RESEARCH
Perspectives in Practice
Probiotics and Prebiotics in Dietetics Practice
LINDA C. DOUGLAS, PhD, RD; MARY E. SANDERS, PhD
ABSTRACT
Probiotics and prebiotics share a unique role in human
nutrition, largely centering on manipulation of popula-
tions or activities of the bacteria that colonize our bodies.
Benefits of regular consumption of probiotics or prebiotics
include enhanced immune function, improved colonic in-
tegrity, decreased incidence and duration of intestinal
infections, down-regulated allergic response, and im-
proved digestion and elimination. Research has shown
that probiotics and prebiotics may be useful in achieving
these and other positive effects, provided that proper
strain, product selection, and dosing guidelines of com-
mercial products are followed. There is a need to consol-
idate the basic and applied research on probiotics and
prebiotics into useful tools for food and nutrition profes-
sionals. Information on probiotic species, applications for
specific strains, dosages and forms, safety, and shelf life
is not sufficiently summarized to allow practical and
consistent recommendations to be made by most food
and nutrition professionals. In addition, prebiotic fibers—
although providing nutraceutical and nutritional value—
are a group of diverse carbohydrate ingredients that are
poorly understood in regard to their origin, fermentation
profiles, and dosages required for health effects. The sci-
ence and practice-based guidelines presented here will
enhance clinician and client understanding of probiotics
and prebiotics, with the aim of improving appropriate
recommendation and informed use of these emerging di-
etary ingredients and the products containing them.
J Am Diet Assoc. 2008;108:510-521.
PROBIOTICS
The Probiotic Concept
A
common perception is that microbes are bad—an
idea fueled by an abundance of information about
pathogenic bacteria, yeast, and viruses and their
associated morbidity and mortality. But a growing body
of research is documenting the diverse ways that certain
other microbes, called probiotics, can contribute to hu-
man health. Probiotics are live microorganisms that
L. C. Douglas is a food science and nutrition consultant
in Lone Tree, CO. M. E. Sanders is a probiotic microbi-
ologist, consultant, and owner of Dairy & Food Culture
Technologies, Centennial, CO.
Address correspondence to: Linda C. Douglas, PhD,
RD. E-mail: lacdouglas@comcast.net
Copyright © 2008 by the American Dietetic
Association.
0002-8223/08/10803-0014$34.00/0
doi: 10.1016/j.jada.2007.12.009
510 Journal of the AMERICAN DIETETIC ASSOCIATION
when administered in adequate amounts confer a health
benefit on the host (1).
The concept of probiotics emerged from observations
early in the 19th century by Russian immunologist Elie
Metchnikoff, who hypothesized that the long and healthy
lives of Bulgarian peasants were rooted in their consump-
tion of fermented milks containing beneficial Lactobacil-
lus, and the positive influence of these microbes on colonic
health (2). More than 100 years later, it is apparent that
microbes have an important influence on immune devel-
opment and resistance to infection (3); that microbes are
not static colonizers of our bodies, but are dynamic, sym-
biotic coresidents (4); that environmental exposure and
consumption of microbes is much reduced compared to
that of our ancient ancestors (5); and that this low expo-
sure is hypothesized to contribute to health problems,
including the rise in inflammatory and allergic disorders
in modern societies (6). The probiotic concept states that
consuming the right types of microbes can support the
important roles that colonizing microbes play in human
health. The scientific support for health effects and mech-
anisms of effects of probiotics is still emerging. This is an
evidence-based discussion of probiotics and the consider-
ations clinicians must assess when developing recom-
mendations for probiotics in practice.
Although there is an accepted scientific definition,
there is no legal definition for the term “probiotic.” There-
fore this term is used commercially even when the mini-
mum scientific criteria for probiotics (Figure 1) are not
met. Probiotic is not a synonym for native beneficial bac-
teria, although they may be isolated from this source. The
term “probiotic,” by definition, can never be used to de-
scribe products comprised primarily of dead bacteria,
even though in some cases dead bacteria or bacterial cell
products have been shown to have physiologic effects (7).
Another term should be used to describe such substances.
Different microbes have been studied as probiotics.
Most commonly in products in the United States are
strains of different species of Lactobacillus or Bifidobac-
terium, but the yeast Saccharomyces cerevisiae (boular-
dii) is also used. Some other bacteria, including strains of
Enterococcus, Bacillus, and Escherichia, are also used but
these microbes are typically not found as ingredients in
foods, only supplements.
Products
In the absence of a legal definition of the term “probiotic,”
consumers and health care professionals are at a disad-
vantage in choosing among the broad assortment of sup-
plements and now increasing number of food products
claiming to be probiotic. Rare are the products on the
market that provide objective assurances through inde-
pendent, third-party analysis that they are what they
© 2008 by the American Dietetic Association
Definitions
Colonocytes: Organ cells comprising the colon.
Colony-forming units (cfu): This is the measure of the count of bacteria when assayed on solid growth media,
or an agar plate. The bacterial suspension is diluted serially so that when a small amount is spread on the surface
of an agar plate, between 30 and 300 microbes will be spread out on the surface of the plate. The plate is incubated
until each bacterial cell forms a colony visible with the naked eye. After figuring the dilution factor, this assay results
in a count (cfu) per milliliter or gram of test product.
Dietary fiber: Currently, this definition consists of nondigestible carbohydrates and lignin that are intrinsic and
intact in plants.
Dietary supplement: Defined in US food law by the 1994 Dietary Supplement Health and Education Act, a
dietary supplement is a product that is intended to supplement the diet, must be ingested, commonly in the form of
pill, capsule, tablet, powder or liquid, and is not represented for use as a conventional food or as the sole item of a
meal or diet. Furthermore, a dietary supplement must be labeled as a “dietary supplement.”
Fermentation: A process in which an agent, such as a microorganism, transforms organic matter into other
products.
Fructooligosaccharides: Fructooligosaccharides are glucose or fructose-terminated polymers of fructose natu-
rally occurring in a variety of plants. Most of the commercially available fructooligosaccharides are manufactured
from sucrose and are considered functional fiber. Despite differences in chemical structure, fructooligosaccharides
are frequently labeled as oligofructose.
Functional Fiber: This is a category consisting of isolated, nondigestible carbohydrates that have beneficial
physiological effects in humans. This category of fiber includes inulin, oligofructose, short-chain fructooligosaccha-
rides, and resistant starch.
Health claim. Defined in the United States as any claim that expressly or by implication characterizes the
relationship of a dietary substance to the reduction of risk of a disease or health-related condition. Pre-approval must
be obtained prior to use on food or dietary supplement labels.
Inulin and Oligofructose: Inulin and oligofructose are carbohydrates naturally occurring in a variety of plants.
Most of the commercially available inulin and oligofructose is either synthesized from sucrose or extracted and
purified from chicory roots. Oligofructose is also formed by partial hydrolysis of inulin. Both are classified as
functional fibers.
Live cultures: Live cultures are microbes associated with foods as food fermentation agents, or starter cultures.
Many probiotics would be considered to be “live cultures.” But some probiotics would not typically be added to foods
(such as certain strains of Escherichia coli used as probiotics), and as such would not typically be referred to as a “live
culture.” Therefore, the term “probiotic” cannot be considered a synonym of “live cultures.”
Medical food: A food administered under the supervision of a physician and intended for the specific dietary
management of a disease for which distinctive nutritional requirements are established.
Microbiota: Term used to describe the multitude of microorganisms harboring a specific ecological niche. The
term “microflora” is commonly used instead in medical literature, but this is a less accurate term scientifically since
most microbes are not plants (ie, flora).
Prebiotic: A nondigestible food ingredient that beneficially affects the host by selectively stimulating the growth
and/or activity of one or a limited number of bacteria in the colon.
Probiotic: Live microorganism which when administered in adequate amounts confer a health benefit on the host.
Resistant Starch: Resistant starch is naturally occurring, but can also be produced by the modification of starch
during the processing of foods through the cooking and cooling or extrusion of starchy foods. It is also manufactured
for use in the food industry as a functional fiber.
Starter Culture. Live microbes used to transform raw foods into fermented foods. Frequently these microbes are
members of a group of bacteria called “lactic acid bacteria” which include species of Lactobacillus and Lactococcus,
and Streptococcus thermophilus. The starter cultures used to make yogurt are Lactobacillus bulgaricus and
Streptococcus thermophilus.
Structure/function claim: Also known as “statement of nutritional support,” this type of claim relates to how a
substance affects the normal structure and functioning of the human body. Used on conventional foods and dietary
supplements, no pre-approval by the Food and Drug Administration (FDA) of this type of claim is needed, although
the FDA must be notified if used on a dietary supplement. The FDA requires that structure/function claims are
truthful and not misleading.
Synbiotic: A food or supplement product containing both probiotics and prebiotics as defined above. The name
derives from a proposed synergism between probiotics and prebiotics
Total Fiber: The sum of dietary fiber and functional fiber.
Trophic: Of or relating to nutrition.
Viscosity and Fermentability: These are terms that replaced the words soluble and insoluble as fiber descrip-
tions in 2005, as determined by the Food and Nutrition Board of the National Institutes of Medicine.

March 2008 ● Journal of the AMERICAN DIETETIC ASSOCIATION 511


Purified strain of the candidate microbe (usually bacterium or
yeast)
Identified to the strain level using biochemical and genetic
techniques
Shown in human studies to improve some parameter of human
health
Safe for target consumers
Figure 1. Minimum criteria to be considered a probiotic for use by
human beings (9). Note that attributes such as adherence to intestinal
cells and being derived from human origin are not requirements (8).
claim to be. Therefore, product labels and Web sites are
the main source of information on what types of probiotic
microbes products contain, what levels are contained in
the product through the end of shelf life, whether the
product has been shown in human studies to provide any
health benefits, and whether the claims of benefits made
on the product have been substantiated.
Not all products on the market claiming to be probiotic
meet the minimum criteria established for a probiotic (8).
Unfortunately, cavalier use of the term “probiotic” on
labeling or promotional material, when a product does
not actually contain adequate levels of a scientifically
documented strain, threatens consumer confidence in all
probiotic-containing products.
Figure 2 lists some commercially available probiotic-
containing products in the United States and the pub-
lished benefits associated with the strains in these prod-
ucts. Figure 2 does not list all of the dozens of products
that are commercially available and sold as probiotics,
but focuses on foods and supplements that are clearly tied
to human studies documenting efficacy. Other products
may be supported by product-specific research, but these
would not be included in Figure 2 unless the studies are
published, and unless studies stipulate strain designa-
tions and doses that can be clearly associated with strains
contained in the products. This information should be
available from product manufacturers. Note that some
indications listed in Figure 2 would be considered drug
applications in the United States. None of the products
listed in Figure 2 are marketed as drugs and, therefore,
are precluded from listing these indications on labels or
in other forms of consumer communication.
Health Benefits of Probiotics
Many reviews are available that provide a comprehensive
view of the numerous types of health effects and mecha-
nisms of action that have been discovered for probiotics
and it is beyond the scope of this review to explore
these in detail (9-14). The Web site www.usprobiotics.
org also provides accurate, useful information on the
subject.
Although there is a long list of different health effects
attributable to probiotics, it must be remembered that
these effects may have been observed for only one or a
limited number of strains, and other strains of even the
same species cannot be presumed to demonstrate the
same effect. The following effects of probiotics have been
512 March 2008 Volume 108 Number 3
reported in the scientific literature: regulation of immune
function (including both enhanced immune response to
pathogens and down-regulated autoimmune and inflam-
matory responses), prolongation of remission in patients
with pouchitis, shortening the duration of infectious di-
arrhea in infants, enhanced gastrointestinal tolerance to
antibiotic therapy, and control of symptoms associated
with lactose intolerance. Health targets with promising,
but emerging, human evidence include reduction of inci-
dence and improvement of symptoms of some allergic
diseases, improved therapeutic outcome for women being
treated for bacterial vaginosis, improved symptoms
among those with irritable bowel syndrome, decreased
incidence of dental caries, reduced severity of symptoms
or incidence of respiratory infections, reduction of Clos-
tridium difficile toxin in subjects taking antibiotics, and
reduced absences or illness in workplace or day-care cen-
ter settings (15-34).
It is also worth noting well-conducted studies that did
not show positive effects of probiotics, including studies
on antibiotic-associated diarrhea, prevention of surgical
infections, improvement of symptoms of irritable bowel
syndrome, remission in Crohn’s disease, and postantibi-
otic vulvovaginal candidiasis. Failure to show effects in
these studies may be due to lack of activity, improper
strain choice, or inadequate dose (35-40).
Recommending Probiotics
Although research documenting efficacy of probiotics is
still emerging, a growing number of consumers and
health care professionals are interested in trying probi-
otics to see if they can make a difference for them or their
clients. Commercial products are generally safe (see Fig-
ure 3), associated with few side effects, not too expensive,
and easy to try. Probiotics will likely be of interest to two
groups of people: those with specific health concerns for
which evidence of efficacy of probiotics is available, and
generally healthy people who are interested in probiotics
to help keep them healthy. The first group is motivated
and has a measurable outcome—symptom improvement.
Recommend products that have been tested for their spe-
cific health concern, and in the absence of those, choose
products that are high potency and safe. The second
group can be encouraged to try products shown to en-
hance immune function and reduction of risk of common
illnesses such as colds and diarrhea. This group might
also be interested in increasing the levels of live active
cultures in their diet. Such diets have not been evaluated
strictly, but could be recommended based on the emerg-
ing body of evidence that a variety of probiotics are ben-
eficial.
Adding fermented foods might seem like a good way to
increase the number of live bacteria to a diet. Unfortu-
nately, in the United States the number of commercially
available foods of this type is limited. Many fermented
foods do not contain live cultures as finished products. In
some cases this is due to the nature of the product: sour-
dough bread is baked and fermented meats are often
smoked or cooked. Or this may be due to typical consump-
tion patterns. Cheeses baked onto a pizza do not retain
any live cultures. But in some cases the lack of microbes
in foods is due to modern food processing approaches
designed to improve product consistency or shelf life (41).
 Genus, species, strain
Indication (commercial strain designation) Products (format)

Infant diarrhea L rhamnosus GG (LGG) Culturelle (capsule) www.culturelle.com

Inflammatory bowel conditions
(primary evidence in pouchitis)
Antibiotic associated diarrhea;
C difficile
Gut transit time
Keeping healthy
Atopic dermatitis (primary
evidence is prevention when
fed to newborn infants)
Lactose intolerance
Colic in infants
Immune support
Vaginal applications
Irritable bowel syndrome
symptoms
L casei DN114001 (Immunitas)
8-strain combination of 3 Bifidobacterium
strains, 4 Lactobacillus strains and S.
thermophilus
S cerevisiae (S. boulardii)
L rhamnosus GG
L casei DN114001
L acidophilus CL1285 plus L casei
B animalis DN173 010 (Bifidus regularis)
L reuteri ATCC 55730
L casei DN114001
L rhamnosus GG
Most strains L bulgaricus and/or S thermophilus
L reuteri ATCC 55730 (Protectis)
B lactis HN019 (HOWARU or DR10)
B lactis Bb-12
L casei DN114001
L rhamnosus GR-1 plus L reuteri RC-14
B infantis 35264 (Bifantis™)
Danimals (drinkable yogurt) www.danimals.com
DanActive (fermented milk) www.danactive.com
VSL#3 (powder) www.vsl3.com
Florastor (powder) www.florastor.com
Lalflor (capsule) www.institut-rosell.com
Culturelle (capsule) www.culturelle.com
Danimals (drinkable yogurt) www.danimals.com
DanActive (fermented milk) www.danactive.com
BioK⫹CL1285 (fermented milk, capsule)
www.biokplus.com
Activia (yogurt) www.activia.com
BioGaia Chewable Gut Health Tablets, BioGaia
Gut Health Probiotic Straws, www.everidis.com
DanActive (fermented milk) www.danactive.com
Culturelle (capsule) www.culturelle.com
Danimals (drinkable yogurt) www.danimals.com
All yogurts with live, active cultures
Reuteri drops www.biogaia.com
Strain sold as an ingredient for dairy and
supplement products—contact Danisco
www.danisco.com
Good Start Natural Cultures (infant formula)
www.verybestbaby.com/GoodStart/Overview.aspx
Yo-Plus (yogurt) www.yo-plus.com
DanActive (fermented milk) www.danactive.com
Fem-Dophilus (capsules) www.urexbiotech.com;
www.jarrow.com
Align (capsules) www.aligngi.com

Figure 2. Examples of somea probiotic products available in the United States. Evidence-based use recommendations should be obtained from the
manufacturer if not disclosed on the label. aDozens of probiotic products are commercially available. This is a partial list of products containing
strains supported by published, human studies.

Filtration of fermented beverages such as wine, beer, or
vinegar effectively removes remaining microbes. Pickles
purchased in the grocery store are usually not fermented,
but are produced through a brining process. Some cucum-
ber pickles marketed as deli pickles (eg, overnight dills or
half-sours) commonly found in big-city delicatessens do
have live lactic acid bacteria. Sauerkraut is a fermented
product, but it is heated or treated with preservatives
after fermentation. Some traditional fermented ethnic
foods such as kimchi (fermented cabbage) or tempeh (fer-
mented soy beans) produced on a small scale may still
harbor high numbers of the fermentation microbes (41).
The biggest category of foods in the United States that
contains live and active cultures is fermented dairy prod-
ucts, such as kefir, yogurt, and cheeses. These products
are a source of potentially beneficial, live bacteria, espe-
cially of the genus Lactobacillus. Many yogurts sold in
the United States today contain both starter cultures
and additional bacteria, usually Lactobacillus and/or
Bifidobacterium that are added for a presumed probiotic

March 2008 ● Journal of the AMERICAN DIETETIC ASSOCIATION 513

 What is a recommended dose?
Is daily consumption necessary?
Are they safe?
Are refrigerated products best?
Do all probiotics of the same type
function in the same way?
Many yogurts contain added sugar.
Doesn’t this negate any health benefits
from probiotics?
Some products contain dried probiotics.
Are they still alive?
Do we all naturally harbor probiotics?
What is the difference between live
active cultures and probiotics?
What information should product
manufacturers provide on probiotic
products?
No general recommendation can be made. The dose must be based on studies that show
an effect. This level can range widely. Some products are effective at 100 million cfu/
day; others are recommended at over 1 trillion cfu/day.
Almost all published human studies have used daily dosing for efficacy determination.
Consumption recommendations should be based on the regimen used in human studies
demonstrating the health benefit.
Probiotics that contain Lactobacillus, Bifidobacterium, Streptococcus thermophilus, and
Saccharomyces strains have an extensive safety record for use in the generally healthy
population. Other types of probiotics (eg, Enterococcus, Escherichia coli, and Bacillus)
should be considered for specific individuals. Clients who are immunocompromised,
recovering from surgery, or who have compromised gut integrity are at elevated risk for
infection from any source and should take probiotics only under the advice of a health
care provider.
Keeping probiotics alive to ensure product potency is a challenge to the probiotic
industry. In general, microbes survive better at lower temperatures. However,
technologies for keeping probiotics alive at room temperature have been developed by
product manufacturers. It is not necessarily the case that refrigerated products will be
superior to those that are not refrigerated. Choose products from reputable companies
that are labelled for viability “through the end of shelf life” and not “at time of
manufacture.”
No. Probiotics are described by their genus (eg, Lactobacillus), their species (eg,
rhamnosus), and their strain (eg, GG). This degree of specificity in describing a probiotic
is essential because effects can be strain-specific. For example, L rhamnosus GG may
have different effects than L rhamnosus GR-1. Look for probiotics that are supported by
strain-specific research.
There is no evidence that the sugar added to sweetened yogurt negates the health
benefits associated with the probiotics contained in the yogurt. Sugar is digested and
absorbed in the small intestine and would not be expected to interfere with microbial
effects further down the intestinal tract. However, studies comparing identical probiotic
products with and without added sugar have not been conducted.
If bacteria are dried and stabilized properly, they remain alive (although dormant) and
start to grow again after they reach the moist environment inside your body.
A great number and diversity of microbes are associated with the human body, but these
cannot be called probiotics until they have been isolated, tested, and shown to have a
beneficial health effect.
Live cultures are microbes associated with foods, often as food fermentation agents.
Many of these have not been directly tested for health benefits. Probiotics are live
microbes that have been shown to have a health effect. Also, some probiotics would not
typically be associated with foods (such as E coli), and as such would not typically be
referred to as a live culture.
1. Identification of the genus, species, and strain of each probiotic present in the product
2. Citations of published human studies have been conducted on the product or the
specific strains in the product
3. Assurance that the product contains the level of probiotic through the end of shelf life
as was shown to be effective for each strain in the published studies

Figure 3. Key questions and answers about probiotics. See www.usprobiotics.org for additional information.

effect. Unfortunately, most of these products do not dis-
close the levels or strain designations of added additional
bacteria, so it is not possible for consumers to know if the
product has been shown to be efficacious for specific ef-
fects. Because starter cultures are present at high levels
in all non– heat-treated yogurts, total counts of live cul-
tures, which is the basis for use of the National Yogurt
Association’s Live Active Culture Seal (http://www.
aboutyogurt.com/lacYogurt/), do not differentiate be-
tween starter cultures and added probiotic bacteria. Low
levels of probiotics could be masked by high levels of
starter bacteria. Therefore, fermented dairy products
may not be a potent source of viable probiotic bacteria. No
surveys reporting differential counts of starter cultures
compared to additional bacteria added for health effects
in commercial products have been published.

514 March 2008 Volume 108 Number 3

 Some new food products, including a cereal (www.
kashi.com/products/vive_original), chocolate bar and
granola bar (www.attunefoods.com/products/) containing
putative probiotics have recently entered the US market,
and may provide dietary alternatives. Specific questions
about probiotic content and support for efficacy, which
are not answered on product labels or Web sites likely
need to be addressed to the manufacturer directly. Some
questions to ask include:
● What published human studies have been conducted on
the product or the specific strains in the product?
● What benefits were observed in those studies?
● Is the product formulated to contain the same level of
probiotic through the end of shelf life as was shown to
be beneficial in the studies?
Dose
At this point in time it is not possible to accurately gen-
eralize about a minimum dose of probiotics that is needed
for an effect. The required dose varies for different strains
and the specific health effect under investigation. Studies
showing positive effects at levels below 100 million (108)
colony-forming units (cfu) per day are not common in the
published literature; levels much higher than this may be
needed for certain health effects. For example, although L
reuteri was effective at reducing workplace absences at a
dose of 108 cfu/day (33), the probiotic blend of eight
strains in the commercial product VSL#3 (VSL Pharma-
ceuticals Inc, Gaithersburg, MD) was effective at
1.8⫻1012 cfu/day (42). This four-log cycle difference in
recommended dosage highlights the inaccuracy in mak-
ing general dose recommendations for unspecified prod-
ucts.
It should also be noted that maintaining viability of a
probiotic, both in the product and once consumed, can be
a technological challenge. Probiotics are sensitive in a
strain-dependent manner to environmental exposures
such as heat, moisture, oxygen, and acid. Technologies for
keeping probiotics alive in products have been developed
by product manufacturers. Frequently this involves con-
trol during storage and packaging of temperature, mois-
ture, and oxygen. Once the package is opened, these
barriers are compromised. In general, microbes survive
better at lower temperatures, but properly stabilized non-
refrigerated products can maintain potency at room tem-
perature. With regard to survival after consumption, sta-
bility is strain-specific. Some microencapsulation or
coating technologies (eg, enteric coating) for probiotics
have been developed that improve probiotic survival after
ingestion through the acid environment of the stomach
(43). But as long as doses in products are based on studies
of the product conducted in human beings, the doses
should reflect any losses inherent to the probiotic as it
moves through the alimentary canal.
Product Labeling
Probiotic products in the United States include foods,
dietary supplements, and medical foods. Although health
claims are allowable on foods and supplements with ap-
proval of the US Food and Drug Administration (FDA),
no health claims have been approved for probiotics. Foods
and supplement products containing probiotics can dis-
play structure/function claims as long as the claims are
truthful and not misleading. In the United States, no
premarket approval of structure/function claims is re-
quired and no probiotic product has been recalled for
failure to adequately substantiate such a claim. The FDA
has provided guidance to manufacturers on what type of
substantiation it considers proper support for structure/
function claims (44). Making proper label claims of effi-
cacy for probiotic products has been reviewed by Sanders
and colleagues (45,46).
Several reports of probiotic products failing to meet
label claim with regard to levels of live microbe contained
in the product have been published (47). These results
serve as a warning that not all products are what they
claim to be. On August 24, 2007, the FDA issued a final
ruling establishing regulations to require current good
manufacturing practices for dietary supplements to be
phased in during the next few years. Although these
regulations do not address verification of efficacy claims,
they will hopefully improve the compositional quality (eg,
identity, purity, and strength) of probiotic supplements in
the US market.
Take Home Suggestions on Probiotics
Probiotics may be of use to people with specific health
concerns for which evidence of efficacy of probiotics is
available or to people interested in dietary modification to
help them stay healthy. Several products available in the
United States have documented efficacy for several
health targets (Figure 2). Not all products on the market
are backed by efficacy research in human beings; these
products should not be called probiotics. Increasing the
levels of live cultures from foods may be of interest to
those wishing to leverage benefits, such as immune en-
hancement, associated with many different probiotic
strains. Health effects are considered to be strain-specific
unless proven otherwise. Therefore, efficacy cannot be
presumed unless specific researched strains are con-
sumed at the proper doses. Dietary sources of live cul-
tures include fermented dairy products and a few new
functional foods on the market. Products should be used
according to manufacturers’ recommendations. Figure 3
provides quick answers to common questions about pro-
biotics.
PREBIOTICS
Understanding Prebiotics
Prebiotics are defined as food ingredients that promote
the growth or activity of a limited number of bacterial
species for the benefit of host health (48). In common
terms, prebiotics are food for bacterial species that are
considered beneficial for health and well-being. The bac-
terial species primarily of interest include those in the
Lactobacillus and Bifidobacterium genera. These broad
bacterial groups do not specifically refer to documented
probiotic strains. However, defined probiotic bacteria are
not necessarily excluded from those microbes that may
have the ability to use prebiotic fiber as a substrate. More
precisely, prebiotic refers to substances that have under-
gone extensive in vitro and in vivo testing across a num-
March 2008 ● Journal of the AMERICAN DIETETIC ASSOCIATION 515
ber of subject species, including human beings, to confirm
prebiotic fermentation characteristics. Furthermore, the
fermentation characteristics identifying a substance as
prebiotic should include nutraceutical effects that extend
beyond those of regular nutrition.
The majority of these effects are associated with opti-
mized colonic function and metabolism, such as an in-
crease in the expression or change in the composition of
short-chain fatty acids, increased fecal weight, a mild
reduction in luminal colon pH, a decrease in nitrogenous
end products and reductive enzymes, an increased ex-
pression of the binding proteins or active carriers associ-
ated with mineral absorption, and immune system mod-
ulation (49-58). These changes in the colonic microbiota,
their products, and their effects on host biochemistry and
histology form the cornerstone rationale of associating
health benefits with the use of prebiotic ingredients. Be-
cause it is beyond the scope of this article to describe each
of these health benefits in detail, the studies and reviews
referenced throughout this section can provide practitio-
ners with a solid foundation in the mechanisms that
account for the broad-based effects of prebiotic fibers.
The human diet may contain a variety of foods that
provide fermentable fiber. Localized fermentation is cru-
cial to the trophic needs of colonocytes, which derive the
majority of their nourishment from this source (59). Many
substances and foods are being declared prebiotic, based
on fermentability alone (60,61). Various whole foods are
also being equated to prebiotics because they contain a
mixture of fibers, some of which are fermentable (62,63).
This information is imprecise and confusing. Because
foods are complex items with broad metabolic and nutri-
tional effects, they should not be categorized as narrowly
as the prebiotic definition demands (64). Furthermore, all
macronutrients and their partially digested remnants ar-
riving in the colon are available as microbial substrate
and yield a variety of fermentation products of a highly
mixed nature, which may be either potentially beneficial
or detrimental to health (59). Therefore, the word prebi-
otic must always refer to specific, defined substances that
exhibit a particular, scientifically observed effect as
stated by the prebiotic definition. Fiber, and particularly
fermentable fiber, is crucial for good health. But prebiot-
ics are specialized ingredients targeted to influencing
specific bacteria, their fermentation end products, and
possible health effects on the host.
Prebiotic Sources and Their Efficacy
The Fructans. In vitro testing is not sufficient for prebiotic
qualification or claims of efficacy because this method
cannot approach the dynamic nature of colonic metabo-
lism. There are also method limitations that involve the
metabolism of the resident microflora as well as that of
the host. These factors contribute to wide variations in
measurable colony forming unit counts, short-chain fatty
acid and enzyme levels, and other measurements of out-
come (60). This is only part of the reason that research
results have been mixed with regard to some aspects of
prebiotic efficacy, especially in human beings (65). Many
factors can confound results, including the chemical com-
position of the proposed prebiotic, its fermentation pro-
file, the study design, the baseline distribution of a sub-
516 March 2008 Volume 108 Number 3
ject’s colonic microbiota, the methodologies used in
observing an effect in a particular subject group, and the
statistical constructs used to interpret the data (66).
Furthermore, many scientists, educators, and science
writers operate under the assumption that prebiotics are
homogeneous inulin-based oligosaccharides (60-64,67).
This misconception contributes to conflicting results in
the science and in the dissemination of faulty information
within the research and professional communities. Cur-
rently, the major group of prebiotics in use in the US food
supply is the fructans. Fructans are a group of naturally
occurring oligosaccharides and fructooligosaccharides
found in milligram quantities in onions, bananas, wheat,
artichokes, garlic, and other whole foods (68). They are
also extracted from chicory or manufactured from sucrose
for use in the food industry. Despite their similarities, the
fructans remain distinct from each other in origin, struc-
ture, and fermentation characteristics. An overview of
fructans, including short-chain fructooligosaccharides,
provides valuable information that helps clarify this
group of prebiotic ingredients (69).
Resistant Starch. Nonfructan prebiotics are also under in-
vestigation for their fermentation characteristics, prebi-
otic effect, and health benefits. In particular, resistant
starch has been the subject of numerous studies that
document a prebiotic effect, both as a single ingredient
and in combination with fructooligosaccharides. Resis-
tant starch is found in raw potatoes, cooked and cooled
starchy products (retrograded starch), and in unripe
fruits like bananas. Appreciable amounts of resistant
starch exist in many commercial food products due to
processing effects upon starch (70). Resistant starch is
also manufactured specifically for use in the food indus-
try. There are review articles that give an informative
overview on the various types of resistant starches and
their uses (71-73).
The bread and cereal categories are filled with products
that include meaningful amounts of resistant starch or
inulin for fiber content and sometimes energy reduction.
Although many products may not currently leverage this
content for structure/function label claims, it may be a
viable option for the future as the science develops and
consumer awareness expands. For now, high fiber con-
tent, coupled with good palatability and color profile is
sufficient to drive demand. It is reported that 20 g/day of
resistant starch is a minimum healthy dose (74). Resis-
tant starch may be difficult to recognize on food labels.
Some terms to look for are “corn starch,” “starch,” “mod-
ified food starch,” and “maltodextrin.” However, because
all starches and maltodextrins are not resistant to diges-
tion, consumers should also look for fiber claims, reduced-
energy claims, or reduced-carbohydrate claims to confirm
the presence of resistant starch.
In a recent human study, Bouhnik and colleagues (75)
reported on the efficacy of the most common prebiotic
ingredients currently in use, with a side-by-side human
in vivo comparison that provides useful information for
food and nutrition professionals. Bouhnik’s group found
that short-chain fructooligosaccharides, soybean oligosac-
charides, galactooligosaccharides, and type III resistant
starch measurably raised fecal counts of Bifidobacterium
species at reasonable dose ranges of 2.5 to 5 g/day within
7 days of administration. These are among the most com-
 Minimum
Inclusion Level
daily dose
Company Product Claim g/Serving Prebiotic type (g/d) Company Web site

Horizon Organic, Various Calcium absorption, 0.750 Short-chain 3 www.horizonorganic.com/

Boulder, CO immune benefits, fructooligosaccharides
improved digestion
Stonyfield Farms, Various Calcium absorption 1.0 to 4.0 Short- and long-chain 8 www.stonyfield.com
Londonderry, NH inulin
Lifeway Foods, Helios Nutrition’s Bifidogenesis, 2 Short- and long-chain 8 www.heliosnutrition.com
Morton Grove, IL Organic Kefir calcium absorption inulin
Kashi Company, Cereals, drink Fiber Check Short- and long-chain 8 www.kashi.com
La Jolla, CA mixes, cereal bars label inulin listed as soluble
fiber on Nutrition
Facts label
Abbott Nutrition, Ensure Fiber Fiber, digestive 1 Short-chain 3 www.ensure.com
Columbus, OH health fructooligosaccharides
South Beach Diet, Cereal bars, meal- Fiber Varies Oligofructose, inulin, 8 www.southbeachdiet.com/
Miami Beach, FL replacement bars, or combination kraft/kraft.asp
and snacks
Clif Bar, Inc, Clif Bar, Luna Bar, Fiber Varies Inulin, oligofructose 8 www.clifbar.com
Berkeley, CA Builder’s Bar
Abbott Nutrition, ZonePerfect Fiber 3 Fructooligosaccharides 3 www.zoneperfect.com
Columbus, OH shakes
Skinny Cow, Low-fat ice cream Fiber 3 Fructooligosaccharides 3 www.skinnycow.com
Nestlé SA, Vevey, sandwiches
Switzerland

Figure 4. Partial list of commercial food products containing prebiotics that are widely available to consumers.

monly found prebiotics in the food supply at present.
However this category of ingredients will continue to
expand as ingredient technology develops and the science
advances.
Medical Uses of Prebiotics
Effective prebiotics are widely available and frequently
used in enteral nutrition products. Prebiotic enrichment
of these liquid products is used as a means to provide
short-chain fatty acids to colonocytes via fermentation,
normalize and maintain bowel function, colon integrity,
and build colonization resistance in a hospital setting
(76). These characteristics make prebiotics appropriate
for use in patients with antibiotic-associated diarrhea;
various irritable bowel conditions, including colitis; and
for general bowel maintenance while receiving a formu-
lated diet for medical nutrition therapy (77). When used
in appropriate amounts, the effect of prebiotic fiber may
also lead to an alteration in nitrogen excretion that is
thought advantageous to renal patients (78,79). Patient
tolerance of these formulations and compatibility of the
prebiotic ingredient used in a range of enteral products
has been established, both experimentally and empiri-
cally (80).
The nonviscous nature of short-chain fructooligosac-
charides, which is the predominant prebiotic fiber used in
liquid enteral products, is not detrimental to the flow
characteristics that can be important if a feeding tube is
used to deliver nutrition. Prebiotics are currently found
in enteral products that are used with adult and pediatric
patients presenting with a wide range of medical condi-
tions, including diabetes, cancer, renal failure, pressure
ulcers, metabolic stress, trauma, and immunosuppres-
sion, and can be found in the Ross Medical Nutrition
Pocket Guide (81). However, most of the primary research
leading to the inclusion of prebiotics in these products
may be proprietary or minimally published. Wolf and
colleagues (82) provide an informative overview of the
medical uses of fructooligosaccharides at the levels found
in enteral products. The use of these products to provide
total nutrition will deliver efficacious amounts of prebi-
otic fiber to hospitalized patients, generally in the range
of 10 to 15 g/day. For patients not receiving formulated
diets, simply start with 1 g/day for the first week, increas-
ing by 1 g/week until a 3-g level is attained. This minimal
amount is supported in the research listed above and may
be slowly increased to the levels used in enteral nutrition
products safely. The maximum dose that is generally
recognized as safe for all persons older than age 1 year is
20 g, although much higher doses have also been sug-
gested as safe (83). It should also be remembered that

March 2008 ● Journal of the AMERICAN DIETETIC ASSOCIATION 517

 Minimum
effective
Company Product Prebiotic type Format dosea Company Web site

Nutraceutical Corp, Kal NutraFlora Short-chain Powder 1 tsp www.nutraceutical.com

Park City, UT FOS fructooligosaccharides
Nutraceutical Corp Solaray Short-chain chain Capsule 4 capsules www.nutraceutical.com
NutraFlora FOS fructooligosaccharides
GlaxoSmithKline, FiberChoice Inulin Chewable 4 tablets/drops www.fiberchoice.com/products/
Philadelphia, PA (variety of tablet/drop tablets.asp
formats)
Intelligent Nutrition SmartFiberStixx Oligofructose plus Powder 2 FiberStixx www.smartfiberstixx.com/
LLC, New Orleans, Inulin about_us.htm
LA
The Vitamin Shoppe, Miracle Fiber Inulin Powder 3 tsp in www.vitaminshoppe.com/store/en/
North Bergen, NJ divided doses browse/sku_detail.jsp?id⫽VS-2528
The Vitamin Shoppe NutraFlora FOS Short-chain Powder 1 tsp www.vitaminshoppe.com/store/en/
fructooligosaccharides browse/sku_detail.jsp?id⫽VS-2152
Life Enhancement Durk Pearson & High amylose Powder 1 tbsp www.life-enhancement.com/
Progducts Inc, Sandy Shaw’s resistant starch product.asp?id⫽600
Petaluma, CA Glycemic Control
Resistant Starch

Figure 5. Partial list of prebiotic supplement products. Products containing less than 500 mg prebiotic per serving were not included. aMinimum
dose for general prebiotic effect, according to published research.

prebiotics are food ingredients and not drug therapies or
vitamins, for which there are more rigid guidelines.
Therefore, recommendations will be more flexible and
tailored to the individual client.
Recommending Prebiotics for Nutrition Clients
With the broad use of prebiotic fiber in medical foods for
focused benefits, it follows that consumers and nutrition
clients in a variety of settings may also benefit from
these ingredients, which are available in foods and sup-
plements. Research conducted on human beings given
L acidophilus of an unidentified strain, both with and
without a prebiotic suggests that the overall effect of the
L acidophilus was enhanced by a coadministration of
short-chain fructooligosaccharides (84). These results im-
ply the usefulness of a blended approach that fits well
with the current availability of dairy products that are
enhanced with the inclusion of fructan-type prebiotics,
although the research may not have been conducted on a
synbiotic combination. The natural yogurt section of the
dairy case is replete with products containing various
levels of mixed short- and long-chain inulin and pure
short-chain fructooligosaccharides, though none of them
claim to be synbiotic. Although no food products that
contain a defined probiotic in proven amounts reported on
the label also contain a prebiotic at this time, dairy prod-
ucts may provide a convenient way to gain the benefits of
yogurt and other cultures with some level of probiotics
and prebiotics.
Consumers should be encouraged to read the labels to
ensure that an adequate dose of prebiotic fiber will be
consumed in 1 day. The dosage levels for most health
benefits will range from 3 g for short-chain fructooligo-
saccharides to 8 g for mixed short- and long-chain inulin,
although more may be safely consumed according to in-
dividual tolerance. Although 20 g resistant starch is rec-
ommended per day, low dose ranges of 2.5 to 5 g/day have
demonstrated a prebiotic effect, as discussed earlier. The
difference in dosing is due to the varying fermentation
profiles of prebiotic ingredients. Figure 4 provides effec-
tive dose and serving information on some the most com-
mon prebiotic-containing products used in the United
States.
Supplementary Prebiotics and Special Foods
Supplements may provide an easy way to boost prebiotic
fiber consumption, giving consumers a clear, convenient,
and foolproof way to obtain a particular type of prebiotic
and dose level. Prebiotic supplements can be found that
are clearly labeled, can be sprinkled directly on food;
stirred into beverages; or taken as capsules, tablets, or
chewables. Because the most commonly available prebi-
otics are water soluble and completely clear in water,
they are easily incorporated into most foods and are un-
detectable. Figure 5 gives a partial listing of prebiotic
supplement products.
Special foods such as sports drinks, weight-loss pow-
ders, ready-to-drink protein meal replacers, and nutrition
bars provide a popular way for people to obtain prebiotic
fiber. These food items often contain fructooligosaccha-
rides, some form of inulin, or resistant starch for their
fiber content and prebiotic advantages, although there

518 March 2008 Volume 108 Number 3

may be no prebiotic-associated label claims. But, again,
this is more a case of consumer-driven labeling. If a label
claim becomes attractive to the consumer, the prebiotic is
already built into the formulation, giving the manufac-
turer the ability to communicate additional product ben-
efits in the future. Consumers should check labels for
type and amount of prebiotic inclusion.
Regulation of Prebiotics
Because the FDA does not require premarket approval of
the structure/function label claims on any food or supple-
ment product, the guidance publications prepared by the
FDA for food manufacturers are open to very broad in-
terpretation (44). It is up to food and nutrition profession-
als and consumers alike to read labels and remain alert to
the differences between marketing puffery (or hype) and
factual nutrition and ingredient declarations, both of
which are displayed on food labels.
With regard to prebiotic claims, it is the recom-
mended current practice for food manufacturers who
are making structure/function claims to declare the
amount of prebiotic shown to provide a particular ben-
efit, in addition to the amount contained in one serving
of the product. Up to four servings may be required to
meet the level of demonstrated benefit. A wealth of
information about the way these products are pre-
sented, as well as the scientific references supporting
specific marketing claims is available on product man-
ufacturers’ company Web sites, some of which are
available in Figures 2 and 3. Web addresses are also
often available on product labels. Foods containing pre-
biotics may have claims on the label. However, many
food products contain appreciable amounts of prebiotic
fiber without label claims. In addition, some prebiotic-
enriched products may simply claim a higher fiber
level, rather than any nutraceutical effect.
CONCLUSIONS
Client recommendations for probiotics and prebiotics can
be made that reflect the sum of current knowledge and
practice. For general health, incorporating more probi-
otic-rich foods into diets may lead to better nutritional
status, improved gastrointestinal function, resistance to
getting sick, and overall improved health. However, con-
trolled studies measuring the effect of such diets over the
long term have not been conducted. In addition, some
therapeutic functions have been identified for probiotics.
In this case, check that products contain the types and
levels of probiotic shown to produce the desired effect.
Because the FDA does not review claims of efficacy, sub-
stantiation of benefits should be verified with the manu-
facturer.
Prebiotics are valuable dietary additions for modulat-
ing the growth and activity of specific bacterial species in
the colon that are considered health-supporting. Prebiot-
ics may also provide support for the survival and growth
of intentionally consumed bacterial species, including
some probiotic strains. The research suggests that sub-
strate specificity may be important in considering prebi-
otic products and dose levels. The use of products con-
taining prebiotic fibers or pure prebiotic powders should
be consistent, and of adequate inclusion or dose levels to
ensure desired and continued benefits.
Probiotics and prebiotics can be combined to form syn-
biotic products that presumably can impart the beneficial
effects of both ingredients. There is a great need for
studies documenting any added benefits or health effects
from this combination of ingredients. Nonetheless, in the
United States, some products currently contain synbiotic
elements in the dairy case, although they may not be
labeled as such. Dairy may be a logical first place to
position these products because most dairy products con-
tain nutrients important to the survival of the majority
probiotic species and provide the proper pH range for
both pro- and prebiotic stability under refrigeration con-
ditions. Scientific verification of benefits for combinations
of pro- and prebiotics will be critical to the success of the
synbiotic concept.
This work was based on the session “Probiotics and pre-
biotics: How can they help your clients?” presented at the
2006 Food & Nutrition Conference & Expo of The Amer-
ican Dietetic Association, September 16-18, 2006, Hono-
lulu, HI, and was supported by the Dairy Council of
California. The opinions expressed in this article are
those of the authors and do not necessarily represent the
views of Dairy Council of California.
L. C. Douglas received honoraria and/or support from
September 2006 to January 31, 2007, from the Dairy
Council of California and the Dannon Institute in support
of an educational session at the 2006 Food & Nutrition
Conference & Expo of The American Dietetic Association,
September 16-18, 2006, Honolulu, HI, and both authors
will receive an honorarium from the Dairy Council of
California in support of their work on this article. M. E.
Sanders received payment or honoraria for consulting
services or honoraria for speaking engagements between
July 1, 2005, and January 30, 2007 from for-profit and
not-for-profit companies interested in probiotics.
References
1. Food and Agriculture Organization of the United Nations and World
Health Organization. Health and nutritional properties of probiotics in
food, including powder milk with live lactic acid bacteria. World Health
Organization Web site. http://www.who.int/foodsafety/publications/fs_
management/en/probiotics.pdf. Accessed December 17, 2006.
2. Dixon B. Secrets of the Bulgarian bacillus. Lancet Infect Dis. 2002;
2:260.
3. Backhed F, Ley RE, Sonnenburg JL, Peterson DA, Gordon JI.
Host-bacterial mutualism in the human intestine. Science. 2005;
307:1915-20.
4. Eckburg PB, Bik EM, Bernstein CN, Purdom E, Dethlefsen L, Sargent
M, Gill SR, Nelson KE, Relman DA. Diversity of the human intestinal
microbial flora. Science. 2005;308:1635-1638.
5. Bengmark S. Bacteria for optimal health. Nutrition. 2000;16:611-615.
6. Guarner F, Bourdet-Sicard R, Brandtzaeg P, Gill HS, McGuirk P, van
Eden W, Versalovic J, Weinstock JV, Rook GA. Mechanisms of dis-
ease: The hygiene hypothesis revisited. Nat Clin Pract Gastroenterol
Hepatol. 2006;3:275-284.
7. Simakachorn N, Pichaipat V, Rithipornpaisarn P, Kongkaew C, Tong-
pradit P, Varavithya W. Clinical evaluation of the addition of lyoph-
ilized, heat-killed Lactobacillus acidophilus LB to oral rehydration
therapy in the treatment of acute diarrhea in children. J Pediatr
Gastroenterol Nutr. 2000;30:68-72.
8. Sanders ME. 10 myths about probiotics. Prepared Foods. 2005;7:67-73.
9. Sanders ME. Probiotics: Considerations for human health. Nutr Rev.
2003;61:91-99.
10. Marteau P, Seksik P, Lepage P, Doré J. Cellular and physiological
effects of probiotics and prebiotics. Mini Rev Med Chem. 2004;4:889-
896.
March 2008 ● Journal of the AMERICAN DIETETIC ASSOCIATION 519
11. Rastall RA, Gibson GR, Gill HS, Guarner F, Klaenhammer TR, Pot B,
Reid G, Rowland IR, Sanders ME. Modulation of the microbial ecology
of the human colon by probiotics, prebiotics and synbiotics to enhance
human health: an overview of enabling science and potential appli-
cations. FEMS Microbiol Ecol. 2005;52:145-152.
12. Floch MH, Montrose DC. Use of probiotics in humans: An analysis of
the literature. Gastroenterol Clin North Am. 2005;34:547-570.
13. Jenkins B, Holsten S, Bengmark S, Martindale R. Probiotics: A prac-
tical review of their role in specific clinical scenarios. Nutr Clin Pract.
2005;20:262-270.
14. Marco ML, Pavan S, Kleerebezem M. Towards understanding molec-
ular modes of probiotic action. Curr Opin Biotechnol. 2006;17:204-
210.
15. Plummer S, Weaver MA, Harris JC, Dee P, Hunter J. Clostridium
difficile pilot study: Effects of probiotic supplementation on the inci-
dence of C. difficile diarrhoea. Int Microbiol. 2004;7:59-62.
16. Joint Food and Agriculture Organization of the United Nations/World
Health Organization Working Group on Drafting Guidelines for the
Evaluation of Probiotics in Food. Guidelines for the Evaluation of
Probiotics in Food. Swedish South Asian Network for Fermented Food
Web site. http://www.fermented-foods.net/wgreport2.pdf. Accessed
December 17, 2006.
17. Gill HS. Probiotics to enhance anti-infective defences in the gastroin-
testinal tract. Best Pract Res Clin Gastroenterol. 2003;17:755-773.
18. Bengmark S. Use of some pre-, pro- and synbiotics in critically ill
patients. Best Pract Res Clin Gastroenterol. 2003;17:833-848.
19. Tamboli CP, Caucheteux C, Cortot A, Colombel JF, Desreumaux P.
Probiotics in inflammatory bowel disease: A critical review. Best Pract
Res Clin Gastroenterol. 2003;17:805-820.
20. Mimura T, Rizzello F, Helwig U, Poggioli G, Schreiber S, Talbot IC,
Nicholls RJ, Gionchetti P, Campieri M, Kamm MA. Once daily high
dose probiotic therapy (VSL#3) for maintaining remission in recur-
rent or refractory pouchitis. Gut. 2004;53:108-114.
21. Van Niel CW, Feudtner C, Garrison MM, Christakis DA. Lactobacil-
lus therapy for acute infectious diarrhea in children: A meta-analysis.
Pediatrics. 2002;109:678-684.
22. Kalliomaki M, Salminen S, Poussa T, Arvilommi H, Isolauri E. Pro-
biotics and prevention of atopic disease: 4-year follow-up of a random-
ised placebo-controlled trial. Lancet. 2003;361:1869-1871.
23. de Vrese M, Stegelmann A, Richter B, Fenselau S, Laue C, Schrezen-
meir J. Probiotics—Compensation for lactase insufficiency. Am J Clin
Nutr. 2001;73(suppl):S421-S429.
24. Anukam K, Osazuwa E, Ahonkhai I, Ngwu M, Osemene G, Bruce AW,
Reid G. Augmentation of antimicrobial metronidazole therapy of bac-
terial vaginosis with oral probiotic Lactobacillus rhamnosus GR-1 and
Lactobacillus reuteri RC-14: Randomized, double-blind, placebo con-
trolled trial. Microbes Infect. 2006;8:1450-1454.
25. Anukam KC, Osazuwa E, Osemene GI, Ehigiagbe F, Bruce AW, Reid
G. Clinical study comparing probiotic Lactobacillus GR-1 and RC-14
with metronidazole vaginal gel to treat symptomatic bacterial vagi-
nosis. Microbes Infect. 2006;8:2772-2776.
26. Saggioro A. Probiotics in the treatment of irritable bowel syndrome.
J Clin Gastroenterol. 2004;38(suppl 6):S104-S106.
27. Niedzielin K, Kordecki H, Birkenfeld B. A controlled, double-blind,
randomized study on the efficacy of Lactobacillus plantarum 299V in
patients with irritable bowel syndrome. Eur J Gastroenterol Hepatol.
2001;13:1143-1147.
28. Cremonini F, Di Caro S, Nista EC, Bartolozzi F, Capelli G, Gasbarrini
G, Gasbarrini A. Meta-analysis: The effect of probiotic administration
on antibiotic-associated diarrhoea. Aliment Pharmacol Ther. 2002;16:
1461-1467.
29. Lionetti E, Miniello VL, Castellaneta SP, Magista AM, de Canio A,
Maurogiovanni G, Ierardi E, Cavallo L, Francavilla R. Lactobacillus
reuteri therapy to reduce side effects during anti-Helicobacter pylori
treatment in children: A randomized placebo controlled trial. Aliment
Pharmacol Ther. 2006;24:1461-1468.
30. Nase L, Hatakka K, Savilahti E, Saxelin M, Ponka A, Poussa T,
Korpela R, Meurman JH. Effect of long-term consumption of a probi-
otic bacterium, Lactobacillus rhamnosus GG, in milk on dental caries
and caries risk in children. Caries Res. 2001;35:412-420.
31. Hatakka K, Savilahti E, Ponka A, Meurman JH, Poussa T, Nase L,
Saxelin M, Korpela R. Effect of long-term consumption of probiotic
milk on infections in children attending day care centres: Double
blind, randomised trial. BMJ. 2001;322:1327.
32. de Vrese M, Winkler P, Rautenberg P, Harder T, Noah C, Laue C, Ott
S, Hampe J, Schreiber S, Heller K, Schrezenmeir J. Effect of Lacto-
bacillus gasseri PA 16/8, Bifidobacterium longum SP 07/3, B. bifidum
MF 20/5 on common cold episodes: A double blind, randomized, con-
trolled trial. J Clin Nutr. 2005;24:481-491.
520 March 2008 Volume 108 Number 3
33. Tubelius P, Stan V, Zachrisson A. Increasing workplace healthiness
with the probiotic Lactobacillus reuteri: A randomised, double-blind
placebo-controlled study. Environ Health. 2005;7;4:25.
34. 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.
35. Thomas MR, Litin SC, Osmon DR, Corr AP, Weaver AL, Lohse CM.
Lack of effect of Lactobacillus GG on antibiotic-associated diarrhea: A
randomized, placebo-controlled trial. Mayo Clin Proc. 2001;76:883-
889.
36. Anderson AD, McNaught CE, Jain PK, MacFie J. Randomised clinical
trial of synbiotic therapy in elective surgical patients. Gut. 2004;53:
241-245.
37. McNaught CE, Woodcock NP, MacFie J, Mitchell CJ. A prospective
randomised study of the probiotic Lactobacillus plantarum 299V on
indices of gut barrier function in elective surgical patients. Gut. 2002;
51:827-831.
38. O’Sullivan MA, O’Morain CA. Bacterial supplementation in the irri-
table bowel syndrome. A randomised double-blind placebo-controlled
crossover study. Dig Liver Dis. 2000;32:294-301.
39. Marteau P, Lemann M, Seksik P, Laharie D, Colombel JF, Bouhnik Y,
Cadiot G, Soule JC, Bourreille A, Metman E, Lerebours E, Carbonnel
F, Dupas JL, Veyrac M, Coffin B, Moreau J, Abitbol V, Blum-Sperisen
S, Mary JY. Ineffectiveness of Lactobacillus johnsonii LA1 for pro-
phylaxis of postoperative recurrence in Crohn’s disease: A random-
ised, double blind, placebo controlled GETAID trial. Gut. 2006;55:842-
847.
40. Pirotta M, Gunn J, Chondros P, Grover S, O’Malley P, Hurley S,
Garland S. Effect of Lactobacillus in preventing post-antibiotic vul-
vovaginal candidiasis: A randomised controlled trial. BMJ. 2004;329:
548.
41. Breidt F Jr, McFeeters RF, Diaz-Muniz I. Fermented vegetables. In:
Doyle MP, Beuchat LR, eds. Food Microbiology: Fundamentals and
Frontiers. 3rd ed. Washington, DC: ASM Press; 2007:783-793.
42. Mimura T, Rizzello F, Helwig U, Poggioli G, Schreiber S, Talbot IC,
Nicholls RJ, Gionchetti P, Campieri M, Kamm MA. Once daily high
dose probiotic therapy (VSL#3) for maintaining remission in recur-
rent or refractory pouchitis. Gut. 2004;53:108-114.
43. Champagne CP, Fustier P. Microencapsulation for the improved de-
livery of bioactive compounds into foods. Curr Opin Biotechnol. 2007;
18:184-190.
44. Center for Food Safety and Applied Nutrition Office of Nutritional
Products, Labeling, and Dietary Supplements. Guidance for Industry:
Substantiation for Dietary Supplement Claims Made Under Section
403(r) (6) of the Federal Food, Drug, and Cosmetic Act. US Food
and Drug Administration Web site. http://www.cfsan.fda.gov/⬃dms/
dsclmgui.html. Accessed December 17, 2006.
45. Sanders ME, Heimbach J. Functional foods in the USA: Emphasis on
probiotic-containing foods. Food Sci Technol Bull Funct Foods. 2004;
1:1-10.
46. Sanders ME, Tompkins T, Heimbach J, Kolida S. Weight of evidence
needed to substantiate a health effect for probiotics and prebiotics:
Scientific and regulatory considerations in Canada, EU, and US. Eur
J Nutr. 2004;44:303-310.
47. Hamilton-Miller JM, Shah S. Deficiencies in microbiological quality
and labelling of probiotic supplements. Int J Food Microbiol. 2002;
72:175-176.
48. Gibson GR, Roberfroid MB. Dietary modulation of the human colonic
microbiotia: Introducing the concept of prebiotics. J Nutr. 1995;125:
1401-1412.
49. Bournet FR, Brouns F, Tashiro Y, Duvillier V. Nutritional aspects of
short-chain fructooligosaccharides: Natural occurrence, chemistry,
physiology, and health implications. Dig Liver Dis. 2002;34(suppl
2):S111-S120.
50. Hidaka H, Hirayama M, Tokunaga T, Eida T. The effects of undigest-
ible fructooligosaccharides on intestinal microflora and various phys-
iological functions on human health. Adv Exp Med Biol. 1990;270:105-
117.
51. Tokunaga T. Novel physiological function of fructooligosaccharides.
Biofactors. 2004;21:89-94.
52. Scheppach W, Luehrs H, Menzel T. Beneficial health effects of low-
digestible carbohydrate consumption. Br J Nutr. 2001;85(suppl):S23-
S30.
53. Grizard D, Barthomeuf C. Non-digestible oligosaccharides used as
prebiotic agents: Mode of production and beneficial effects on animal
and human health. Reprod Nutr Dev. 1999;39:563-588.
54. Flamm G, Glinsmann W, Kritchevsky D, Prosky L, Roberfroid M.
Inulin and oligofructose as dietary fiber: A review of the evidence. Crit
Rev Food Sci Nutr. 2001;41:353-362.
55. Pool-Zobel B, van Loo J, Rowland I, Roberfroid MB. Experimental
evidences on the potential of prebiotic fructans to reduce the risk of
colon cancer. Br J Nutr. 2002;87(suppl 2):S273-281.
56. Cummings JH, Macfarlane GT, Englyst HN. Prebiotic digestion and
fermentation. Am J Clin Nutr. 2001;73(suppl 2):S415-S420.
57. Roberfroid MB. Health benefits of non-digestible oligosaccharides.
Adv Exp Med Biol. 1997;427:211-219.
58. Forchielli ML, Walker WA. The role of gut-associated lymphoid tis-
sues and mucosal defence. Br J Nutr. 2005;93(suppl 1):S41-S48.
59. Priebe MG, Vonk RJ, Sun X, He T, Harmsen HJM, Welling GW. The
physiology of colonic metabolism. Possibilities for interventions with
pre- and probiotics. Eur J Nutr. 2002;41(suppl 1):S2-S10.
60. Blaut M. Relationship of prebiotics and food to intestinal microflora.
Eur J Nutr. 2002;41(suppl 1):S11-S16.
61. Winter D. Probiotic and prebiotic foods. Baylor Health Care System Web
site. http://www.baylorhealth.com/healthinformation/healthsource/2005/
march/03-21-mon.htm. Accessed December 17, 2006.
62. Dixon S. Prebiotics and probiotics: What are they and why should I
eat them? University of Michigan Comprehensive Cancer Center
Web site. http://www.cancer.med.umich.edu/news/pro09spr02.htm.
Accessed December 17, 2006.
63. Charalampopoulos D, Wang R, Pandiella SS, Webb C. Application of
cereals and cereal components in functional foods: A review. Int J
Food Microbiol. 2002;79:131-141.
64. Slavin J. Why whole grains are protective: Biological mechanisms.
Proc Nutr Soc. 2003;62:129-134.
65. Tahiri M, Tressol JC, Arnaud J, Bournet F, Bouteloup-Demange C,
Feillet-Coudray C, Ducros V, Pepin D, Brouns F, Rayssiguier AM,
Coudray C. J Bone Miner Res. 2001;16:2152-2160.
66. Scholz-Ahrens KE, Schaafsma G, van den Heuvel EG. Effects of
prebiotics on mineral metabolism. Am J Clin Nutr. 2001;73(suppl):
459S-464S.
67. Brugger A. Inulin studies in humans: Overview of heath benefits. US
Pharmacist Web Site. http://www.uspharmacist.com/oldformat.asp?
url⫽publish/content/8_1862.htm. Accessed December 17, 2006.
68. Chow J. Probiotics and prebiotics: A brief overview. J Ren Nutr.
2002;12:76-86.
69. Douglas LC. Prebiotic overview. Nutraceuticals World. 2003;6:80-83.
70. Resistant starch—Questions and answers. British Nutrition Foundation
Web site. http://www.nutrition.org.uk/upload/Resistant%20Starch(1).
pdf. Accessed April 16, 2007.
71. Jacobasch G, Schmied D, Kruschewski M, Schmehl K. Dietary resis-
tant starch and chronic inflammatory bowel diseases. Int J Colorectal
Dis. 1999;14:201-211.
72. Topping DL, Clifton FM. Short-chain fatty acids and human colonic
function: Roles of resistant starch and nonstarch polysaccharides.
Physiol Rev. 2001;81:1031-1064.
73. Brown IL. Applications and uses of resistant starch. J AOAC Int.
2004;87:727-732.
74. Cassidy A, Bingham SA, Cummings JH. Starch intake and colorec-
tal cancer risk: An international comparison. Br J Cancer. 1994;
69:119-125.
75. Bounik Y, Raskine L, Simoneau,G, Vicaut E, Neut C, Flourie B,
Brouns F, Bournet FR. The capacity of nondigestible carbohydrates to
stimulate fecal bifidobacteria in healthy humans: A double-blind,
randomized, placebo-controlled, parallel-group, dose-response rela-
tion study. Am J Clin Nutr. 2004;80:1658-1664.
76. Whelan K, Judd PA, Preedy VR, Simmering R, Jann A, Taylor MA.
Fructooligosaccharides and fiber partially prevent the alterations in
fecal microbiotia and short-chain fatty acid concentrations caused by
standard enteral formula in healthy humans. J Nutr. 2005;135:1896-
1902.
77. Seidner DL, Lashner BA, Brzezinski A, Banks PL, Goldblum J, Fiocchi
C, Katz J, Lichtenstein GR, Anton PA, Kam LY, Garleb KA, Demichele
SJ. An oral supplement enriched with fish oil, soluble fiber, and antioxi-
dants for corticosteroid sparing in ulcerative colitis: A randomized, con-
trolled trial. Clin Gastroenterol Hepatol. 2005;3:358-369.
78. Younes H, Alphonse JC, Hadj-Adbelkader M, Remesy C. Fermentable
carbohydrates and digestive nitrogen excretion. J Ren Nutr. 2001;3:
139-148.
79. Younes H, Garleb K, Behr S, Remesy C, Demigne C. Fermentable
fibers or oligosaccharides reduce urinary nitrogen excretion by in-
creasing urea disposal in the rat cecum. J Nutr. 1995;125:1010-1016.
80. Cockram DB, Hensley MK, Rodriguez M, Agarwal G, Wennberg A,
Ruey P, Ashback D, Hebert L, Kunau R. Safety and tolerance of
medical nutritional products as sole sources of nutrition in people on
hemodialysis. J Ren Nutr. 1998;8:25-33.
81. Ross Products Division. Ross Medical Nutrition Pocket Guide. Colum-
bus, OH: Abbot Laboratories; 2005.
82. Wolf BW, Chow JM, Garleb KA. Medical foods and fructooligosaccha-
rides. In: Dimitriu S, ed. Polysaccharides: Structural Diversity and
Functional Versatility. 2nd ed. New York, NY: Marcel Dekker; 2005:
853-866.
83. US Food and Drug Administration, Center for Food Safety and Ap-
plied Nutrition, Office of Food Additive Safety. Agency GRAS re-
sponse letter. US Food and Drug Administration Web site. http://
www.cfsan.fda.gov/⬃rdb/opa-g118.html. Accessed on April 16, 2007.
84. Swanson KS, Grieshop CM, Flickinger EA, Bauer LL, Wolf BW,
Chow J, Garleb KA, Williams JA, Fahey GC Jr. Fructooligosaccha-
rides and Lactobacillus acidophilus modify bowel function and
protein catabolites excreted by healthy humans. J Nutr. 2002;132:
3042-3050.
March 2008 ● Journal of the AMERICAN DIETETIC ASSOCIATION 521