International Journal of Probiotics and Prebiotics Vol. 5, No. 4, pp.
183-192, 2010
ISSN 1555-1431 print, Copyright © 2010 by New Century Health Publishers, LLC
THE EFFECT OF PROBIOTICS IN REDUCING THE DURATION OF ACUTE INFECTIOUS
DIARRHEA IN CHILDREN: A LITERATURE REVIEW
Amber L. Close
School of Nursing, Johns Hopkins University, 525 North Wolfe Street, Baltimore, Maryland 21205, USA
[Received April 2, 2010; Accepted June 9, 2010]
ABSTRACT: Regardless the pathogen, acute infectious diarrhea
can result in severe and even fatal dehydration and electrolyte
imbalances in children. The purpose of this literature review is to
determine the effect of probiotics in reducing the duration of acute
infectious diarrhea specifically in children (age < 18 years) when
compared to standard oral rehydration therapy (ORT) and/or placebo.
Eleven randomized controlled trials published between 2004-2009
met specific inclusion criteria and were included in this review.
Seven (63.6%) of eleven studies were able to show probiotics as being
effective in decreasing the duration of acute infectious diarrhea,
with the two most effective probiotics in shortening the duration of
diarrhea being Lactobacillus rhamnosus GG and Saccharomyces
boulardii. However, due to the heterogeneity of the studies evaluated,
no particular probiotic can be recommended at this time. Therefore,
additional research is necessary to determine which probiotic,
Lactobacillus rhamnosus GG or Saccharomyces boulardii, is more
effective in shortening the duration of acute infectious diarrhea in
children. The goal of future randomized controlled trials is the creation
and design of useful, evidence-based, population specific clinical
guidelines for probiotic treatment regimens in children.
KEY WORDS: Diarrhea, Infectious, Pediatric, Probiotics,
Randomized
Corresponding Author: Amber L. Close, MSN, CRNP, 588 Fratz
Road, Accident, MD 21520 USA; E-mail: amberclose@gmail.com
INTRODUCTION
The World Health Organization (WHO) defines diarrhea as at least
three or more loose or watery stools that take the shape of the container
occurring within a 24 hour period (WHO, 2004). The most important
factor is the consistency of the stools rather than the frequency of bowel
movements. The infecting agents for acute infectious diarrhea include
bacteria, viruses, and/or parasites which invade and destroy intestinal
epithelial cells, thereby altering fluid transportation so that fluid is secreted
abnormally into the bowel lumen while absorption activity is arrested
(Field et al., 1989). Regardless of the microbial etiology, acute infectious
diarrhea in children, which lasts several hours to several days, can quickly
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cause severe and even fatal dehydration and electrolyte imbalances. In
2003, globally an estimated 1.87 million children under the age of five
years died due to diarrhea alone with 80% being two years old and
younger (WHO, 2004). In particular, diarrhea is more prevalent in
developing countries due to difficulties pertaining to the availability of
clean food and water sources and inadequate sanitation infrastructures
(Guerrant et al., 1990). A child in a developing country experiences on
average six to twelve episodes of infectious diarrhea per year, while a
similar child in the United States averages two episodes of infectious
diarrhea per year (Savarino and Bourgeois, 1993). Each episode of
acute infectious diarrhea not only takes a physical toll on the patient, it is
also emotionally and financially taxing to a family, the health care
community, and society.
While prevention of acute infectious diarrhea in children is best, this
is not a feasible approach in many developing countries with limited
resources. Therefore, effective treatment is necessary with goals of
preventing or reversing dehydration, shortening the duration of the
illness, and reducing the infectious period (Allen et al., 2003). One
current treatment option available is antimicrobial medication if the
causative agent is identified to be bacteria or parasites, but rarely is the
causative agent identified. In addition, antimicrobial medication use
adds to the cost of treatment, carries the risk of adverse drug effects, and
increases the likelihood of resistance (WHO, 2004). Another treatment
option, antidiarrheal medication, is discouraged in pediatrics because it
can mask the signs and symptoms of worsening illness (Thielman and
Guerrant, 2004) and it does not prevent or resolve dehydration (WHO,
2004). The treatment option recommended by WHO and UNICEF
is oral rehydration therapy (ORT) (WHO and UNICEF, 2004). ORT
includes the use of oral rehydration salts (ORS) solution containing
glucose and various electrolytes; however, the ORS solution does not
shorten the duration of diarrhea nor does it reduce the stool loss and
may in fact increase stool volume for at least the first few hours of acute
infectious diarrhea in a child (el-Mougi et al., 1994). While ORT is
necessary to replenish lost electrolytes, the use of probiotics in the
treatment regimen for acute infectious diarrhea may decrease the
duration of diarrhea in children. In 2003, the Cochrane Database of
Systematic Reviews published a meta-analysis of 23 studies assessing
probiotics in treating infectious diarrhea in adults and children. The
184 Probiotics and Infectious Diarrhea in Children
meta-analysis found probiotics reduced the mean duration of
diarrhea by 30.48 hours (Allen et al., 2003). Further
investigation into probiotic use, specifically in children, is
warranted because even small reductions in the length of
diarrheal illness in children are important in preventing
detrimental fluid-electrolyte imbalances.
Probiotics are “live microorganisms, which when administered
in adequate amounts, confer a health benefit on the host” (FAO
and WHO, 2001). Currently, the most widely used microbes for
probiotics come from the Bifidobacterium genus and Lactobacillus
genus (Kligler and Cohrssen, 2008). Probiotics are also made from
Saccharomyces boulardii (a non-pathogenic yeast), and less
commonly from Escherichia coli and Bacillus coagulans (Sanders,
2009). The different probiotic species can be further broken down
into various strains. The health benefits of one particular strain
cannot be assumed to hold true with other strains within the same
species (FAO and WHO, 2001). Probiotics are not to be confused
with “live, active cultures” in fermented dairy products. Probiotics
are documented to have a health benefit; whereas, “live, active
cultures” are only tested for their food fermentation properties
(Sanders, 2009). This distinction is important and should be
emphasized through patient education.
To be effective, probiotics must be resistant to stomach acid and
pancreatic-biliary secretions in order to survive the upper gastrointestinal
(GI) transit. Most probiotics do not colonize the lower GI tract for every
long, with resilient probiotic strains cultured from stool only one to two
weeks after ingestion (Doron et al., 2005). Regular ingestion of probiotics
is necessary to maintain colonization. While in the gut, the actual probiotic
mechanism of action is still unknown. It is believed for GI infections
probiotics work by directly competing with the pathogenic
microorganisms in the gut, as well as provide immune modulation and
enhancement (Kligler and Cohrssen, 2008).
There are no absolute contraindications to using probiotics
comprised of Lactobacillus, Bifidobacterium, and Saccharomyces (Kligler
and Cohrssen, 2008). There are no reports of sepsis or other pathologic
conditions from probiotic consumption by healthy individuals. To
date there are no known interactions between probiotics and
medications and other supplements (Kligler and Cohrssen, 2008)
making this treatment option a more viable one for children.
The purpose of this literature review is to determine the effect of
probiotics in reducing the duration of acute infectious diarrhea in
children compared to standard ORT and/or placebo. For health care
providers working in primary care, often in remote areas with limited
resources, information about and an understanding of probiotics
in shortening the duration of pediatric acute infectious diarrhea
will be helpful in improving health outcomes for children. This
review looks at various probiotic species and strains rather than
focusing on just one particular species and strain.
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190 Probiotics and Infectious Diarrhea in Children
METHODS
A literature search was conducted electronically via PubMed,
CINAHL, and EMBASE databases using Boolean operators
AND and OR with key search terms “probiotics”, “acute”,
diarrhea”, and “pediatrics OR child*” as MeSH terms or as
terms within the title and abstract. The literature search was
limited to only include articles written in English and published
within the last five years (2004-2009). This resulted in 60
articles from PubMed, 20 articles from CINAHL, and 96
articles from EMBASE. All 176 articles were exported to
RefWorks®, an online bibliographic management program,
to eliminate 45 article duplicates. In the end, the literature
search yielded 131 unique articles.
All of the titles and abstracts from the 131 articles were reviewed
for inclusion. Studies were included if they were randomized
controlled trials (RCT) examining the use of probiotics in acute
onset infectious diarrhea, not diarrhea related to any chronic GI
conditions or diarrhea associated with antibiotic use. In addition,
the studies had to focus on a pediatric population (age < 18 years)
regardless of ethnicity or sex and had to have diarrhea duration as
an outcome measure. Eleven studies met the inclusion criteria, all
of which are Level I evidence RCTs comparing probiotic
administration to either standard ORT therapy and/or placebo.
Table 1 is an evidence table summarizing the eleven studies’
characteristics including sample populations, settings, interventions,
statistical analyses, and outcomes. The studies’ were evaluated using
the Johns Hopkins Nursing Evidence-Based Practice Model
(Newhouse et al., 2007) to rate the studies’ strength and quality of
evidence. All eleven studies included in this review are Level 1
evidence. Level 1 (out of three) strength of evidence is the highest
distinction, reserved for randomized controlled trials and meta-
analyses of randomized controlled trials. Each article reviewed is
given a scientific evidence quality rating of A, B, or C. “A” indicates
“high quality” scientific evidence due to “consistent results,
sufficient sample size, adequate control, and definitive conclusions;
consistent recommendations based on extensive literature review
that includes thoughtful reference to scientific evidence.” “B”
indicates “good quality” scientific evidence due to “reasonably
consistent results, sufficient sample size, some control, and fairly
definitive conclusions; reasonably consistent recommendations
based on fairly comprehensive literature review that includes some
reference to scientific evidence.” Finally, “C” indicates “low quality
or major flaws” because of “little evidence with inconsistent results,
insufficient sample size, conclusions cannot be drawn.”
RESULTS
Overview of Included Studies
Of the eleven randomized controlled trials evaluating the effects
of probiotics in reducing the duration of acute infectious diarrhea
in children compared to standard ORT and/or placebo, five
focused on Lactobacillus rhamnosus GG (Basu et al., 2007; Basu
et al., 2009; Misra et al., 2009; Salazar-Lindo et al., 2004;
Szymański et al., 2006); four focused on Saccharomyces boulardii
(Billoo et al., 2006; Htwe et al., 2008; Kurugöl and Koturoglu,
2005; Villarruel et al., 2007); one looked at a probiotic
combination of Lactobacillus acidophilus and Bifidobacterium
bifidum (Kianifar et al., 2009); and one final study compared
five different probiotic preparations: (1) Lactobacillus rhamnosus
GG; (2) Saccharomyces boulardii; (3) Bacillus clausii; (4) mix
of L. delbrueckii var. bulgaricus, Streptococcus thermaphilus,
Lactobacillus acidophilus, and Bifidobacterium bifidum; and (5)
Enterococcus faecium SF68 (Canani et al., 2007). The eleven
trials comprised 2802 patients ranging in age from two months
to twelve years. Eight trials were double blinded, one was single
blinded, and two trials the blinding was not specified. The
hospital setting was used for seven trials, two trials were
conducted in the community, and two trials used combined
settings of hospital and community. Control groups used the
following interventions: ORT (Basu et al., 2007; Basu et al.,
2009; Billoo et al., 2006; Canani et al., 2007; Htwe et al.,
2008), placebo (Kurugö and Koturoglu, 2005; Misra et al.,
2009; Szymański et al., 2006; Villarruel et al., 2007), ORT
with placebo (Kianifar et al., 2009), and milk formula (Salazar-
Lindo et al., 2004).
Effect of Probiotics
Six different probiotics formulations were used in the eleven
research trials. In seven of the eleven studies, probiotics were able
to decrease the duration of diarrhea with statistical significance:
one used Lactobacillus rhamnosus GG (Basu et al., 2009), four
used Saccharomyces boulardii (Billoo et al., 2006; Htwe et al., 2008;
Kurugö and Koturoglu, 2005; Villarruel et al., 2007); one
used the Lactobacillus acidophilus and Bifidobacterium bifidum
(Kianifar et al., 2009), and the study comparing five different
probiotic preparations (Canani et al., 2007) revealed Lactobacillus
rhamnosus GG and the probiotic mix as effective. 63.6% (7 out
of 11) of the studies were able to show probiotics as being effective
in decreasing the duration of acute infectious diarrhea in children
when compared to standard ORT and/or placebo. In addition,
there were no complications/adverse effects associated with
probiotic use in any of the reviewed studies. The overall positive
probiotic effect in shortening the duration of acute infectious
diarrhea is despite great variability between the evaluated studies.
The differences amongst the studies were vast. Not only did the
studies use different probiotic types, dosages, dosing frequencies,
treatment lengths, and routes of administration; there was also
heterogeneity amongst the study populations, locations, settings,
and methodology. All of the variability weakens the external
validity so that the research findings are of limited generalizability.
DISCUSSION
Limitations of the Evaluated Studies
As stated earlier, the evaluated studies had great variability. Such
variability contributes to the limitations of the evaluated studies.
In particular, there were multiple definitions for diarrhea and the
cessation of diarrhea. These differing definitions weaken the ability
for comparison across trials. As stated earlier in this review paper,
the WHO (2004) defines diarrhea as at least three or more

loose or watery stools that take the shape of the container
occurring with a 24 hour period. Most studies used the WHO
guidelines. However, Kurugöl and Koturoglu (2005) defined
diarrhea as “stools passed at least twice as frequently than usual”
and Szymański et al. (2006) defined diarrhea as “three or more
bowel movements per day of stools that are looser than normal.”
Two studies (Billoo et al., 2006; Kianifar et al., 2009) did not
define diarrhea, nor did they define the end of diarrhea. For
the two studies by Basu (2007; 2009), the cessation of diarrhea
was defined as “two consecutive soft or formed stools or no
stool for 12 consecutive hours.” Other diarrhea endpoints
included: “normal stool output” (Canani et al., 2007), “less
than three stools per day or stools with a solid consistency only”
(Htwe et al., 2008), “first normal stool” (Kurugöl and
Koturoglu, 2005), “stool frequency less than three per day and
consistency changing toward solid” (Misra et al., 2009),
“passage of formed stool or passage of no stool for twelve
consecutive hours” (Salazar-Lindo et al., 2004), “no abnormal
bowel movements for last twelve hours or the time of second
normal stool” (Szymañski et al., 2006), and “less than three
times a day or the stool consistency improved for at least 24
hours” (Villarruel et al., 2007). These definitions of diarrhea
and the cessation of diarrhea are privy to subjectivity when
observing consistency thereby causing problems with inter-
rater reliability.
Other areas of variability amongst all of the studies include
the use of antibiotics, hydration status, dietary intake during
the trial, and weight/BMI on admission of the study participants
– all of which were possible confounding variables. Additional
limitations include the potential recall bias of parents/guardians
when recalling how long the child had diarrhea prior to
enrollment in the research trials, as well as the inter-rater
reliability issues associated with parental/guardian data
collection of diarrheal episodes. There were no particular
variable limitations that could only be associated with the
statistically significant studies or with the not statistically
significant studies.
Finally, out of the 11 studies reviewed, only five reported
power analyses (Basu et al., 2007; Basu et al., 2009; Canani et
al., 2007; Kianifar et al., 2009; Szymański et al., 2006). Studies
without a power analysis may not have a sample size sufficient
to detect a statistically significant effect.
CONCLUSION
In this review of current evidence, the majority of the studies
demonstrated probiotic use reduced the duration of acute
infectious diarrhea in children. However, due to the
heterogeneity in the studies’ populations, settings, probiotics,
methodology, and outcomes, no particular probiotic can be
recommended for use in decreasing the duration of acute
infectious diarrhea in children across the board; nor is there
enough evidence-based research available to offer
recommendations for practice change. Instead, additional
targeted randomized controlled trials are necessary in order to
Probiotics and Infectious Diarrhea in Children 191
determine the most appropriate probiotic species and strains,
dose, frequency, mode of administration, and treatment length
for specific populations in relation to the age and level of health
(i.e. hydration status, level of nourishment) of children and
infective agent involved.
One particular area of research to consider is comparison of
the effectiveness between different probiotics. While additional
research is being conducted on very specific populations with
specific probiotic species, the evidence that is currently available
can be used to compare probiotics. Since the oral glucose-electrolyte
rehydration solution recommended by WHO and UNICEF as
rehydration therapy neither shortens the duration of diarrheal
illness nor does it reduce stool loss (el-Mougi et al., 1994), and
probiotics in general were found to decrease the mean duration of
acute infectious diarrhea in adults and children (Allen et al., 2003),
a comparison of two probiotics from this literature review would
be appropriate to determine which one is more efficacious in
reducing the duration of acute infectious diarrhea in children.
The two most effective probiotics in shortening the duration in
diarrhea from this literature review were Lactobacillus rhamnosus
GG and Saccharomyces boulardii. The data and results from future
randomized controlled trials will be helpful in the creation and
design of useful, evidence-based, population specific clinical
guidelines for probiotic treatment regimens for children.
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