center; and Endocrinology &
Metabolism Research Center, Tehran University of Medical Sciences,
Tehran 1417614411, Iran; Tel/Fax: +98 21 66959104;
E-mail:
Mohammad.Abdollahi@UToronto.Ca
1871-5281/12 $58.00+.00

our pharmacies are full of these types of drugs as well as


nutritional supplements but scientific evidences behind their
usage are insufficient yet. Newly, probiotics have been
recommended for treating or preventing a wide range of GI
disorders including ulcerative colitis [2-4], Crohns disease
[5], and irritable bowel syndrome [6]. Probiotics are live
microorganisms such as bacteria and yeast. Probiotics may
induce luminal effects or induce trophic and antiinflammatory properties. Their luminal effects include
interacting with pathogens and their toxins, maintaining
cellular physiology, and assisting normal microbiota of GI.
Probiotics help in recovering fluid maintenance, aid in
protein and energy production and maturation of
eneterocytes or regulate immune function of the gut [7].
Recently special attention has been paid to their benefits in
acute diarrhea however the results of the several clinical
trials in this field are controversial.
Most of the studies have been carried out on the
effectiveness of probiotics in childrens diarrhea and only a
few were conducted in adults. Therefore, to clarify efficacy
of probiotics in both adults and children, different types of
diarrhea that are caused by rota-virus, amoebiasis,
Clostridium difficile, chemotherapy, and radiation were
evaluated. Furthermore, probiotics were evaluated in the
treatment of diarrhea in human immunodeficiency virus
2012 Bentham Science Publishers

44
1

Inflammation & Allergy - Drug Targets, 2012, Vol. 11, No.

(HIV) positive patients. Existing trials indicated that only


children diarrhea can be meta-analyzed and those of adults
should be critically reviewed.
METHODS
PubMed, Web of Science (ISI), Scopus, and Cochrane
databases were searched by keywords such as probiotics, and
diarrhea. The search was limited to the randomized clinical
trials written in English. The studies entered meta-analysis if
they met the inclusion criteria in conduction of trial on
children with diarrhea. Three reviewers evaluated each
article independently to lessen the probability of duplication,
and better analyzing of reviews, case studies and
uncontrolled trials. Studies were precluded if they were
uncontrolled or their results did not consider our goals.

Salari et al.

and Der Simonian-Laird methods. The Cochrane Q test was


used to test heterogeneity. In case of heterogeneity or
probability of few included studies in meta-analysis, the
random effects for individual and summary of effect size for
weighed mean difference was applied. Funnel plot analysis
was used as publication bias indicator.
RESULTS
The electronic search provided 1228 articles; 176 from
PubMed, 560 from Web of Science, 320 from Scopus, and
172 from Cochrane library. Eighty-nine children studies
were provided in full text, of which, 69 trials didnt fulfill
inclusion criteria and thus only 20 trials were meta-analyzed
(Fig. 1). Totally 3867 subjects enrolled in the study.
Summary of each trial is shown in Table 1.

ASSESSMENT OF TRIAL QUALITY

EFFICACY

Jadad score, which indicates the potentiality of the


studies based on their description of randomization, blinding,
and dropouts (withdrawals) was used to assess the
methodological quality of trials [8]. The quality scale ranged
from 0 to 5 points with a low quality report of score 2 or less
and a high quality report of score at least 3.

Duration of Diarrhea (Day)

STATISTICAL ANALYSIS
Data from selected studies were extracted in the form of
2 2 tables. Included studies were weighted and pooled. Data
were analyzed using StatsDirect software version 2.7.8.
Effect size for weighed mean difference and 95% confidence
intervals (95% CI) were calculated using the Hedges-Olkin

The summary effect size of duration of diarrhea for all


included data for probiotics in comparison to placebo in 19
trials [9-27] was -0.67 with 95% CI= -0.95 to -0.38 (P<
0.0001, Fig. 2a). The Cochrane Q test for heterogeneity
indicated that the studies are heterogeneous (P< 0.0001)
and could not be combined, thus the random effects for
individual and summary for effect size was applied.
Regression of normalized effect vs precision for all included
studies for duration of diarrhea among probiotics vs placebo
therapy was -5.71 (95% CI= -8.99 to
-2.45, P= 0.0018), and Kendalls test on standardized effect
vs
variance indicated tau= -0.49, P= 0.0024 (Fig.
2b).

1228 potentially relevant reports identified and screened for


retrieval from electronic search:
560 from Web of Science
176 from PubMed
320 from Scopus
172 from Cochrane library
540 excluded because of duplication.
397 excluded because they were reviews.
202 excluded on the basis of title and
abstract.
89 reports retrieved
69 reports excluded upon full text search:
n=46: different study design
n=23: did not meet the inclusion criteria

20 eligible randomized controlled clinical trials included in the meta-analysis


Fig. (1). Flow diagram for study selection.

Table 1.

Summary of Placebo Controlled Trials

Author

Duration

Intervention

No. of
Patients

Jadad
Score

Chen et al., [9]

7 days

Bacillus mesentericus, Enterococcus faecalis, Clostridium butyricum/Placebo

293

Moal et al., [10]

3 days

Lactobacillus acidophilus/Placebo

80

Henker et al., [11]

10 days

Escherichia coli Nissle 1917 /Placebo

99

Syzmanski et al., [12]

5 days

Lactobacillus rhamnosus /Placebo

87

Billoo et al., [13]

5 days

Saccharomyces boulardii/Placebo

100

Sarker et al., [14]

5 days

Lactobacillus paracasei /Placebo

203

Salazar-Lindo et al., [15]

5 days

Lactobacillus casei strain GG /Placebo

160

Teran et al., [16]

5 days

75

Narayanappa et al., [17]

14 days

Bifilac /Placebo

80

Basu (1) et al., [18]

7 days

Lactobacillus rhamnosus /Placebo

664

Villarruel et al., [19]

6 days

Saccharomyces boulardii/Placebo

72

Khanna et al., [20]

3 days

Lactobacillus acidophilus /Placebo

98

Kurugol et al., [21]

5 days

Saccharomyces boulardii /Placebo

200

Thibault et al., [22]

5 months

Bifidobactrium breve C50, Streptococcus thermophilus /Placebo

913

Mao et al. [23]

not specified

Streptococcus thermophilus, Bifidobacterium lactis /Placebo

212

Agustina et al., [24]

7 days

Lactobacillus rhamnosus/Placebo

58

Gaon et al., [25]

5 days

Lactobacillus casei, Lactobacillus acidophillus /Placebo

89

Rosenfeldt et al., [26]

5 days

Lactobacillus rhamnosus, Lactobacillus reuteri/Placebo

69

Basu et al., [27]

7 days

Lactobacillus rhamnosus /Placebo

235

Pashapour et al., [28]

not specified

Lactobacillus bulgaris, Streptococcus thernophilus /Placebo

80

Lactobacillus acidophilus, Lactobacillus rhamnosus, Bifidobacterium


longum, Saccharomyces boulardii/Placebo

Bifilac= Streptococcus faecalis, Clostridium butyricum, Bacillus mesentericus, Lactobacillus sporogenes.

Duration of Fever (Hour)


The summary effect size of fever for all included data for
probiotics in comparison to placebo in 4 trials [9, 16, 21, 26]
was -0.18 with 95% CI= -0.34 to -0.02 (P= 0.0246, Fig. 3a).
The Cochrane Q test for heterogeneity indicated that the
studies are not heterogeneous (P= 0.7116) and could be
combined, thus the fixed effects for individual and summary
for effect size was applied. Regression of normalized effect
vs precision for all included studies for fever among
probiotics vs placebo therapy was 1.39 (95% CI= -1.88 to
4.66, P= 0.2096), and Kendalls test on standardized effect
vs variance indicated tau= 0.67, P= 0.33 (Fig. 3b).
Duration of Hospitalization (Day)
The summary effect size of hospitalization for all
included data for probiotics in comparison to placebo in 10
trials [9, 15, 16, 18, 20, 21, 24, 26-28] was -1.12 with 95%
CI= -1.87 to -0.38 (P= 0.0032, Fig. 4a). The Cochrane Q test
for heterogeneity indicated that the studies are heterogeneous
(P< 0.0001) and could not be combined, thus the random
effects for individual and summary for effect size was
applied. Regression of normalized effect vs precision for all
included studies for hospitalization among probiotics vs
placebo therapy was -8.91 (95% CI= -18.84 to 1.01,

P= 0.072), and Kendalls test on standardized effect vs


variance indicated tau= -0.24, P= 0.29 (Fig. 4b).
Duration of Vomiting (Day)
The summary effect size of vomiting for all included data
for probiotics in comparison to placebo in 5 trials [9, 18, 21,
26, 27] was -0.18 with 95% CI= -0.41 to 0.04 (P= 0.1151,
Fig. 5a). The Cochrane Q test for heterogeneity indicated
that the studies are heterogeneous (P= 0.0034) and could not
be combined, thus the random effects for individual and
summary for effect size was applied. Regression of
normalized effect vs precision for all included studies for
vomiting among probiotics vs placebo therapy was -1.01
(95% CI= -10.77 to 8.75, P= 0.76), and Kendalls test on
standardized effect vs variance indicated tau= -0.2, P=
0.4833 (Fig. 5b).
Number of Stools Per Day
The summary effect size of number of stools per day for
all included data for probiotics in comparison to placebo in 3
trials [9, 20, 25] was -0.81 with 95% CI= -2.05 to 0.44 (P=
0.2041, Fig. 6). The Cochrane Q test for heterogeneity
indicated that the studies are heterogeneous (P< 0.0001) and
could not be combined, thus the random effects for

Effect size meta-analysis plot [random effects]


Chen et al., 2010 (9)
Moal et al., 2007 (10)
Henker et al., 2007 (11)
Syzmanski et al., 2006 (12)
Billoo et al., 2006 (13)
Sarker et al., 2005 (14)
Lindo et al., 2004 (15)
Teran et al., 2009 (16)
Narayanappa et al., 2008 (17)
Basu et al., 2007 (1) (18)
Villarruel et al., 2007(19)
Khanna et al., 2005 (20)
Kurugol et al., 2005 (21)
Thibault et al., 2004 (22)
Mao et al., 2008 (23)
Agustina et al, 2007 (24)
Gaon et al., 2003 (25)
Rosenfeldt et al., 2002 (26)
Basu et al., 2007 (2) (27)

-4.0

-2.4

-0.8

0.8

2.4

DL pooled effect size = -0.664639 (95% CI = -0.944865 to -0.384414)

Fig. (2a). Individual and pooled effect size for the outcome of duration of diarrhea in the studies considering probiotics comparing
to placebo therapy.
Bias assessment plot
Standard error
0.0

0.1

0.2

0.3

0.4
-3

-2

-1

1
Effect size

Fig. (2b). Publication bias indicators for the outcome of duration of diarrhea in the studies considering probiotics comparing to
placebo therapy.

Effect size meta-analysis plot [fixed effects]

Chen et al., 2010 (9)

Teran et al., 2009 (16)

Kurugol et al., 2005 (21)

Rosenfeldt et al., 2002 (26)

-0.61

-0.31

-0.01

0.29

0.59

pooled effect size = -0.182353 (95% CI = -0.341399 to -0.023307)

Fig. (3a). Individual and pooled effect size for the outcome of duration of fever in the studies considering probiotics comparing to
placebo therapy.

Bias assessment plot


Standard error
0.10

0.15

0.20

0.25

0.30
-1.0

-0.5

0.0

0.5
Effect size

Fig. (3b). Publication bias indicators for the outcome of duration of fever in the studies considering probiotics comparing to
placebo therapy.

Effect size meta-analysis plot [random effects]


Chen et al., 2010 (9)
Lindo et al., 2004 (15)
Teran et al., 2009 (16)
Basu et al., 2007 (1) (18)
Khanna et al., 2005 (20)
Kurugol et al., 2005 (21)
Agustina et al, 2007 (24)
Pashapour and Lou, 2006 (28)
Rosenfeldt et al., 2002 (26)
Basu et al., 2007 (2) (27)

-6

-4

-2

DL pooled effect size = -1.121195 (95% CI = -1.865857 to -0.376533)


Fig. (4a). Individual and pooled effect size for the outcome of duration of hospitalization in the studies considering probiotics
comparing to placebo therapy.

Bias assessment plot


Standard error
0.000

0.075

0.150

0.225

0.300
-6

-4

-2

2
Effect size

Fig. (4b). Publication bias indicators for the outcome of duration of hospitalization in the studies considering probiotics comparing
to placebo therapy.

Effect size meta-analysis plot [random effects]

Chen et al., 2010 (9)

Basu et al., 2007 (1) (18)

Kurugol et al., 2005 (21)

Rosenfeldt et al., 2002 (26)

Basu et al,.2007 (2) (27) (mean)(day)

-0.90

-0.65

-0.40

-0.15

0.10

0.35

DL pooled effect size = -0.181045 (95% CI = -0.406223 to 0.044133)


Fig. (5a). Individual and pooled effect size for the outcome of duration of vomiting in the studies considering probiotics comparing
to placebo therapy.

Bias assessment plot


Standard error
0.05

0.10

0.15

0.20

0.25
-0.70

-0.45

-0.20

0.05

0.30

0.55
Effect size

Fig. (5b). Publication bias indicators for the outcome of duration of vomiting in the studies considering probiotics comparing to
placebo therapy.

Effect size meta-analysis plot [random effects]

Chen et al., 2010 (9)

Khanna et al., 2005 (20)

Gaon et al., 2003 (25)

-3

-2

-1

DL pooled effect size = -0.80713 (95% CI = -2.052893 to 0.438633)

Fig. (6). Individual and pooled effect size for the outcome of number of stools per day in the studies considering probiotics comparing
to placebo therapy.

individual and summary for effect size was applied.


Regression of normalized effect vs precision for all included
studies for number of stools per day among probiotics vs
placebo therapy could not be calculated because of too few
strata.
DISCUSSION
Diarrhea in Children
The present meta-analysis showed different results in
terms of duration of diarrhea, duration of hospitalization,
duration of fever, duration of vomiting and number of stools
per day. Results indicate that probiotics reduce the duration
of diarrhea and fever while its effect on the duration of
hospitalization, the duration of vomiting and the number of
stools per day is not significant. Previously, Szajewska et al.
(2006) in a meta-analysis reported significant reduction in
the duration of diarrhea, risk of diarrhea, the number of
stools per day, and length of hospitalization [29]. Also, the
results of an older meta-analysis on children's diarrhea
confirmed the benefit of probiotics in reducing the duration
of diarrhea and proposed a dose-effect relationship [30]
which is in agreement with another meta-analysis conducted
in 2002 [31].
Obviously in the most of studies (19 studies), the primary
outcome was the duration of diarrhea while the number and
volume of stools per day were missed. The rest of studies
that evaluated other outcomes do not seem adequate to reach
a conclusion. Chen et al. reported a decrease in the duration
of diarrhea, hospital stay, and presence of gram negative
bacteria in the feces as well as down-regulation of tumor

necrosis factor- (TNF- ) and up-regulation of interleukin


(IL) IL-10, IL-12, and interferon- (IFN- ) in children who
were treated by probiotic [9]. Moreover, probiotics may
decrease duration of diarrhea and fever caused by rotavirus
[32]. However some studies could not confirm the effect of
probiotics on diarrhea [33-35]. Also, none of the studies
reported side effects of probiotics. Noteworthy all included
studies used different types of probiotics which might differ
in their function in the gut. While bifidobacterium colonizes
in the human intestinal microflora, Lactobacillus did not
cause that. It was suggested that Saccharomyces boulardii
may restore healthy microtoba [7]. Regarding these reports
and the results of present analysis, it is rational to suggest
that probiotics decrease the duration of childrens diarrhea
depending on the dose and type of probiotics with no adverse
effect.
Diarrhea in Adults
The available studies in adults are limited and the
outcomes in these studies are far different from children.
Grossi et al. performed a multicenter randomized open-label
parallel group controlled study on the effectiveness of

Lactobacillus paracasei (Flortec ) in comparison with

Lactobacillus GG (FlorVis ) in acute diarrhea for 10 days.


Concerning the duration of diarrhea, they didnt find any
difference in clinical efficacy of these two bacteria. However
91.8% of patients judged in favor of efficacy of Flortec vs
83.7% of patients who were in favor of FlorVis [36].
In another study, Xiao et al. compared the effect of heat

killed (Lacteol ) vs live (Lacidophilin ) Lactobacillus


acidophilus LB in chronic diarrhea. They observed lower

Effect of Probiotics in Acute


Diarrhea

bowel frequency in the Lacteol group before end of two


weeks. At the end of the intervention, improvement in stool
consistency, abdominal pain, and distention was significantly
higher in the Lacteol group. Obviously, no significant
difference was observed when side effects were considered
[37]. Margreiter et al. conducted a multicenter parallel group
randomized double-blind trial on the therapeutic value of a
combination of Lactobacillus gasseri and Bifidobacterium
longum vs Enterococcus faecium in acute diarrhea. In both
groups, the duration of diarrhea was approximately the same
but complete recovery was higher in the bacterium
combination group [38]. Therefore, in adult's diarrhea, the
results of the performed studies do not show the superiority
of probiotics over placebo.
In term of preventing travelers diarrhea, consumption of
Lactobacillus acidophilus showed beneficial effects [39].
Pereg et al. assigned 541 healthy adult males in a placebocontrolled study on yogurt containing Lactobacillus casei
and did not find significant difference between probiotic and
control groups in prevention of diarrhea [40]. Conversely in
the orthopedic rehabilitation elderly population, probiotic
showed significant lower incidence of diarrhea which was
more prominent among participants in age of 80 years or
older [41].
Amoebiasis
The benefits of adding Saccharomyces boulardii to the
standard treatment of invasive amoebiasis were investigated
by Mansour-Ghanaei et al. In their double-blind clinical trial,
the duration of diarrhea, pain and fever decreased in
consumers of probiotic while the duration of headache was
similar in both groups [42].
In an attempt to investigate the anti-diarrheal effect of
probiotics in diarrhea caused by amebiasis, Dinleyici et al.
compared efficacy of Sacccharomyces boulardii with
metronidazole in a randomized open clinical trial. In children
with acute bloody diarrhea caused by Entameba histolytica,
the duration of diarrhea was significantly shorter in
metronidazole plus probiotic along with faster clearance of
amebic cysts [43]; however the results of the study of SavasErdeve et al. was opposing [44].
Clostridium difficile
The clostridium difficile-associated diarrhea is a critical
condition which needs special consideration and antibiotic
treatment for probably a long period of time. Often,
antibiotic regimens fail to prevent recurrence [45, 46].
Therefore restoring the gut microbial flora can prevent
colonization by Clostridium difficile which was observed in
some studies [47-49]. Concerning the importance of
Clostridium difficile-associated diarrhea, Wullt et al.
conducted a double-blind placebo-controlled trial on the
effect of Lactobacillus plantarum on the recurrent diarrhea
caused by clostridium. They could not find significant results
[50].
The effect of two other types of probiotics (Lactobacillus
and Bifidobacterium) in prevention of clostridium difficileassociated diarrhea was studied in a placebo-controlled study
in elderly patients receiving antibiotics. Although in this

Inflammation & Allergy - Drug Targets, 2012, Vol. 11, No. 111
111

study the rate of toxin-positive test and diarrheal symptoms


was higher in the placebo group, more Clostridium difficilepositive patients were identified in the probiotic group. The
authors claimed that their data support toxin neutralization
rather than prevention of colonization [51].
In vitro studies also show controversial results. Naaber et
al. observed strain-specific interaction between Lactobacilli
and Clostridium difficile [52].
HIV
Diarrhea is one of the most common symptoms in HIV
patients [53, 54]. Disease advancement and antiretroviral
therapy increase the risk of diarrhea [55, 56]. The pathology
of diarrhea in HIV patients is unknown and the effectiveness
of several treatment modalities on it is uncertain. Therefore,
after launching probiotics as effective organisms against
diarrhea, limited numbers of investigations were conducted.
Salminen et al. performed a randomized placebo-controlled
study on the effectiveness of Lactobacillus rhamnosus GG
on non-infectious diarrhea in HIV patients and reported no
significant difference between probiotic and placebo groups
in terms of frequency or consistency of diarrhea, HIV RNA
copies, and CD4 cell counts [57]. In a study on HIV-infected
children, Trios et al. determined significant increase in the
mean CD4 count in children receiving Bifidobacterium
bifidum and Streptococcus thermophiles, while no significant
change was seen in stool consistency [58]. In contrast to
previous studies, Anukam et al. indicated the effect of
Lactobacillus rhamnosus and reutri in alleviating diarrhea,
flatulence and nausea in HIV when compared to placebo
[59].
Radiation
In spite of extensive use of highly focused radiation
instruments, diarrheal complications are common in lower
abdomen radiation therapy. Urbancsek et al. evaluated the
efficacy and safety of Lactobacillus rhamnosus in radiationinduced diarrhea and observed significant favorable effects
of Lactobacillus in stool consistency, bowel movement, and
diarrhea rating in comparison with placebo [60]. The results
of the study of Delia et al. confirmed the benefits of
probiotics in prevention of radiation-induced diarrhea. They
used VSL#3 as a probiotic mixture contained Lactobacillus
strains casei, plantarum, acidophilus, delbruekii, and
Bifidobacterium strains longum, breve and infantis and one
strain of Streptococcus salivarius in a double-blind placebocontrolled trial and reported significant less episodes of
diarrhea in patients who underwent radiotherapy [61]. Giralt
et al. evaluated the effect of Lactobacillus casei in a
multicenter placebo-controlled trial but their significant
finding was only seen on stool consistency. According to
their observation, Lactobacillus does not affect incidence of
diarrhea after radiation [62].
In addition to radiotherapy, the effect of probiotics in
chemotherapy-induced diarrhea was evaluated by sterlund
et al. who concluded that Lactobacillus supplementation for
chemotherapy-induced
diarrhea may reduce severity of
diarrhea, and abdominal discomfort [63].

CONCLUSION
Obviously there are major differences in design of
studies or their results. Our review indicates that number of
studies in adults diarrhea or diarrhea caused by radiation,
chemotherapy, and HIV is not adequate to reach a
convincing conclusion. Although, the present meta-analysis
of children studies showed benefits of probiotics in
decreasing the duration of diarrhea and fever, it is notable
that design of the studies, type and dose of the probiotics can
potentially affect the results. From the present review, we
learned that researchers need to agree on definition of
termination of diarrhea and thus design of studies and their
outcome results would be harmonized.
Although no adverse effect was reported in most of
studies, some investigators had concerns about the risk of
fungaemia by S. boulardii especially in HIV or critically ill
patients [64-66].
It is notable that when animal studies [67, 68] or major
reviews [69, 70] are considered, it is clear that diarrhea
might be a symptom of a hidden or undiagnosed
inflammatory bowel disease. The efficacy of probiotics in
such cases return to their potential in regulating body and
intestinal immune status.
Taken together there is still doubt and no sufficient
evidence for the efficacy of probiotics in different types of
diarrhea in children or adults. Therefore, further
investigations on special types of the probiotics, their origin,
their purity, and their combination with prebiotics may be
much helpful.
ACKNOWLEDGEMENT

[9]

[10]

[11]

[12]

[13]

[14]

[15]

[16]

[17]

This paper is the outcome of an in-house non-financially


supported study prepared upon an invitation of Inflammation
& Allergy - Drug Targets.

[18]

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Revised: October 26, 2011

Accepted: November 1, 2011

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