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Probiotics
Theresa L. Charrois, BSc
Pharm, MSc,* Gagan
Sandhu,* Sunita Vohra,
MD, MSc*
Author Disclosure
Ms Charrois, Ms
Sandhu, and Dr Vohra
did not disclose any
financial relationships
relevant to this
article.
Complementary and Alternative Medicine: A New Series
Pediatrics in Review is happy to present a new series. It is difficult to define complementary and
alternative medicine, but one perspective would be to include methods of treating or prevent-
ing disease or improving wellness that have arisen from sources of experience and research
different from those traditionally taught in most medical schools and that have not been
incorporated into current practice by traditional practitioners. Many of these therapies have
arisen from the background of herbal use.
The series was proposed by Dr Sunita Vohra, Director of the Complementary and Alterna-
tive Research and Education Program at the University of Alberta, Canada, and the initial
articles will be written by Dr Vohra and her colleagues in cooperation with the Provisional
Section on Contemporary, Holistic, and Integrative Medicine of the American Academy of
Pediatrics (AAP SCHIM).
Dr Kathi Kemper, a member of the AAP who is a leading educator in the realm of holistic
and alternative medicine and who has been involved in establishing this series, urges colleagues
to focus not on the tradition from which any therapy emerges, but on whether the therapy has
been studied and proven. It is in the spirit of examining these therapies, which might appear
unfamiliar and unusual, with a scientific eye and an open mind that we present these articles,
starting with a discussion of probiotics. Significant numbers of our patients are using
alternative therapies, usually on their own, and it is important for us to educate ourselves as to
what is known about them.—LFN
Introduction
Increasing evidence supports the use of probiotics to treat and prevent gastrointestinal
(GI) disorders. The rationale behind probiotics usage is their ability to normalize microbial
flora.
Definition and Description
Probiotics are nonpathogenic microbes, usually of the lactic acid-producing variety, that
are used to improve or normalize the balance of gut microflora. They are available as
dietary supplements or in food products (eg, yogurt) as live active culture. A variety of
probiotic supplements are available, but Lactobacillus GG, Bifidobacterium, and Sac-
charomyces sp have been studied most extensively. Increasing evidence supports the use
of probiotics to prevent and treat various GI disorders such as irritable bowel
syndrome, inflammatory bowel disease, acute gastroenteritis, and antibiotic-related
diarrhea.
Although probiotic preparations are used commonly worldwide, specific use data for
children are unavailable.
Evidence of Efficacy in Pediatrics
A number of systematic reviews (Table) have evaluated the use of probiotic supplements to
treat diarrhea. Additionally, numerous randomized, controlled trials have examined their
use in constipation, irritable bowel syndrome, Crohn disease, ulcerative colitis, atopy and
eczema, Helicobacter pylori colonization and eradication, pancreatitis, cirrhosis, radiation-
induced diarrhea, necrotizing enterocolitis, prophylaxis against bacterial sepsis, and uri-
nary tract infections in preterm infants. (6)(7) More data are necessary before probiotics
can be recommended as primary therapeutic agents for these disorders.
*Complementary and Alternative Research and Education (CARE) Program, Department of Pediatrics, University of Alberta,
Canada, on behalf of the American Academy of Pediatrics Provisional Section on Complementary, Holistic, and Integrative
Medicine.
Article gastroenterology
Pediatrics in Review Vol.27 No.4 April 2006 137
Common empiric uses that have not yet been studied
formally include acne, canker sores, colon cancer, heart
disease, nonalcoholic fatty liver, and thrush.
Evidence of Safety
Clinical trials have not revealed major adverse effects of
probiotics in healthy individuals, and long-term con-
sumption also appears to be safe and well tolerated.
However, there are case reports of aggravation of exist-
ing symptoms, septicemia, pneumonia, and meningitis in
severely debilitated, immunocompromised children and
in neonates. (8) The safest forms of probiotic bacteria are
found in fermented foods, including buttermilk, yogurt,
kefir, and sauerkraut. However, supplemental forms usu-
ally provide higher doses of probiotic bacteria.
Some probiotics (L acidophilus, Lactobacillus GG,
Saccharomyces sp) have been found safe for use in chil-
dren if administered in appropriate doses. Usage has
been evaluated in randomized, controlled trials for chil-
dren as young as 1 month of age.
Information is insufficient to recommend safe probi-
otic supplement usage by women who are pregnant or
lactating. Usage of probiotic-containing foods in this
population generally is considered safe.
Pharmacologic Action
Probiotics are believed to modulate immune activity via
differential activation of epithelial and immune cell re-
ceptors. Postulated mechanisms of action include inhibi-
tion of adhesion and invasion by enteroinvasive species
into enteric cells, colonization of the gut, enhancement
of epithelial cytoprotection, and destruction of receptor
sites for toxins.
Administration/Dosage Forms
The investigated dosages range from 1 million to 300
billion colony-forming units per day. Probiotic supple-
ments usually are administered as capsules or powder.
There is significant discrepancy in the literature as to
appropriate doses in children, and the dose varies accord-
ing to probiotic. Moreover, variations are significant
between and within products because production gener-
ally is not standardized. Stability is an issue with most
probiotic preparations; some may require refrigeration
and others (such as S boulardii, which is a yeast product)
may not. Patients should be instructed to consider this
when selecting a product. Some products can be sprin-
kled on food or dissolved in beverages, which aids in
administration to children. However, because some pro-
Table. Summary of Systematic Reviews of Probiotics in Children
Citation
Patient Population and
Study Design Results Conclusions
Allen et al, 2002 (1)
Probiotics for treating
infectious diarrhea
Adults and children
RCTs (nⴝ23 studies)
Risk of diarrhea at 3 days:
RR 0.66; 95% CI 0.55,
0.77 (favor probiotics)
Promising results; significant
heterogeneity of methods
and outcomes
D’Souza et al, 2002 (2)
Probiotics in prevention of
antibiotic-associated
diarrhea: meta-analysis
Adults and children
R, DB, PC trials
(nⴝ9 studies)
Patients free of diarrhea:
OR 0.37, 95% CI 0.26,
0.53 (favor probiotics)
Positive results; no information
regarding adverse events
Huang et al, 2002 (3)
Efficacy of probiotic use
in acute diarrhea in
children: a meta-analysis
Children <5y
Controlled clinical trials
(nⴝ18 studies)
Reduction of diarrhea:
ⴚ0.8 days, 95% CI
ⴚ1.1, ⴚ0.6 days
(favor probiotics)
Significant heterogeneity of
methods and outcomes; less
rigorous systematic review
Cremonini et al, 2002 (4)
The effect of probiotic
administration on
antibiotic-associated
diarrhea: a meta-analysis
Adults and children
RCTs (nⴝ22 studies)
Presence of diarrhea at
end of treatment: RR
0.40, 95% CI 0.27,
0.57 (favor probiotics)
Positive effects; some
methodologic problems such
as unclear inclusion and
exclusion criteria
Szajewska et al, 2001 (5)
Probiotics in the
treatment and prevention
of acute infectious
diarrhea in infants and
children
Infants and children
RCTs (nⴝ10 studies)
Risk of diarrhea: RR 0.40,
95% CI 0.28, 0.57
(favor probiotics)
Only
Lactobacillus
GG showed
consistent benefit (other
studies included
L reuteri,
S boulardii, L acidophilus
)
RCT⫽randomized controlled trial, R⫽randomized, DB⫽double-blind, PC⫽placebo-controlled, RR⫽relative risk, OR⫽odds ratio, 95% CI⫽95% confi-
dence interval.
gastroenterology probiotics
138 Pediatrics in Review Vol.27 No.4 April 2006
biotics are sensitive to gastric acid and bile, they should
be administered on an empty stomach. This property is
product-specific, and patients should refer to the labeling
instructions. Treatment often is initiated at the same time
as antibiotic therapy to prevent antibiotic-associated di-
arrhea. The duration of treatment varies from 1 to
4 weeks following resolution of symptoms.
References
1. Allen SJ, Okoko B, Martinez E, Gregorio G, Dans LF. Probiot-
ics for treating infectious diarrhoea. Cochrane Database Syst Rev.
2003;4:CD003048
2. D’Souza AL, Rajkumar C, Cooke J, Bulpitt CJ. Probiotics in
prevention of antibiotic-associated diarrhoea: meta-analysis. BMJ.
2002;324:1361–1366
3. Huang JS, Bousvaros A, Lee JW, Diaz A, Davidson EJ. Efficacy
of probiotic use in acute diarrhea in children: a meta-analysis. Dig
Dis Sci. 2002;47:2625–2634
4. Cremonini F, Di Caro S, Nista EC, et al. Meta analysis: the effect
of probiotic administration on antibiotic-associated diarrhoea. Ali-
ment Pharmacol Ther. 2002;16:1461–1467
5. Szajewska H, Mrukowicz JZ. Probiotics in treatment and pre-
vention of acute infectious diarrhea in infants and children: a
systematic review of published randomized, double-blind placebo-
controlled trials. J Pediatr Gastroenterol Nutr. 2001;33(suppl 2):
S17–S25
6. Probiotics. Natural Standard Monograph. Natural Standard
2005. Available at: www.naturalstandard.com. Accessed November
2005
7. Kullen MJ, Bettler J. The delivery of probiotics and prebiotics to
infants. Curr Pharm Des. 2005;11:55–74
8. Salminen S, von Wright A, Morelli L, et al. Demonstration of
safety of probiotics – a review. Int J Food Microbiol. 1998;44:
93–106
Question From the Clinician
Experienced clinicians and specialists have much to teach us. Our Question From the
Clinician column offers readers an opportunity to submit questions regarding problems
they have encountered in their clinical practice to experts in the field. We welcome your
letters.
—LFN
gastroenterology probiotics
Pediatrics in Review Vol.27 No.4 April 2006 139