See discussions, stats, and author profiles for this publication at: https://www.researchgate.

net/publication/287917972

World Gastroenterology Organisation practice guideline: Probiotics and

prebiotics - May 2008

Article  in  South African Gastroenterology Review · August 2008

CITATIONS READS

110 3,460

14 authors, including:

Francisco Guarner Aamir Khan

University Hospital Vall d'Hebron Glocal University
330 PUBLICATIONS   39,502 CITATIONS    31 PUBLICATIONS   1,887 CITATIONS   

SEE PROFILE SEE PROFILE

Rami Eliakim Alfred Gangl

Sheba Medical Center Medical University of Vienna
613 PUBLICATIONS   23,445 CITATIONS    352 PUBLICATIONS   10,805 CITATIONS   

SEE PROFILE SEE PROFILE

Some of the authors of this publication are also working on these related projects:

Madsen lab View project

Biologics for IBD View project

All content following this page was uploaded by Juan Andres De Paula on 21 January 2016.

The user has requested enhancement of the downloaded file.

 WGO GUIDELINE

World Gastroenterology Organisation Global Guidelines

Probiotics and Prebiotics
October 2011

Review Team, Francisco Guarner, MD (Chair, Spain), Aamir G. Khan, MD (Pakistan),

James Garisch, MD (South Africa), Rami Eliakim, MD (Israel), Alfred Gangl, MD (Austria),
Alan Thomson, MD (Canada), Justus Krabshuis (France), Ton Lemair, MD (The Netherlands),
Invited outside experts, Pedro Kaufmann, MD (Uruguay), Juan Andres de Paula, MD (Argentina),
Richard Fedorak, MD (Canada), Fergus Shanahan, MD (Ireland), Mary Ellen Sanders, PhD (USA),
Hania Szajewska, MD (Poland), Balakrishnan Siddartha Ramakrishna, MD (India),
Tarkan Karakan, MD (Turkey), and Nayoung Kim, MD (South Korea)

CONTENTS
1 Probiotics—the concept 2
2 Products, health claims, and commerce 3
3 Probiotics—the science 6
4 Clinical applications 6
5 Probiotics, prebiotics, and evidence—the global picture 13

List of tables
Table 1 Definitions used by the international scientific associations for probiotics and prebiotics 2
Table 2 Definitions 2
Table 3 Nomenclature for microorganisms 3
Table 4 Examples of probiotic strains in products 4
Table 5 Information on suppliers of probiotics and prebiotics 5
Table 6 Human intestinal microbiota. The gut microbiota form a diverse and dynamic ecosystem, including bacteria, Archaea, and
Eukarya that have adapted to live on the intestinal mucosal surface or within the gut lumen 6
Table 7 Mechanisms of probiotic/host interaction. Symbiosis between microbiota and the host can be optimized by pharmacological or
nutritional interventions in the gut microbial ecosystem using probiotics or prebiotics 7
Table 8 Evidence-based pediatric indications for probiotics and prebiotics in gastroenterology 8
Table 9 Evidence-based adult indications for probiotics and prebiotics in gastroenterology 10
List of figures
Figure 1 Electron micrograph of Lactobacillus salivarius 118 adhering to Caco-2 cells 2
Figure 2 Spectrum of interventions that can affect health and disease 3
Figure 3 The normal microbiota and probiotics interact with the host in metabolic activities and immune function and prevent
colonization of opportunistic and pathogenic microorganisms 7

From the University Hospital Vall d’Herbron, Barcelona, Spain.

F.G. is employed by the Hospital Vall d’Hebron as Consultant Gastroenterologist. The other authors declare that they have nothing to disclose.
Reprints: Francisco Guarner, MD (Chair, Spain), Hospital Vall d’Hebron, Passeig Vall d’Hebron, 119-129, 08035 Barcelona, Spain (e-mail:
fguarnera@medynet.com).
Copyright r 2012 by Lippincott Williams & Wilkins

468 | www.jcge.com J Clin Gastroenterol  Volume 46, Number 6, July 2012

J Clin Gastroenterol  Volume 46, Number 6, July 2012 WGO Global Guideline: Probiotics and Prebiotics

PROBIOTICS—THE CONCEPT
History and Definitions
A century ago, Elie Metchnikoff (a Russian scientist,
Nobel laureate, and professor at the Pasteur Institute in
Paris) postulated that lactic acid bacteria (LAB) offered
health benefits capable of promoting longevity. He sug-
gested that “intestinal autointoxication” and the resultant
aging could be suppressed by modifying the gut microbiota
and replacing proteolytic microbes such as Clostridium—
which produce toxic substances including phenols, indoles,
and ammonia from the digestion of proteins—with useful
microbes. He developed a diet with milk fermented with the
bacterium he called “Bulgarian bacillus.”
In 1917, before Sir Alexander Fleming’s discovery of
penicillin, the German professor Alfred Nissle isolated a
nonpathogenic strain of Escherichia coli from the feces of
a First World War soldier who did not develop enterocolitis
during a severe outbreak of shigellosis. Disorders of the
intestinal tract were frequently treated with viable non-
pathogenic bacteria to change or replace the intestinal FIGURE 1. Electron micrograph of Lactobacillus salivarius 118
ssmicrobiota. The E. coli strain Nissle 1917 is one of the few adhering to Caco-2 cells. Neurogastroenterology and Motility: the
examples of a non-LAB probiotic. Official Journal of the European Gastrointestinal Motility Society
Bifidobacterium was first isolated by Henry Tissier (of by European Gastrointestinal Motility Society. Reproduced with
the Pasteur Institute) from a breastfed infant, and he named permission of Blackwell Publishing Ltd. in the format Journal
the bacterium Bacillus bifidus communis. Tissier claimed through Copyright Clearance Center.
that bifidobacteria would displace the proteolytic bacteria
that cause diarrhea and recommended the administration of agricultural materials (cereals, roots, tubers, fruit and vege-
bifidobacteria to infants suffering from this symptom. tables, milk, meat, fish, etc.) (Table 2).
The term “probiotics” was first introduced in 1965 by Prebiotics and Synbiotics
Lilly and Stillwell; in contrast to antibiotics, probiotics were
Prebiotics are dietary substances (mostly consisting of
defined as microbially derived factors that stimulate the
nonstarch polysaccharides and oligosaccharides poorly di-
growth of other organisms (Table 1). In 1989, Roy Fuller
gested by human enzymes) that nurture a selected group of
emphasized the requirement of viability for probiotics and
microorganisms living in the gut. They favor the growth of
introduced the idea that they have a beneficial effect on the
beneficial bacteria over that of harmful ones.
host.
Unlike probiotics, most prebiotics are used as food
ingredients—in biscuits, cereals, chocolate, spreads, and dairy
What Are Probiotics?
products, for example. Commonly known prebiotics are:
Probiotics are live microbes that can be formulated  Oligofructose
into many different types of product, including foods, drugs,  Inulin
and dietary supplements. Species of Lactobacillus (Fig. 1)  Galactooligosaccharides
and Bifidobacterium are most commonly used as probiotics,  Lactulose
but the yeast Saccharomyces cerevisiae and some E. coli and  Breast milk oligosaccharides
Bacillus species are also used as probiotics. LAB, including
Lactobacillus species, which have been used for preservation
of food by fermentation for thousands of years, can serve a TABLE 2. Definitions
dual function by acting as agents for food fermentation and,
LAB A functional classification of nonpathogenic,
in addition, potentially imparting health benefits. Strictly nontoxigenic, gram-positive, fermentative
speaking, however, the term “probiotic” should be reserved bacteria that are associated with the production
for live microbes that have been shown in controlled human of lactic acid from carbohydrates, making them
studies to impart a health benefit. Fermentation of food pro- useful for food fermentation. Species of
vides characteristic taste profiles and lowers the pH, which Lactobacillus, Lactococcus, and Streptococcus
prevents contamination by potential pathogens. Fermenta- thermophilus are included in this group. As the
tion is globally applied in the preservation of a range of raw genus Bifidobacterium is not associated with food
fermentation and is taxonomically distinct from
the other LABs, it is not usually grouped as a
TABLE 1. Definitions Used by the International Scientific member of the LABs. Many probiotics are also
Associations for Probiotics and Prebiotics LABs, but some probiotics (such as certain strains
of Escherichia coli, spore formers, and yeasts used
Probiotics Live microorganisms that confer a health benefit on the as probiotics) are not
host when administered in adequate amounts Fermentation A process by which a microorganism transforms
Prebiotic Selectively fermented ingredients that result in specific food into other products, usually through the
changes in the composition and/or activity of the production of lactic acid, ethanol, and other
gastrointestinal microbiota, thus conferring benefit(s) metabolic end products
upon host health
Synbiotics Products that contain both probiotics and prebiotics LAB indicates lactic acid bacteria.

r 2012 Lippincott Williams & Wilkins www.jcge.com | 469

Guarner et al J Clin Gastroenterol  Volume 46, Number 6, July 2012

Lactulose is a synthetic disaccharide used as a drug

for the treatment of constipation and hepatic encephalo- TABLE 3. Nomenclature for Microorganisms
pathy. The prebiotic oligofructose is found naturally in Genus Species Strain Designation
many foods, such as wheat, onions, bananas, honey, garlic, Lactobacillus rhamnosus GG
and leeks. Oligofructose can also be isolated from chicory Lactobacillus casei DN-114 001
root or synthesized enzymatically from sucrose.
Fermentation of oligofructose in the colon results in a
large number of physiological effects, including:
 Increasing the numbers of bifidobacteria in the colon.
 Increasing calcium absorption. Health Claims
 Increasing fecal weight. Probiotics are intended to assist the body’s naturally
 Shortening gastrointestinal transit time. occurring gut microbiota. Some probiotic preparations
 Possibly, lowering blood lipid levels. have been used to prevent diarrhea caused by antibiotics, or
The increase in colonic bifidobacteria has been as- as part of the treatment for antibiotic-related dysbiosis.
sumed to benefit human health by producing compounds to Studies have documented probiotic effects on a variety of
inhibit potential pathogens, by reducing blood ammonia gastrointestinal and extraintestinal disorders, including in-
levels, and by producing vitamins and digestive enzymes. flammatory bowel disease, irritable bowel syndrome (IBS),
Synbiotics are appropriate combinations of prebiotics vaginal infections, and immune enhancement. Some pro-
and probiotics. A synbiotic product exerts both a prebiotic biotics have been shown to increase survival of preterm
and probiotic effect. neonates. Probiotics have also been investigated in relation
to atopic eczema and complications of liver cirrhosis. Al-
though there is some clinical evidence for the role of pro-
Genera, Species, and Strains biotics in lowering cholesterol, the results are conflicting.
Probiotic research suggests a range of potential health In general, the strongest clinical evidence for pro-
benefits. However, the effects described can only be attrib- biotics is related to their use in improving gut health and
uted to the strain or strains tested, and not to the species or stimulating immune function.
the whole group of LABs or other probiotics.
The implications of the strain specificity of effects are: Justification—Research and Proof
 Documentation of health effects must be conducted on Claims of benefit for probiotics can take different
the specific strain being sold in the product. forms, depending on the intended use of the product. The
 Results and review articles from studies conducted on most common claims are those that relate probiotics to the
specific strains cannot be used as evidence to support normal structure and functioning of the human body,
health effects of untested strains. known as “structure-function claims.” Often considered
 Studies that document the efficacy of specific strains at a “soft” claims, as no mention of disease or illness is allowed,
specific dosage are not sufficient evidence to support these claims still have to be substantiated by consistent re-
health effects at a lower dosage. sults from well-designed, double-blind, placebo-controlled
The role of the vehicle/filler substances in delivering human studies. In vitro and animal studies, although im-
functional benefits also has to be taken into account. Some portant in developing clinical strategies, are not considered
effects may not be reproduced using a different vehicle/filler— sufficient to document such claims.
for instance, because of reduced viability of the strain. The Council for Agricultural Science and Technology
A probiotic strain is identified by the genus, species, and (http://www.cast-science.org) has published a paper on
an alphanumeric designation. In the scientific community, probiotics that makes the following statements concerning
there is an agreed nomenclature for microorganisms—for product claims:
example, L. casei DN-114 001 or L. rhamnosus GG (Table 3).  It is unfortunate that products can currently be labeled
Marketing and trade names are not regulated, and as probiotics without being either well defined or sub-
companies can call their products’ probiotics whatever they stantiated with controlled human studies.
want—for example, LGG.  The pace of research into probiotics has accelerated in
recent years: in 2001 to 2005, more than 4 times as many
human clinical trials on probiotics were published as in
PRODUCTS, HEALTH CLAIMS, AND COMMERCE 1996 to 2000.
 There are significant gaps for some products between
Market Potential what research has shown to be effective and what is
High-profile probiotic-containing products have been claimed in the marketplace.
hugely successful in Europe, Asia, and, more recently, in  Failures of products to meet label claims with regard
other regions of the world. This marketing success will pro- to the numbers and types of viable microbes present in
mote consumption, product development, and research. the product, and about the quantity that needs to be
Probiotics are often recommended by nutritionists and consumed for a health benefit, have been documented.
sometimes by doctors, and a range of product types are  The guidelines for examining the scientific evidence on
available in the market (Fig. 2). the functional and safety aspects of probiotics in food

Food Meal Dietary Neutra- Over-the- Prescription

replacement supplement ceutical counter drug
drug

FIGURE 2. Spectrum of interventions that can affect health and disease.

470 | www.jcge.com r 2012 Lippincott Williams & Wilkins

J Clin Gastroenterol  Volume 46, Number 6, July 2012 WGO Global Guideline: Probiotics and Prebiotics

with the number of viable cells of each probiotic strain

TABLE 4. Examples of Probiotic Strains in Products that will remain up to the end of shelf life.
Strain (Alternative
Designations) Brand Name Producer Products: Dosages and Quality
Bifidobacterium animalis Activia Danone/Dannon The most common forms for probiotics are dairy
DN-173 010 products and probiotic-fortified foods (Table 4). However,
Bifidobacterium animalis subsp. Chr. Hansen — tablets, capsules, and sachets containing the bacteria in
lactis Bb-12 freeze-dried form are also available.
Bifidobacterium breve Yakult Bifiene Yakult The dose needed for probiotics varies greatly depend-
Bifidobacterium infantis 35624 Align Procter & ing on the strain and product. Although many over-the-
Gamble counter products deliver in the range of 1 to 10 billion cfu/
Bifidobacterium lactis HN019 Howaru Bifido Danisco dose, some products have been shown to be efficacious
(DR10)
Bifidobacterium longum BB536 — Morinaga Milk
at lower levels, whereas some require substantially more.
Industry For example, Bifidobacterium infantis 35624 was effective in
Enterococcus LAB SF 68 Bioflorin Cerbios-Pharma alleviating the symptoms of IBS at 100 million cfu/d, where-
Escherichia coli Nissle 1917 Mutaflor Ardeypharm as studies with VSL#3 have used sachets with 300 to 450
Lactobacillus acidophilus LA-5 — Chr. Hansen billion cfu 3 times daily. It is not possible to state a general
Lactobacillus acidophilus — Danisco dose that is needed for probiotics; the dosage has to be
NCFM based on human studies showing a health benefit.
Lactobacillus casei Actimel, Danone/Dannon Despite the existing scientific consensus, there is no legal
DN-114 001 DanActive definition of the term “probiotic.” The minimum criteria that
Lactobacillus casei CRL431 — Chr. Hansen
have to be met for probiotic products are that the probiotic
Lactobacillus casei F19 Cultura Arla Foods
Lactobacillus casei Shirota Yakult Yakult must be:
Lactobacillus johnsonii La1 LC1 Nestlé  Specified by genus and strain—research on specific probiotic
(Lj1) strains cannot be applied to any product marketed as a
Lactococcus lactis L1A Norrmejerier — probiotic.
Lactobacillus plantarum 299V GoodBelly, NextFoods  Alive.
ProViva Probi  Delivered in adequate dose through the end of shelf life
Lactobacillus reuteri DSM L. reuteri BioGaia (with minimal variability from one batch to another).
17938 Protectis  Shown to be efficacious in controlled human studies.
Lactobacillus rhamnosus ATCC Vifit and Valio
 Safe for the intended use.
53013 (LGG) others
Lactobacillus rhamnosus LB21 Verum Norrmejerier As there are no universally established and/or enforced
Lactobacillus salivarius — — standards for content and label claims on products, the
UCC118 industry (Table 5) should maintain integrity in formulating
Saccharomyces cerevisiae DiarSafe, Wren and labeling the products so that consumers can have
(boulardii) lyo Ultralevure, Laboratories, confidence in this product category.
etc. Biocodex, etc.
Tested as mixture Product Safety
Lactobacillus acidophilus Bio K + Bio K +  Some species of lactobacilli and bifidobacteria are normal
CL1285 and Lactobacillus International
residents of, or common transients through, the human
casei Lbc80r
Lactobacillus rhamnosus FemDophilus Chr. Hansen digestive system and as such do not display infectivity or
GR-1 and Lactobacillus toxicity.
reuteri RC-14  Traditional LAB, long associated with food fermenta-
VSL#3 (mixture of 1 strain of VSL#3 Sigma-Tau tion, are generally considered safe for oral consumption
Streptococcus thermophilus, Pharmaceuti- as part of foods and supplements for the generally healthy
4 Lactobacillus species, and cals Inc. population and at levels traditionally used.
3 Bifidobacterium species  Regulations for dietary supplements are nonexistent in
strains many countries, or much less strict than those that apply
Lactobacillus acidophilus — —
CUL60 and
for prescription drugs.
Bifidobacterium bifidum  Currently, the Food and Drug Administration in the
CUL 20 United States has not been petitioned for (and therefore
Lactobacillus helveticus A’Biotica and Institut Rosell has not ruled on) any claims for probiotics that relate
R0052 and Lactobacillus others probiotics to a reduction in the risk of disease. Structure-
rhamnosus R0011 function claims are commonly used for probiotics, but
Bacillus clausii strains O/C, Enterogermina Sanofi-Aventis these do not require approval by the Food and Drug
NR, SIN, and T Administration for use.
 Dietary supplement production varies among manufac-
turers, and perhaps over time with the same manufac-
[Food and Agriculture Organization/World Health turer. Efficacy and side effects are likely to differ among
Organization (FAO/WHO) 2002], should be used as a strains, products, brands, or even within different lots
starting point for governments to devise their own policy of the same brand. Products purchased may not be
with regard to new probiotic strains to be introduced for identical with the form used in research.
human use.  Long-term effects of most dietary supplements, other
 It is suggested that manufacturers label the genus, than vitamins and minerals, are not known. Many dietary
species, and strain for each probiotic in a product, along supplements are not used long term.

r 2012 Lippincott Williams & Wilkins www.jcge.com | 471

Guarner et al J Clin Gastroenterol  Volume 46, Number 6, July 2012

TABLE 5. Information on Suppliers of Probiotics and Prebiotics

Company Description URL
BioGaia Lactobacillus reuteri culture comes in 3 different, producer-friendly forms: http://www.biogaia.com
freeze-dried powder, freeze-dried Direct Vat Set (DVS) granules,
and frozen pellets
Bio K + Producer and seller of probiotic mix including Lactobacillus acidophilus http://www.biokplus.com
and Lactobacillus casei
Chr. Hansen The “nu-trish” brand probiotic culture range consists of Probio-Tec, Yo-Fast, http://www.chr-hansen.com
and other nu-trish culture blends with a well-defined viscosity profile
that ferment quickly
Cerbios-Pharma Producer of Enterococcus LAB SF 68 http://www.cerbios.ch
Danisco The company’s cultures division produces, develops, and markets starter cultures, http://www.danisco.com
media, coagulants, and enzymes for cheese, fresh dairy, and other food products,
and also supplies probiotic cultures for foods and supplements, as well as
natural food protectants
Danone Producer of several brands of fermented dairy products containing probiotics http://www.danone.com
DSM The Lafti line of probiotics is formulated for stability, survivability, http://www.dsm.com
and concentration, and includes Lactobacillus acidophilus (Lafti L10),
Lactobacillus casei (Lafti L26), and Bifidobacterium (Lafti B94)
GTC Nutrition NutraFlora short-chain fructooligosaccharides (scFOS) are a cane http://www.gtcnutrition.com
sugar or beet sugar-derived natural prebiotic fiber
Lallemand This Canadian supplier delivers probiotics and biosupplements to the http://www.lallemand.com
nutraceuticals, functional foods, and pharmaceuticals industries
National Starch The Hi-maize brand corn-based resistant starch has multiple benefits, http://www.hi-maize.com
including acting as a prebiotic for digestive health
Orafti BeneoSynergy1 is the unique, patented oligofructose-enriched inulin http://www.orafti.com
prebiotic used in the landmark SynCan project on synbiotics and colon cancer
Probi This biotech company develops and patents probiotic strains, including http://www.probi.com
Lactobacillus plantarum 299v and Lactobacillus rhamnosus 271.
Lactobacillus plantarum 299 has not yet been commercialized, but it is in
the out-licensing phase
Proctor & Gamble “Align” is a probiotic supplement produced by P&G. Align capsules http://www.aligngi.com
contain Bifidobacterium infantis 35624
Sanofi-Aventis Producer of Bacillus clausii strains O/C, NR, SIN, and T, marketed in Europe, http://www.sanofi-
Asia, and South America as Enterogermina aventis.com
Sensus Frutafit inulin and frutalose fructooligosaccharides (FOS) are http://www.sensus.us
soluble dietary fibers with bifidogenic/prebiotic properties, suitable for
a variety of food systems to enrich fiber, reduce calories, and replace sugars
and fats
Solvay Producer of lactulose (Duphalac) for treatment of constipation http://www.solvay.com
and hepatic encephalopathy
Valio The Lactobacillus rhamnosus GG probiotic is the most researched in the http://www.valio.fi
world and was recently licensed to Dannon for the US yogurt market.
The Gefilus family containing LGG is marketed worldwide
VSL Pharma- VSL#3 is a mixture of 8 strains with 450 billion live bacteria per packet http://www.vsl3.com
ceuticals
Winclove The company sells mixtures of probiotic strains for different indications http://www.winclove.com
Yakult Produces probiotic drinks with L. casei Shirota http://www.yakult.co.jp
LAB indicates lactic acid bacteria.

 The question of safety has been raised with the more probiotic strains. Conventional toxicology and safety
recent use of intestinal isolates of bacteria delivered in evaluation is not sufficient, as a probiotic is meant to
high numbers to severely ill patients. Use of probiotics in survive and/or grow to benefit humans.
ill persons is restricted to the strains and indications with From a scientific perspective, the suitable description of
proven efficacy, as described in section 5. Testing or use a probiotic product as reflected on the label should include:
of probiotics in other disease indications is only accept-  Genus and species identification, with nomenclature con-
able after approval by an independent ethics committee. sistent with current scientifically recognized names.
 On the basis of the prevalence of lactobacilli in fermented  Strain designation.
food, as normal colonizers of the human body, and the  Viable count of each strain at the end of shelf life.
low level of infection attributed to them, the safety of  Recommended storage conditions.
these microbes has been reviewed and their pathogenic  Safety under the conditions of recommended use.
potential is deemed to be quite low.  Recommended dose, which should be based on induc-
 On the basis of the FAO/WHO report (2002), a tion of the claimed physiological effect.
multidisciplinary approach is necessary to examine the  An accurate description of the physiological effect, as far
pathologic, genetic, toxicological, immunologic, gastro- as is allowable by law.
enterological, and microbiological safety aspects of new  Contact information for postmarket surveillance.

472 | www.jcge.com r 2012 Lippincott Williams & Wilkins

J Clin Gastroenterol  Volume 46, Number 6, July 2012 WGO Global Guideline: Probiotics and Prebiotics

PROBIOTICS—THE SCIENCE  Pathogenic microorganisms.

 —Viruses (rotavirus, poliovirus).
Microbial Ecosystem and Mucosal Immunity  —Bacteria (Salmonella, Listeria, Clostridium, etc.).
The information available about the microbial com-  —Parasites (Toxoplasma).
position of the intestinal ecosystem in health and disease is
still limited (Table 6). Mechanisms of Action
 The intestine contains extensive microbiota—100 trillion Prebiotics affect intestinal bacteria by increasing the
bacteria cells that provide an average of 600,000 genes to numbers of beneficial anaerobic bacteria and decreasing the
each human being—located mainly in the colon and population of potentially pathogenic microorganisms (Fig. 3).
comprising hundreds of species of bacteria. Most bacterial Probiotics affect the intestinal ecosystem by stimulating mu-
cells in fecal specimens cannot be grown in culture. cosal immune mechanisms and by stimulating nonimmune
 At the level of species and strains, the microbial diversity mechanisms through antagonism and competition with po-
between individuals is quite remarkable: each individual tential pathogens (Table 7). These phenomena are thought to
harbors his or her own distinctive pattern of bacterial mediate most beneficial effects, including reduction of the
composition, determined partly by the host genotype and incidence and severity of diarrhea, which is one of the most
by initial colonization at birth by vertical transmission. widely recognized uses for probiotics. Probiotics reduce the
 In healthy adults, the fecal composition is stable over risk of colon cancer in animal models, probably because of
time. In the human gut ecosystem, 3 bacterial divisions their role in suppressing the activity of certain bacterial en-
dominate: Bacteroidetes, Firmicutes, and to a lesser zymes that may increase the levels of procarcinogens, but this
extent Actinobacteria. has not been proven in humans.
The normal interaction between gut bacteria and their
host is a symbiotic relationship. An important influence of
upper intestinal bacteria on immune function is suggested CLINICAL APPLICATIONS
by the presence of a large number of organized lymphoid Current insights into the clinical applications for various
structures in the small-intestinal mucosa (Peyer’s patches). probiotics or prebiotics are summarized below (in alphabetical
Their epithelium is specialized for the uptake and sampling order).
of antigens, and they contain lymphoid germinal centers
for induction of adaptive immune responses. In the colon, Cardiovascular Disease
microorganisms can proliferate by fermenting available The use of probiotics/prebiotics for preventative medi-
substrates from diet or endogenous secretions. cine and decreasing risk of cardiovascular disease is still
The intestine is the body’s most important immune unproven.
function–related organ; approximately 60% of the body’s
immune cells are present in the intestinal mucosa. The Colon Cancer
immune system controls immune responses against: The SYNCAN study tested the effect of oligofructose
 Dietary proteins. plus 2 probiotic strains in patients at risk of developing
 —Prevention of food allergies. colonic cancer. The results of the study suggest that a

TABLE 6. Human Intestinal Microbiota. The Gut Microbiota Form a Diverse and Dynamic Ecosystem, Including Bacteria, Archaea, and
Eukarya that Have Adapted to Live on the Intestinal Mucosal Surface or Within the Gut Lumen
Stomach and duodenum
 Harbor very low numbers of microorganisms: <103 bacterial cells/g
of contents
 Mainly lactobacilli and streptococci
 Acid, bile, and pancreatic secretions suppress most ingested
microbes
 Phasic propulsive motor activity impedes stable colonization of the
lumen
Jejunum and ileum
 No. bacteria progressively increase from approximately 104 cells in
the jejunum to 107 cells/g of contents in the distal ileum
Large intestine
 Heavily populated by anaerobes: 1012 cells/g of luminal contents

1, mouth; 2, pharynx; 3, tongue; 4, esophagus; 5, pancreas; 6, stomach; 7, liver; 8, transverse colon; 9, gallbladder; 10, descending colon; 11, duodenum; 12,
jejunum; 13, ascending colon; 14, sigmoid colon; 15, ileum; 16, rectum; 17, anus.

r 2012 Lippincott Williams & Wilkins www.jcge.com | 473

Guarner et al J Clin Gastroenterol  Volume 46, Number 6, July 2012

(boulardii) are useful in reducing the severity and dura-

tion of acute infectious diarrhea in children. The oral
administration of probiotics shortens the duration of
acute diarrheal illness in children by approximately 1 day.
 Several meta-analyses of controlled clinical trials have
been published that show consistent results in systematic
reviews, suggesting that probiotics are safe and effective.
The evidence from studies on viral gastroenteritis is more
convincing than the evidence on bacterial or parasitic in-
fections. Mechanisms of action are strain-specific: there
is evidence for efficacy of some strains of lactobacilli
(eg, L. casei GG and L. reuteri ATCC 55730) and for
S. boulardii. The timing of administration is also of
importance.

Prevention of acute diarrhea:

 In the prevention of adult and childhood diarrhea, there
is only suggestive evidence that Lactobacillus GG,
L. casei DN-114 001, and S. boulardii are effective in
FIGURE 3. The normal microbiota and probiotics interact with some specific settings (Tables 8 and 9).
the host in metabolic activities and immune function and prevent Antibiotic-associated diarrhea:
colonization of opportunistic and pathogenic microorganisms.  In antibiotic-associated diarrhea, there is strong evidence
Journal of Internal Medicine by Blackwell Publishing Ltd. Repro- of efficacy for S. boulardii or L. rhamnosus GG in adults
duced with permission of Blackwell Publishing Ltd. in the format
or children who are receiving antibiotic therapy. One
Journal through Copyright Clearance Center.
study indicated that L. casei DN-114 001 is effective in
hospitalized adult patients for preventing antibiotic-
synbiotic preparation can decrease the expression of bio- associated diarrhea and C. difficile diarrhea.
markers for colorectal cancer. Radiation-induced diarrhea:
Diarrhea  There is inadequate research evidence to be certain
that VSL#3 (L. casei, L. plantarum, L. acidophilus,
Treatment of acute diarrhea:
L. delbrueckii, B. longum, B. breve, B. infantis, and
 It has been confirmed that different probiotic strains
Streptococcus thermophilus) is effective in the treatment
(Tables 8 and 9), including L. reuteri ATCC 55730,
of radiation-induced diarrhea.
L. rhamnosus GG, L. casei DN-114 001, and S. cerevisiae
Eradication of Helicobacter pylori
Several lactobacilli and bifidobacterial strains, as well
TABLE 7. Mechanisms of Probiotic/Host Interaction. Symbiosis as B. clausii, appear to reduce the side effects of antibiotic
Between Microbiota and the Host can be Optimized by therapies and improve patient compliance. Several strains
Pharmacological or Nutritional Interventions in the Gut Microbial were effective in decreasing side effects, but did not have
Ecosystem Using Probiotics or Prebiotics effects on the eradication rate. A recent meta-analysis of 14
Probiotics randomized trials suggests that supplementation of anti-H.
Immunologic pylori antibiotic regimens with certain probiotics may also
benefits  Activate local macrophages to increase be effective in increasing eradication rates and may be
antigen presentation to B lymphocytes considered helpful for patients with eradication failure.
and increase secretory IgA production There is currently insufficient evidence to support the con-
both locally and systemically
 Modulate cytokine profiles
cept that a probiotic alone, without concomitant antibiotic
 Induce hyporesponsiveness to food antigens therapy, would be effective. In summary, there is literature
Nonimmunologic suggesting that certain probiotics may be helpful as
benefits  Digest food and compete for nutrients adjuvant therapy with antibiotics in the eradication of
with pathogens H. pylori infection.
 Alter local pH to create an unfavorable
local environment for pathogens Allergy
 Produce bacteriocins to inhibit pathogens The strongest evidence is for the prevention of atopic
 Scavenge superoxide radicals dermatitis when certain probiotics are administered to preg-
 Stimulate epithelial mucin production
 Enhance intestinal barrier function
nant mothers and newborns up to 6 months of age. How-
 Compete for adhesion with pathogens ever, a recent clinical trial did not confirm these results.
 Modify pathogen-derived toxins With regard to the treatment of allergic disease, a few well-
Prebiotics designed studies have provided evidence that specific pro-
 Metabolic effects: production of short- biotic strains can be effective in the treatment of a subset
chain fatty acids, fat metabolism, of patients with atopic eczema. Little is known about the
absorption of ions (Ca, Fe, Mg) efficacy of probiotics in preventing food allergy.
 Enhancing host immunity (IgA production,
cytokine modulation, etc.) Hepatic Encephalopathy
Ig indicates immunoglobulin. Prebiotics such as lactulose are commonly used for the
prevention and treatment of this complication of cirrhosis.

474 | www.jcge.com r 2012 Lippincott Williams & Wilkins

J Clin Gastroenterol  Volume 46, Number 6, July 2012 WGO Global Guideline: Probiotics and Prebiotics

TABLE 8. Evidence-based Pediatric Indications for Probiotics and Prebiotics in Gastroenterology

Recommended Evidence
Disorder, Action Probiotic Strain/Prebiotic Dose Level References Comments
10 11
Treatment of acute Lactobacillus rhamnosus GG 10 -10 cfu, 1a 1 Meta-analysis of RCTs; ESPGHAN/
infectious diarrhea twice daily ESPID recommendation
Saccharomyces boulardii, strain 200 mg, 3 times 1a 2 Meta-analysis of RCTs; ESPGHAN/
of Saccharomyces cerevisiae daily ESPID recommendation
Indian Dahi containing 1010 cfu of each 2b 3 —
Lactococcus lactis, strain, 2 or 3
Lactococcus lactis cremoris, times per day
and Leuconostoc
mesenteroides cremoris
Prevention of Saccharomyces boulardii, strain 250 mg, twice 1a 4, 5 Meta-analysis of RCTs
antibiotic- of Saccharomyces cerevisiae daily
associated diarrhea
Lactobacillus rhamnosus GG 1010 cfu, once 1b 6, 7 —
or twice daily
Bifidobacterium lactis 107 + 106 cfu/g 1b 8 —
Bb-12 + Streptococcus of formula
thermophilus
Lactobacillus rhamnosus (strains 2 1010 cfu, 1b 9 —
E/N, Oxy, and Pen) twice daily
Prevention of Lactobacillus rhamnosus GG 1010-1011 cfu, 1b 10, 11 —
nosocomial twice daily
diarrhea
Bifidobacterium lactis 108 + 107 cfu/g 1b 12 —
Bb-12 + Streptococcus of formula
thermophilus
Prevention of Lactobacillus casei DN-114 001 1010 cfu, once 1b 13, 14, 15 —
common in fermented milk daily
gastrointestinal
infections acquired
in the community
Bifidobacterium lactis Bb-12 or 107 cfu/g of 1b 16 —
Lactobacillus reuteri ATCC formula
55730 powder
Lactobacillus casei Shirota in 1010 cfu, once 1b 17 —
fermented milk daily
Adjuvant therapy Lactobacillus casei DN-114 001 1010-1012 cfu 1b 18 The probiotic was given together with a
for H. pylori in fermented milk daily, for 14 7-d course of eradication triple
eradication days therapy with omeprazole, amoxicillin,
and clarithromycin
Alleviates some Lactobacillus rhamnosus GG 1010-1011 cfu, 1a 19 Meta-analysis of RCTs
symptoms of twice daily
functional bowel
disorders
Lactobacillus reuteri DSM 108 cfu, twice 1b 20, 21 —
17938 daily
Infantile colic Lactobacillus reuteri DSM 108 cfu/d 1b 22 —
17938
Prevention of Bifidobacterium bifidum NCDO 109 cfu each 1b 23 Meta-analysis of pooled data from
necrotizing 1453, Lactobacillus strain, twice RCTs testing different probiotic
enterocolitis in acidophilus NCDO 1748 daily preparations confirms significant
preterm infants benefits of probiotic supplements in
reducing death and disease in preterm
neonates [26]
Infloran: Lactobacillus 108 cfu each, 1b 24 —
acidophilus + Bifidobacterium twice daily
infantis
Bifidobacterium infantis, 109 cfu each, 1b 25 —
Bifidobacterium bifidum, once daily
Streptococcus thermophilus
Treatment of mildly VSL#3 mixture 4 to 1b 27 —
active ulcerative 9 1011 cfu,
colitis twice daily
RCT indicates Randomized Controlled Trial; ESPGHAN, European Society for Pediatric Gastroenterology, Hepatology and Nutrition; ESPID, European
Society for Paediatric Infectious Diseases.
References for Table 8

r 2012 Lippincott Williams & Wilkins www.jcge.com | 475

Guarner et al J Clin Gastroenterol  Volume 46, Number 6, July 2012

1. Szajewska H, Ruszczyński M, Gieruszczak-Bia"ek D. Lactobacillus GG for treating acute diarrhea in children. A meta-analysis of
randomized controlled trials. Aliment Pharmacol Ther. 2007;25:177–184.
2. Szajewska H, Skorka A, Dylag M. Meta-analysis: Saccharomyces boulardii for treating acute diarrhoea in children. Aliment Pharmacol
Ther. 2007;25:257–264.
3. Agarwal KN, Bhasin SK. Feasibility studies to control acute diarrhoea in children by feeding fermented milk preparations Actimel and
Indian Dahi. Eur J Clin Nutr. 2002;56 (suppl 4):S56–S59.
4. Kotowska M, Albrecht P, Szajewska H. Saccharomyces boulardii in the prevention of antibiotic-associated diarrhoea in children: a
randomized double-blind placebo-controlled trial. Aliment Pharmacol Ther. 2005;21:583–590.
5. Szajewska H, Mrukowicz J. Meta-analysis: non-pathogenic yeast Saccharomyces boulardii in the prevention of antibiotic-associated
diarrhoea. Aliment Pharmacol Ther. 2005;22:365–372.
6. Arvola T, Laiho K, Torkkeli S, et al. Prophylactic Lactobacillus GG reduces antibiotic-associated diarrhoea in children with respiratory
infections: a randomized study. Pediatrics. 1999;104:1–4.
7. Vanderhoof JA, Whitney DB, Antonson DL, et al. Lactobacillus GG in the prevention of antibiotic-associated diarrhoea in children.
J Pediatr. 1999;135:564–568.
8. Correa NB, Peret Filho LA, Penna FJ, et al. A randomized formula controlled trial of Bifidobacterium lactis and Streptococcus
thermophilus for prevention of antibiotic-associated diarrhea in infants. J Clin Gastroenterol. 2005;39:385–89.
9. Ruszczyński M, Radzikowski A, Szajewska H. Clinical trial: effectiveness of Lactobacillus rhamnosus (strains E/N, Oxy and Pen) in the
prevention of antibiotic-associated diarrhoea in children. Aliment Pharmacol Ther. 2008;28:154–161.
10. Szajewska H, Kotowska M, Mrukowicz JZ, et al. Efficacy of Lactobacillus GG in prevention of nosocomial diarrhea in infants.
J Pediatr. 2001;138:361–365.
11. Hojsak I, Abdovińá S, Szajewska H, et al. Lactobacillus GG in the prevention of nosocomial gastrointestinal and respiratory tract
infections. Pediatrics. 2010;125:e1171–e1177.
12. Saavedra JM, Bauman NA, Oung I, et al. Feeding of Bifidobacterium bifidum and Streptococcus thermophilus to infants in hospital for
prevention of diarrhoea and shedding of rotavirus. Lancet. 1994;334:1046–1049.
13. Merenstein D, Murphy M, Fokar A, et al. Use of a fermented dairy probiotic drink containing Lactobacillus casei
(DN-114 001) to decrease the rate of illness in kids: the DRINK study. Eur J Clin Nutr. 2010;64:669–677.
14. Pedone CA, Arnaud CC, Postaire ER, et al. Multicentric study of the effect of milk fermented by Lactobacillus casei on the incidence of
diarrhoea. Int J Clin Pract. 2000;54:568–571.
15. Pedone CA, Bernabeu AO, Postaire ER, et al. The effect of supplementation with milk fermented by Lactobacillus casei (strain DN-114
001) on acute diarrhoea in children attending day care centres. Int J Clin Pract. 1999;53:179–184.
16. Weizman Z, Asli G, Alsheikh A. Effect of a probiotic infant formula on infections in child care centers: comparison of two probiotic
agents. Pediatrics. 2005;115:5–9.
17. Sur D, Manna B, Niyogi SK, et al. Role of probiotic in preventing acute diarrhoea in children: a community-based, randomized,
double-blind placebo-controlled field trial in an urban slum. Epidemiol Infect. 2011;139:919–926.
18. Sykora J, Valeckova K, Amlerova J, et al. Effects of a specially designed fermented milk product containing probiotic Lactobacillus
casei DN-114 001 and the eradication of H. pylori in children: a prospective randomized double-blind study. J Clin Gastroenterol.
2005;39:692–698.
19. Horvath A, Dziechciarz P, Szajewska H. Systematic review and meta-analysis of randomized controlled trials: Lactobacillus rhamnosus
GG for abdominal pain-related functional gastrointestinal disorders in childhood. Aliment Pharmacol Ther. 2011;33:1302–1310.
20. Coccorullo P, Strisciuglio C, Martinelli M, et al. Lactobacillus reuteri (DSM 17938) in infants with functional chronic constipation: a
double-blind, randomized, placebo-controlled study. J Pediatrics. 2010;157:598–602.
21. Romano C, Ferrau’ V, Cavataio F, et al. Lactobacillus reuteri in children with functional abdominal pain (FAP).
J Paediatr Child Health. 2010. [Epub ahead of print]. DOI: 10.1111/j.1440-1754.2010.01797.x.
22. Savino F, Cordisco L, Tarasco V, et al. Lactobacillus reuteri DSM 17938 in infantile colic: a randomized, double-blind, placebo-
controlled trial. Pediatrics. 2010;126:e526–e533.
23. Lin HC, Hsu CH, Chen HL, et al. Oral probiotics prevent necrotizing enterocolitis in very low birth weight preterm infants: a
multicenter, randomized, controlled trial. Pediatrics. 2008;122:693–700.
24. Lin HC, Su BH, Chen AC, et al. Oral probiotics reduce the incidence and severity of necrotizing enterocolitis in very low birth weight
infants. Pediatrics. 2005;115:1–4.
25. Bin-Nun A, Bromiker R, Wilschanski M, et al. Oral probiotics prevent necrotizing enterocolitis in very low birth weight neonates. J
Pediatr. 2005;147:192–196.
26. Deshpande G, Rao S, Patole S, et al. Updated meta-analysis of probiotics for preventing necrotizing enterocolitis in preterm neonates.
Pediatrics. 2010;125:921–930.
27. Miele E, Pascarella F, Giannetti E, et al. Effect of a probiotic preparation (VSL#3) on induction and maintenance of remission in
children with ulcerative colitis. Am J Gastroenterol. 2009;104:437–443.

476 | www.jcge.com r 2012 Lippincott Williams & Wilkins

J Clin Gastroenterol  Volume 46, Number 6, July 2012 WGO Global Guideline: Probiotics and Prebiotics

TABLE 9. Evidence-based Adult Indications for Probiotics and Prebiotics in Gastroenterology

Recommended Evidence
Disorder, Action Probiotic Strain/Prebiotic Dose Level References Comments
8
Treatment of acute Enterococcus faecium LAB SF 68 10 cfu, 3 times 1b 1 —
diarrhea in adults daily
Lactobacillus paracasei B 21060 or 109 cfu, twice 2b 2 —
Lactobacillus rhamnosus GG daily
Saccharomyces boulardii, strain of 109 cfu/capsule 1b 1, 3, 4 —
Saccharomyces cerevisiae of 250 mg, 2-
6 capsules/d
Prevention of Enterococcus faecium LAB SF 68 108 cfu, twice 1b 5 —
antibiotic- daily
associated
diarrhea in adults
Saccharomyces boulardii, strain of 1 g or 1b 5 —
Saccharomyces cerevisiae 4 109 cfu/d
Lactobacillus rhamnosus GG 1010-1011 cfu, 1b 5 —
twice daily
Lactobacillus casei DN-114 001 in 1010 cfu, twice 1b 6 —
fermented milk daily
Bacillus clausii (Enterogermina strains) 2 109 spores, 1b 7 —
3 times daily
Lactobacillus acidophilus 5 1010 cfu, 1b 8, 9 The strains were administered in
CL1285 + Lactobacillus casei LBC80R once or twice capsules or in fermented milk
daily vehicle
Prevention of Lactobacillus casei DN-114 001 in 1010 cfu, twice 1b 6 —
Clostridium fermented milk daily
difficile diarrhea
in adults
Lactobacillus acidophilus + B. bifidum 2 1010 cfu 1b 10 Strain designations not
(Cultech strains) each strain, provided in paper
once daily
Oligofructose 4 g, 3 times per 1b 11 —
day
Lactobacillus rhamnosus 109 cfu each, 2b 12 Probiotic administration
HN001 + Lactobacillus acidophilus once daily reduced fecal counts of
NCFM Clostridium difficile in elderly
patients without diarrhea
Lactobacillus acidophilus 5 109 cfu, 1b 9 —
CL1285 + Lactobacillus casei LBC80R once or twice
daily
Saccharomyces boulardii, strain of 2-3 109 for 1b 13, 14 —
Saccharomyces cerevisiae 28 d,
followed for
another 4 wk
Coadjuvant Lactobacillus rhamnosus GG 6 109 cfu, 1b 15 —
therapy for twice daily
Helicobacter
pylori eradication
in adults
Bacillus clausii (Enterogermina strains)2 109 spores, 1b 15 —
3 times daily
Saccharomyces boulardii, strain of 500 mg-1 g or 2- 1b 15-19 —
Saccharomyces cerevisiae 4 109 cfu/d
Kefir 250 mL, twice 2b 20 Improves eradication rates
daily (78% vs 50%)
Lactobacillus reuteri ATCC 55730 108 cfu/d 1b 21
Reduces symptoms Yogurt with live cultures of Lactobacillus At least 108 cfu 1a 22 Systematic review of RCTs
associated with delbrueckii subsp. bulgaricus and of each strain
lactose Streptococcus thermophilus per gram of
maldigestion product
Alleviates some Bifidobacterium infantis 35624 108 cfu, once 1b 23, 24, 25 —
symptoms of daily
irritable bowel
syndrome
Bifidobacterium animalis DN-173 010 in 1010 cfu, twice 1b 26, 27, 25 —
fermented milk daily
Lactobacillus acidophilus SDC 2012, 2013 1010 cfu/d 2b 28, 25 —
Lactobacillus rhamnosus GG, 1010 cfu, once 1b 29, 30, 25 —
Lactobacillus rhamnosus LC705, daily

r 2012 Lippincott Williams & Wilkins www.jcge.com | 477

Guarner et al J Clin Gastroenterol  Volume 46, Number 6, July 2012

TABLE 9. (continued)
Recommended Evidence
Disorder, Action Probiotic Strain/Prebiotic Dose Level References Comments
Bifidobacterium breve Bb99 and
Propionibacterium freudenreichii species
shermanii
Bifidobacterium longum 101 (29%), 1010 cfu, once 1b 31, 25 —
Lactobacillus acidophilus 102 (29%), daily
Lactococcus lactis 103 (29%), and
Streptococcus thermophilus 104 (13%)
Short-chain fructooligosaccharides 5 g/d 2b 32 —
Galactooligosaccharides 3.5 g/d 2b 33 —
Bacillus coagulans GBI-30, 6086 2 109 cfu, 2b 34 —
once daily
Maintenance of Escherichia coli Nissle 1917 5 1010 viable 1b 35 —
remission in bacteria,
ulcerative colitis twice daily
Treatment of mildly VSL#3 mixture of 8 strains (1 2-9 1011 cfu, 1b 36, 37, 43 —
active ulcerative Streptococcus thermophilus, 4 twice daily
colitis or Lactobacillus, 3 Bifidobacterium)
pouchitis
Prevention and VSL#3 mixture of 8 strains (1 2-4.5 1011 cfu, 1b 38 —
maintenance of Streptococcus thermophilus, 4 twice daily
remission in Lactobacillus, 3 Bifidobacterium)
pouchitis
Treatment of Lactulose 20-40 g/d 1a 39 Review of cohort studies
constipation
Oligofructose > 20 g/d 2a 40 Review of cohort studies
Treatment of Lactulose 45-90 g/d 1a 41 Systematic review of RCTs
hepatic
encephalopathy
Prevention of Lactobacillus casei Shirota in 1010 cfu, once 1b 42 —
common fermented milk daily
infections in
athletes
LAB indicates lactic acid bacteria.
References for Table 9

1. Allen SJ, Martinez EG, Gregorio GV, et al. Probiotics for treating acute infectious diarrhoea. Cochrane Database Syst Rev.
2010:CD003048.
2. Grossi E, Buresta R, Abbiati R, et al. Pro-DIA study group. Clinical trial on the efficacy of a new symbiotic formulation, Flortec, in
patients with acute diarrhea: a multicenter, randomized study in primary care. J Clin Gastroenterol. 2010;44 (suppl 1):S35–S41.
3. Hochter W, Chase D, Hagenhoff G. Saccharomyces boulardii in acute adult diarrhea: efficacy and tolerability of treatment. Munch Med
Wochenschr. 1990;132:188–192.
4. Mansour-Ghanaei F, Dehbashi N, Yazdanparast K, et al. Efficacy of Saccharomyces boulardii with antibiotics in acute amoebiasis.
World J Gastroenterol. 2003;9:1832–1833.
5. Sazawal S, Hiremath G, Dhingra U, et al. Efficacy of probiotics in prevention of acute diarrhoea: a meta-analysis of masked,
randomised, placebo-controlled trials. Lancet Infect Dis. 2006;6:374–382.
6. Hickson M, D’Souza AL, Muthu N, et al. Use of probiotic Lactobacillus preparation to prevent diarrhoea associated with antibiotics:
randomised double blind placebo controlled trial. BMJ. 2007;335:80.
7. Nista EC, Candelli M, Cremonini F, et al. Bacillus clausii therapy to reduce side-effects of anti-Helicobacter pylori treatment:
randomized, double-blind, placebo controlled trial. Aliment Pharmacol Ther. 2004;20:1181–1188.
8. Beausoleil M, Fortier N, Guénette S, et al. Effect of a fermented milk combining Lactobacillus acidophilus Cl1285 and Lactobacillus
casei in the prevention of antibiotic-associated diarrhea: a randomized, double-blind, placebo-controlled trial. Can J Gastroenterol.
2007;21:732–736.
9. Gao XW, Mubasher M, Fang CY, et al. Dose-response efficacy of a proprietary probiotic formula of Lactobacillus acidophilus CL1285
and Lactobacillus casei LBC80R for antibiotic-associated diarrhea and Clostridium difficile-associated diarrhea prophylaxis in adult
patients. Am J Gastroenterol. 2010;105:1636–1641.
10. Plummer S, Weaver MA, Harris JC, et al. Clostridium difficile pilot study: effects of probiotic supplementation on the incidence of
Clostridium difficile diarrhoea. Int Microbiol. 2004;7:59–62.
11. Lewis S, Burmeister S, Brazier J. Effect of the prebiotic oligofructose on relapse of Clostridium difficile-associated diarrhea: a
randomized, controlled study. Clin Gastroenterol Hepatol. 2005;3:442–448.
12. Lahtinen SJ, Forssten S, Aakko J, et al. Probiotic cheese containing Lactobacillus rhamnosus HN001 and Lactobacillus acidophilus
NCFM(s) modifies subpopulations of fecal lactobacilli and Clostridium difficile in the elderly. Age (Dordr). 2012;34:133–143.
13. McFarland LV, Surawicz CM, Greenberg RN, et al. A randomized placebo-controlled trial of Saccharomyces boulardii in combination
with standard antibiotics for Clostridium difficile disease. JAMA. 1994;271:1913–1918.
14. Surawicz CM, McFarland LV, Greenberg RN, et al. The search for a better treatment for recurrent Clostridium difficile disease: use of
high-dose vancomycin combined with Saccharomyces boulardii. Clin Infect Dis. 2000;31:1012–1017.

478 | www.jcge.com r 2012 Lippincott Williams & Wilkins

J Clin Gastroenterol  Volume 46, Number 6, July 2012 WGO Global Guideline: Probiotics and Prebiotics

15. Tong JL, Ran ZH, Shen J, et al. Meta-analysis: the effect of supplementation with probiotics on eradication rates and adverse events
during Helicobacter pylori eradication therapy. Aliment Pharmacol Ther. 2007;25:155–68.
16. Cindoruk M, Erkan G, Karakan T, et al. Efficacy and safety of Saccharomyces boulardii in the 14-day triple anti-Helicobacter pylori
therapy: a prospective randomized placebo-controlled double-blind study. Helicobacter. 2007;12:309–316.
17. Cremonini F, Di Caro S, Covino M, et al. Effect of different probiotic preparations on anti-Helicobacter pylori therapy-related side
effects: a parallel group, triple blind, placebo-controlled study. Am J Gastroenterol. 2002;97:2744–2749.
18. Duman DG, Bor S, Ozütemiz O, et al. Efficacy and safety of Saccharomyces boulardii in prevention of antibiotic-associated diarrhoea
due to Helicobacter pylori eradication. Eur J Gastroenterol Hepatol. 2005;17:1357–1361.
19. Song MJ, Park DI, Park JH, et al. The effect of probiotics and mucoprotective agents on PPI-based triple therapy for eradication of
Helicobacter pylori. Helicobacter. 2010;15:206–213.
20. Bekar O, Yilmaz Y, Gulten M. Kefir Improves the efficacy and tolerability of triple therapy in eradicating Helicobacter pylori. J Med
Food. 2011;14:344–347.
21. Lionetti E, Miniello VL, Castellaneta SP, et al. Lactobacillus reuteri therapy to reduce side-effects during anti-Helicobacter pylori
treatment in children: a randomised placebo controlled trial. Aliment Pharmacol Ther. 2006;24:1461–1468.
22. EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA). Scientific opinion on the substantiation of health claims related to
live yoghurt cultures and improved lactose digestion (ID 1143, 2976) pursuant to Article 13(1) of Regulation (EC) No 1924/2006. EFSA
J. 2010;8:1763.
23. O’Mahony L, McCarthy J, Kelly P, et al. Lactobacillus and Bifidobacterium in irritable bowel syndrome: symptom responses and
relationship to cytokine profiles. Gastroenterology. 2005;128:541–551.
24. Whorwell PJ, Altringer L, Morel J, et al. Efficacy of an encapsulated probiotic Bifidobacterium infantis 35624 in women with irritable
bowel syndrome. Am J Gastroenterol. 2006;101:1581–1590.
25. Moayyedi P, Ford AC, Talley NJ, et al. The efficacy of probiotics in the treatment of irritable bowel syndrome: a systematic review.
Gut. 2010;59:325–332.
26. Guyonnet D, Chassany O, Ducrotte P, et al. Effect of a fermented milk containing Bifidobacterium animalis DN-173 010 on the health-
related quality of life and symptoms in irritable bowel syndrome in adults in primary care: a multicentre, randomized, double-blind,
controlled trial. Aliment Pharmacol Ther. 2007;26:475–486.
27. Agrawal A, Houghton LA, Morris J, et al. Clinical trial: the effects of a fermented milk product containing Bifidobacterium lactis DN-
173 010 on abdominal distension and gastrointestinal transit in irritable bowel syndrome with constipation. Aliment Pharmacol Ther.
2009;29:104–114.
28. Sinn DH, Song JH, Kim HJ, et al. Therapeutic effect of Lactobacillus acidophilus-SDC 2012, 2013 in patients with irritable bowel
syndrome. Dig Dis Sci. 2008;53:2714–2718.
29. Kajander K, Hatakka K, Poussa T, et al. A probiotic mixture alleviates symptoms in irritable bowel syndrome patients: a controlled 6-
month intervention. Aliment Pharmacol Ther. 2005;22:387–394.
30. Kajander K, Myllyluoma E, Rajilic-Stojanovics M, et al. Clinical trial: multispecies probiotic supplementation alleviates the symptoms
of irritable bowel syndrome and stabilizes intestinal microbiota. Aliment Pharmacol Ther. 2008;27:48–57.
31. Drouault-Holowacz S, Bieuvelet S, Burckel A, et al. A double blind randomized controlled trial of a probiotic combination in 100
patients with irritable bowel syndrome. Gastroenterol Clin Biol. 2008;32:147–152.
32. Paineau D, Payen F, Panserieu S, et al. The effects of regular consumption of short-chain fructo-oligosaccharides on digestive comfort
of subjects with minor functional bowel disorders. Br J Nutr. 2008;99:311–318.
33. Silk DBA, Davis A, Vulevic J, et al. Clinical trial: the effects of a trans-galactooligosaccharide prebiotic on faecal microbiota and
symptoms in irritable bowel syndrome. Aliment Pharmacol Ther. 2009;29:508–518.
34. Dolin BJ. Effect of a proprietary Bacillus coagulans on symptoms of diarrhea-predominant irritable bowel syndrome. Methods Find Exp
Clin Pharmacol. 2009;31:655–659.
35. Kruis W, Fric P, Pokrotnieks J, et al. Maintaining remission of ulcerative colitis with the probiotic Escherichia coli Nissle 1917 is as
effective as with standard mesalazine. Gut. 2004;53:1617–1623.
36. Tursi A, Brandimarte G, Papa A, et al. Treatment of relapsing mild-to-moderate ulcerative colitis with the probiotic VSL#3 as
adjunctive to a standard pharmaceutical treatment: a double-blind, randomized, placebo-controlled study. Am J Gastroenterol.
2010;105:2218–2227.
37. Gionchetti P, Rizzello F, Morselli C, et al. High-dose probiotics for the treatment of active pouchitis. Dis Colon Rectum.
2007;50:2075–2082.
38. Gionchetti P, Rizzello F, Helwig U, et al. Prophylaxis of pouchitis onset with probiotic therapy: a double-blind, placebo-controlled
trial. Gastroenterology. 2003;124:1202–1209.
39. Schumann C. Medical, nutritional and technological properties of lactulose. An update. Eur J Nutr. 2002;41 (suppl 1):I17–I25.
40. Nyman M. Fermentation and bulking capacity of indigestible carbohydrates: the case of inulin and oligofructose. Br J Nutr. 2002;87
(suppl 2):S163–S168.
41. Shukla S, Shukla A, Mehboob S, et al. Meta-analysis: the effects of gut flora modulation using prebiotics, probiotics and synbiotics on
minimal hepatic encephalopathy. Aliment Pharmacol Ther. 2011;33:662–671.
42. Gleeson M, Bishop NC, Oliveira M, et al. Daily probiotic’s (Lactobacillus casei Shirota) reduction of infection incidence in athletes. Int
J Sport Nutr Exerc Metab. 2011;21:55–64.
43. Sood A, Midha V, Makharia GK, et al. The probiotic preparation, VSL#3 induces remission in patients with mild-to-moderately active
ulcerative colitis. Clin Gastroenterol Hepatol. 2009;7:1202–1209.

r 2012 Lippincott Williams & Wilkins www.jcge.com | 479

Guarner et al J Clin Gastroenterol  Volume 46, Number 6, July 2012

Minimal hepatic encephalopathy was reversed in 50% of Nonalcoholic Fatty Liver Disease
patients treated with a synbiotic preparation (4 probiotic The usefulness of probiotics as a treatment option has
strains and 4 fermentable fibers, including inulin and not been sufficiently confirmed through randomized clinical
resistant starch) for 30 days. trials.
Prevention of Systemic Infections
Immune Response There is insufficient evidence to support the use of
There is suggestive evidence that several probiotic probiotics and synbiotics in critically ill adult patients in
strains and the prebiotic oligofructose are useful in boosting intensive care units.
the immune response. Indirect evidence has been obtained in
studies aimed at preventing acute infectious disease (noso-
PROBIOTICS, PREBIOTICS, AND EVIDENCE—THE
comial diarrhea in children, influenza episodes in winter)
and studies that tested antibody responses to vaccines. GLOBAL PICTURE
Tables 8 and 9 summarize a number of clinical conditions
for which there is evidence, from at least 1 well-designed and
Inflammatory Bowel Disease properly powered clinical trial, that oral administration of a
Pouchitis: specific probiotic strain or a prebiotic is effective and beneficial
 There is good evidence for the usefulness of probiotics in for a healthy or therapeutic outcome. The list may not be
preventing an initial attack of pouchitis (VSL#3), and in complete, as the flow of new published studies has been con-
preventing further relapse of pouchitis after the induc- tinuous during the past few years. The level of evidence may
tion of remission with antibiotics. Probiotics can be vary between the different indications. Recommended doses
recommended to patients with pouchitis of mild activity, are those shown to be useful in the trials. The order of the
or as maintenance therapy for those in remission. products listed is random. Currently, there is insufficient
Ulcerative colitis: evidence from comparative studies to rank the products with
 The probiotic E. coli Nissle strain may be equivalent to proven efficacy.
mesalazine in maintaining remission of ulcerative colitis.
The probiotic mixture VSL#3 has shown efficacy to AUTOMATIC SEARCHES AND FURTHER READING
induce and maintain remission in children and adults
with mild to moderate ulcerative colitis. Automatic PubMed Searches
Crohn’s disease:
 Studies of probiotics in Crohn’s disease have been disap-
pointing, and the Cochrane systematic review concluded
that there is no evidence to suggest that probiotics are Precise literature search for
beneficial for maintenance of remission in Crohn’s probiotics research published
disease. in the last 6 months in the top
clinical journals.
Click on the WGO logo to
IBS begin the search.
Several studies have demonstrated significant ther-
apeutic gains with probiotics in comparison with placebo.
A reduction in abdominal bloating and flatulence as a result
of probiotic treatments is a consistent finding in published
studies; some strains may ameliorate pain and provide
global relief (B. infantis 35624) in addition. L. reuteri may Sensitive literature search for
improve colicky symptoms within 1 week of treatment, as probiotics research published
shown in a recent trial with 90 breastfed babies with in- in the last 3 years in all
fantile colic. In summary, there is literature suggesting that journals.
certain probiotics may alleviate symptoms in persons with Click on the WGO logo to
functional abdominal pain. begin the search.

Lactose Malabsorption
S. thermophilus and L. delbrueckii subsp. bulgaricus
improve lactose digestion and reduce symptoms related to References and Further Reading
lactose intolerance. This was confirmed in a number of 1. Allen SJ, Martinez EG, Gregorio GV, et al. Probiotics for
controlled studies with individuals consuming yogurt with treating acute infectious diarrhoea. Cochrane Database Syst
live cultures. Rev. 2010. doi: 10.1002/14651858.CD003048.pub3 http://doi.
wiley.com/10.1002/14651858.CD003048.pub3. Accessed May 12,
2012.
Necrotizing Enterocolitis
2. Deshpande G, Rao S, Patole S, et al. Updated meta-analysis of
Clinical trials have shown that probiotic supple- probiotics for preventing necrotizing enterocolitis in preterm
mentation reduces the risk of necrotizing enterocolitis in neonates. Pediatrics. 2010;125:921–930.
preterm neonates. Systematic reviews of randomized con- 3. Floch MH, Madsen KK, Jenkins DJ, et al. Recommendations
trolled trials have also shown a reduced risk of death in for probiotic use. J Clin Gastroenterol. 2006;40:275–278.
probiotic-treated groups. The numbers-needed-to-treat to 4. Gibson GR, Roberfroid MB. Dietary modulation of the
prevent 1 death from all causes by treatment with pro- human colonic microbiota: introducing the concept of pre-
biotics is 20. biotics. J Nutr. 1995;125:1401–1412.

480 | www.jcge.com r 2012 Lippincott Williams & Wilkins

J Clin Gastroenterol  Volume 46, Number 6, July 2012 WGO Global Guideline: Probiotics and Prebiotics

5. Hickson M, D’Souza AL, Muthu N, et al. Use of probiotic 20. Szajewska H, Skórka A, Ruszczyński M, et al. Meta-analysis:
Lactobacillus preparation to prevent diarrhoea associated with Lactobacillus GG for treating acute diarrhoea in children.
antibiotics: randomized double blind placebo controlled trial. Aliment Pharmacol Ther. 2007;25:871–881.
BMJ. 2007;335:80–83. 21. Tong JL, Ran ZH, Shen J, et al. Meta-analysis: the effect of
6. Johnston BC, Supina AL, Ospina M, et al. Probiotics for the supplementation with probiotics on eradication rates and
prevention of pediatric antibiotic-associated diarrhea. Co- adverse events during Helicobacter pylori eradication therapy.
chrane Database Syst Rev. 2007:CD004827. Aliment Pharmacol Ther. 2007;25:155–168.
7. Lemberg DA, Ooi CY, Day AS. Probiotics in paediatric 22. Van Loo JV, Gibson GR, Probert HM, et al. Dietary
gastrointestinal diseases. J Paediatr Child Health. 2007; modulation of the human colonic microbiota: updating the
43:331–336. concept of prebiotics. Nutr Res Rev. 2004;17:259–275.
8. Lenoir-Wijnkoop I, Sanders ME, Cabana MD, et al. Probiotic 23. Yan F, Polk DB. Probiotics: progress toward novel therapies
and prebiotic influence beyond the intestinal tract. Nutr Rev. for intestinal diseases. Curr Opin Gastroenterol. 2010;26:95–101.
2007;65:469–489.
9. Lirussi F, Mastropasqua E, Orando S, et al. Probiotics for USEFUL WEB SITES
non-alcoholic fatty liver disease and/or steatohepatitis. Co-  http://www.isapp.net
chrane Database Syst Rev. 2007:CD005165. ISAP: The International Scientific Association for Probiotics
10. Mallon P, McKay D, Kirk S, et al. Probiotics for induction of and Prebiotics
remission in ulcerative colitis. Cochrane Database Syst Rev. The organization aims to engender and disseminate informa-
2007:CD005573. tion on high-quality, multidisciplinary, scientific investigations
11. Meurman JH, Stamatova I. Probiotics: contributions to oral in the fields of probiotics and prebiotics, and to advance the
health. Oral Dis. 2007;13:443–451. development of scientifically substantiated, health-promoting
12. O’Mahony LJ, McCarthy J, Kelly P, et al. Lactobacillus and probiotic and prebiotic products worldwide.
Bifidobacterium in irritable bowel syndrome: symptom re-  http://www.usprobiotics.org
sponses and relationship to cytokine profiles. Gastroenterol- Webcast: Probiotics: Applications in Gastrointestinal Health
ogy. 2005;128:541–551. and Disease
13. Osborn DA, Sinn JK. Probiotics in infants for prevention of Presented in conjunction with the American College of
allergic disease and food hypersensitivity. Cochrane Database Gastroenterology’s 72nd Annual Scientific Meeting, Autumn
Syst Rev. 2007:CD006475. 2007.
14. Quigley EM. Therapies aimed at the gut microbiota and  http://www.fao.org/ag/agn/agns/micro_probiotics_en.asp
inflammation: antibiotics, prebiotics, probiotics, synbiotics, The FAO food safety and quality site for probiotics.
anti-inflammatory therapies. Gastroenterol Clin North Am.  http://www.nestlefoundation.org/
2011;40:207–222.  http://www.dannonprobioticscenter.com/index.asp
15. Qin J, Li R, Raes J, et al. A human gut microbial gene A Danone company—one of the leading research organiza-
catalogue established by metagenomic sequencing. Nature. tions in the field of probiotics.
2010;464:59–65.
16. Sazawal SG, Hiremath U, Dhingra P, et al. Efficacy of QUERIES AND FEEDBACK
probiotics in prevention of acute diarrhoea: a meta-analysis of The Guidelines Committee welcomes any comments
masked randomised, placebo-controlled trials. Lancet Infect and queries that readers may have. Do you feel we have
Dis. 2006;6:374–382.
neglected some aspects of the topic? Do you think that
17. Shanahan F. Probiotics in perspective. Gastroenterology. 2010; some procedures are associated with extra risk? Tell us
139:1808–1812.
about your own experience. You are welcome to e-mail the
18. Szajewska H, Ruszczyński M, Radzikowski A. Probiotics in
the prevention of antibiotic-associated diarrhea in children: a address below and let us know your views.
meta-analysis of randomized controlled trials. J Pediatr.
2006;149:367–372.
19. Szajewska H, Skórka A, Dylag M. Meta-analysis: Saccha- guidelines@worldgastroenterology
romyces boulardii for treating acute diarrhoea in children.
Aliment Pharmacol Ther. 2007;25:257–264.

r 2012 Lippincott Williams & Wilkins www.jcge.com | 481

View publication stats