Prebiotics Probiotics PDF

od International Life Sciences Institute
ILSI EUROPE CONCISE MONOGRAPH SERIES
PROBIOTICS, PREBIOTICS
AND THE GUT MICROBIOTA
International Life
Sciences Institute
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PROBIOTICS, PREBIOTICS
AND THE GUT MICROBIOTA
by
Nino Binns
© 2013 ILSI Europe
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Printed in Belgium
D/2013/10.996/36
ISBN: 9789078637394
ISSN 2294-5490
CONTENTS
FOREWORD 1
INTRODUCTION 2
ROLE OF THE GI TRACT MICROBIOTA IN HEALTH AND DISEASE 4
Microbiota of the GI tract 4
Bacterial fermentation and metabolism 6
The GI epithelial barrier and immune system 8
Techniques for exploring the GI microbiota 10
THE PROBIOTIC CONCEPT 11
Definition and history 11
Selection of probiotic candidates 12
Characterisation and taxonomy 12
Safety 13
Application of probiotics in food 14
THE PREBIOTIC CONCEPT 14
Definition and history 14
Characterisation of prebiotic ingredients 14
Criteria for prebiotic selection 15
Application of prebiotics in food 15
HEALTH EFFECTS OF PREBIOTICS AND PROBIOTICS 16
Research challenges 16
Impact on the GI tract of prebiotics and probiotics 16
Impact on the GI tract specific to prebiotics 18
Impact on the GI tract specific to probiotics 20
Impact on the immune responses 20
PROBIOTICS AND PREBIOTICS: MECHANISMS OF ACTION 23
Overall mechanism 23
GI tract and its microbiota 23
Cross-talk with the host 25
OVERALL CONCLUSIONS 27
ABBREVIATIONS 29
GLOSSARY 30
SOURCE MATERIAL AND FURTHER READING 31
Author: Nino Binns, NB Consulting (UK)

Scientific Editors: Glenn. R. Gibson, University of Reading, (UK);
Mary Ellen Sanders, International Scientific Association for Pro & Prebiotics (US)
Scientific Reviewers: Nathalie Delzenne, Université Catholique de Louvain (BE) and Lorenzo Morelli, Catholic University of Piacenza, (IT)
Concise Monograph Series Editor: John Howlett (UK)
Coordinators: Agnès Méheust, Massimo Ambrosio and Alessandro Chiodini, ILSI Europe (BE)
Probiotics, Prebiotics and the Gut Microbiota 1
FOREWORD
Since the introduction of the concept of functional foods in the risk of disease. Instead of testing clinical endpoints of
Japan in the 1980s, there has been growing interest in the reduction in disease, in nutritional intervention studies it is
concept of prebiotics and probiotics, and the synergistic the markers of health or markers of risk of disease that need
combination thereof, called synbiotics, and their role in to be checked and validated. Influencing the biomarkers
human nutrition. Pre- and probiotics are now commonly of disease risk often requires an in-depth understanding of
found in a range of products for infants, young children and the underlying mechanisms. This is where future research in
adults. What is it that makes the consumer interested in pre- and probiotic science will add to existing knowledge
these ingredients? By definition, both pre- and probiotics and evidence. With their complexity and the complexity
should convey health benefits. The general population is of the systems with which they interact (the intestinal
increasingly interested in maintenance of health and self- microbiota, the immune system, etc.), understanding the
care and this may explain the consumers’ interest. mechanisms is scientifically a challenge.
Both pre- and probiotics elicit their effects, at least to some However, the scientific understanding of pre- and
extent, through modulation of the intestinal microbiota probiotic mechanisms has grown substantially in the
(formerly called microflora). The results of multidisciplinary past decade and efforts in the field are increasing,
research efforts to understand the composition and making us confident that further scientific knowledge will
function of the intestinal microbiota, as well as the role be generated. So far, evidence for the many potential
of pre- and probiotics, have recently been published. A health benefits of different pro- and prebiotics has been
summary of these findings is therefore both appropriate, documented, the effects very often being strain- and
in the context of pre- and probiotics, and timely. product-specific. Emerging physiological and analytical
tools embedded in a multidisciplinary research setting
Because of the lack of easily understandable and objective
will enable the elucidation of further mechanisms. The
information on the topic for the interested non-specialist
latter will be a part of the better understanding of pre-,
life scientist, ILSI Europe Task Forces on both Prebiotics
pro- and synbiotic health effects.
and Probiotics decided to initiate the writing of a Concise
Monograph with input from experts in the field. We are convinced that this Concise Monograph, based on
sound scientific evidence, will be an important contribution
The purpose of the monograph is to discuss in
in informing a wide audience about the concepts of pre-,
understandable terms the current abundant scientific
pro- and synbiotic nutrition.
knowledge on prebiotics, probiotics and the intestinal
microbiota, including the resulting effects on the host.
The monograph does not address the detailed regulatory Bernd Stahl
aspects of the topic. The challenge in nutritional sciences is Danone Research, Germany
not to tackle disease with a pharmaceutical approach, but Arthur Ouwehand
rather to maintain and support health and thereby reduce DuPont Nutrition and Health, Finland
2 Concise Monograph Series
INTRODUCTION consuming large amounts of fermented milk products

that contained Lactobacillus bacteria (“soured milk”)
could prolong and improve the quality of life because
Microbes, or micro-organisms, include bacteria, fungi, these bacteria entered the colon and limited the activities
yeasts and algae. They can be found everywhere on of undesirable microbes. Metchnikoff therefore saw the
Earth, including hostile environments like volcanoes, intestinal tract as an organ that could be manipulated
the ocean bed and deserts. They are incredibly diverse to improve health by adding exogenous bacteria to
and have adapted over millions of years to occupy their the gut. As a result, commercial yogurts and fermented
own particular niches. As far as humans are concerned, milks gained some popularity after the First World War,
microbes are best known for their role in causing but it was not until the 1980s that the sales of products
disease, but their power has also been harnessed for containing probiotics began to grow rapidly - first in
millennia to the benefit of humankind. They are used Japan and then extending to Europe during the 1990s.
in the production of fermented foods including dairy Probiotic bacteria may be defined as ‘live micro-
products, breads, vegetables and, of course, wines and organisms which, when administered in adequate
beers to name but a few. Owing to their potential for amounts, confer a health benefit on the host’ (FAO/WHO
very selective action, microbes are also crucial to the 2001). They can interact with commensal bacteria and
development and production of pharmaceuticals such can also have a direct impact on the host. Disentangling
as antibiotics and to the production of food ingredients these interactions is one of the key challenges for future
such as vitamins and citric acid. Microbes are also research. Other key challenges are to understand their
involved in the production of many other chemicals and mechanisms of action, to elucidate more specifically
enzymes and are used in waste processing. which probiotic strains can offer which health benefits
Most of the 1014 bacteria in the gut are found in the large and to define the intake levels needed to achieve those
intestine (colon) and, over the past 30 years or more, effects.
interest in the gut microbial population – the microbiota The prebiotic concept developed more recently. The
– and its environment has intensified. Numerous Japanese were the first to recognise the value of non-
research studies have shown that, far from being passive digestible oligosaccharides, initially in animal feed
inhabitants of the gastrointestinal (GI) tract, the habitual where their addition to the feed of piglets helped relieve
residents of the gut (commensal micro-organisms) and prevent scouring (diarrhoea). Japanese researchers
interact with their host in a very intricate manner. They also recognised the value of oligosaccharides in human
may modulate the effect of potentially harmful bacteria, milk and later demonstrated that consumption of fructo-
impact the host’s GI tract, digestion, metabolism and oligosaccharides and galacto-oligosaccharides led to an
immune system, and might even influence functions increase in intestinal bifidobacteria and stimulated their
beyond the gut. growth in the human gut. However, it was not until 1995
The concept that food-borne bacteria can be beneficial that the scientific concept for human gut microbiota
to health emerged at the turn of the twentieth century modulation by “prebiotics” was introduced. Since then,
and is usually attributed to Nobel Prize-winning a wealth of research information has accumulated. A
Russian scientist Ilya Metchnikoff. He hypothesised that prebiotic may be defined as “a selectively fermented
ingredient that results in specific changes in the

composition and/or activity of the gastrointestinal
microbiota, thus conferring benefit(s) upon host health”
(Gibson – et al., 2011).
Today, over 60% of functional food products are directed
towards digestive health, with prebiotics and probiotics
probably being the most common, worldwide. Probiotics
and prebiotics target the host through the gut by distinct
as well as complementary mechanisms of actions.
This Concise Monograph will describe the concepts of
probiotics and prebiotics for use in the human diet and
will explore the scientific basis for potential human health
benefits. In general, research to date indicates that these
food ingredients offer possible health benefits and do
not pose any risks to health. Indeed, a range of naturally
occurring prebiotics and a number of probiotics, primarily
from the genera Lactobacillus, Bifidobacterium and
Saccharomyces, have long been consumed throughout
the world either as part of traditional diets or in the form
of modern functional foods.
ROLE OF THE GI TRACT The most common of the numerous bacteria harboured
in the oral cavity are streptococci. Bacteria do not
MICROBIOTA IN HEALTH colonise the stomach in high numbers because of its
AND DISEASE low pH and rapid transit; nevertheless, in the healthy
adult stomach there may be around 103 bacteria in every
millilitre (ml) of stomach contents, the main inhabitants
Microbiota of the GI tract being lactobacilli, enterococci, Helicobacter and bacilli.
The duodenum also tends to be acidic with a rapid
Bacteria are normal cohabitants with humans and are transit but additionally receives pancreatic secretions
associated with many tissues including the skin, the vaginal and bile that create a hostile environment for microbes.
tract, the respiratory tract and the GI tract. Microbes occur Here, lactobacilli and streptococci predominate, with
throughout the GI tract (Figure 1), the majority residing in total numbers of bacteria at 102–104 per ml. Along the
the colon. jejunum and particularly the ileum there is a gradual
increase in the numbers and diversity of bacteria present.
FIGURE 1. Finally, the colon contains the majority of GI microbes,
The human gastrointestinal tract. CFU, colony-forming with as many as 1011 organisms per ml.
units. (Adapted from Sanders, 2007)
Prior to birth, micro-organisms are absent from the GI
tract but quickly colonise it during and after birth. Exactly
which microbiota develops is dependent on factors such
as the method of delivery and the environment in which
birth takes place, the mother’s microbiota and the manner
of feeding. Bifidobacteria dominate the faecal microbiota
of healthy breast-fed infants whereas healthy formula-fed
infants have a wider range of organisms present, including
bifidobacteria, bacteroidetes, clostridia, enterobacteria
and streptococci. At weaning, there are changes in the
numbers and diversity of the gut microbiota, which
gradually begins to resemble those of the adult. Once
the adult microbiota is established, by the age of about
2–3 years, it is relatively stable within an individual but
nevertheless subject to influence by diet, disease, use of
medication (particularly antibiotics) and ageing.
Gut microbes may be commensal (a person’s native,
colonising microbes) or transient (microbes just passing
through). Furthermore, these microbes can be beneficial,
potentially harmful or pathogenic. Microbes considered
to be beneficial usually ferment carbohydrates, do not
produce toxins and may have a range of potential benefits stable microbiota but there is considerable inter-individual
for the host such as interaction with the immune system variation.
and competitive inhibition of pathogens. Such microbes
Deviations in composition or function from the usual
include Bifidobacterium, Eubacterium and Lactobacillus.
microbiota, known as dysbiosis, have been observed in
The small intestine is the main target of many exogenous certain disease states (Table 1) but it is not known whether
infections such as rotavirus, Salmonella typhimurium and the change in the microbiota causes, or partly causes,
some Escherichia coli types, which are usually contracted the disease state or whether the change in microbes is a
from contaminated water or foods. However, all individuals result of the disease itself. Changes in the microbiota can
harbour microbes that have opportunistic, pathogenic certainly result from a GI infection or use of oral antibiotics
potential. Amongst the most important of these is to treat a disease, but such alterations are usually quite
Clostridium difficile, which may become prominent and rapidly corrected without intervention and the microbiota
cause serious diarrhoea and inflammation when conditions returns to “normal” for that individual. However, repeated
in the gut are altered by illness or medication. C. difficile antibiotic use may result in permanently disrupted
often becomes a transmittable pathogen through microbiota. Whether or not prebiotics and probiotics
contamination of food or surfaces, especially in hospitals can hasten or improve the correction of the microbiota
or care homes. Other undesirable colonic microbes such following an insult is a subject of research.
as peptolytic bacteria and sulphate-reducing bacteria do
not cause acute disease but can be associated with the
production of toxins, pre-carcinogens, carcinogens and
TABLE 1.
toxic gases (such as hydrogen sulphide). In turn, this may Disease states that have been associated with altered
result in the host becoming more susceptible to transient GI microbiota (adapted from Sanders, 2011)
pathogens, antibiotic-associated diarrhoea and, possibly,
inflammatory bowel disease and irritable bowel syndrome. Atopy (allergy) and asthma
Probiotics are transient, although some may belong to Coeliac disease
species that are also normal commensal organisms. Some, Colon cancer
but not all, probiotics are able to replicate and persist in the
Type I diabetes
gut at least temporarily, but they disappear a few days after
cessation of their intake. Type II diabetes
HIV infection
Although recent research has provided a great deal
of information about the overall composition of the Inflammatory bowel disease (IBD)
gut microbiota, there is little certain knowledge about Irritable bowel syndrome (IBS)
what constitutes the normal microbial composition GI infections
(eubiosis) of the gut. In part, this is because it is difficult
Antibiotic-associated diarrhoea (AAD)
to study what is happening inside the GI tract of a healthy
individual. Hence, there is no definition of the “normal” Necrotising enterocolitis
or “healthy” microbiota, although this is a key objective Obesity
of current research. Individuals may have a reasonably Rheumatoid arthritis
Recent research also suggests that the normal microbiota activity that is harnessed by humans in the production of
is not simply a collection of micro-organisms, but reflects an various food products. For example, in wine production,
inter-relationship between different groups that may work yeast ferments the sugars in grape juice to yield alcohol.
together to the benefit of the host. In addition, the current In yogurt production, bacteria such as lactobacilli and
thinking is that harbouring a wide diversity of organisms in streptococci ferment milk sugar (lactose) to lactic acid
the GI tract is beneficial to the host. to develop the characteristic tart flavour. In sauerkraut
production, the bacteria naturally present in cabbage
ferment sugars to lactic acid in the absence of oxygen
Bacterial fermentation and and the presence of 2-3% salt.
metabolism In like manner, microbes in the first part of the colon meet
As living organisms, all microbes require a source of their energy needs by fermenting dietary and endogenous
energy in order to grow and reproduce. Many microbes residues that have escaped digestion and absorption in
ferment carbohydrates (saccharolytic fermentation), an the upper GI tract (Table 2 and Figure 2). Many microbes
TABLE 2.
Bacteria, their mode of action on substrates and the products of fermentation (adapted from Salminen, 1998)
Bacteria Mode of action on substrates Fermentation products

Bacteroides Saccharolytic, peptolytic, aa-fermenting Ac, Pr, Su, Am
Eubacteria Saccharolytic, some aa-fermenting species Ac, Bu, La, Am, Sul
Bifidobacteria Saccharolytic Ac, La, f, EtOH
Ruminococci Saccharolytic Ac
Peptostreptococci Saccharolytic, some aa-fermenting species Ac, La, Am
Peptococci aa-fermentation Ac, Bu, La, Am
Clostridia Saccharolytic, some aa-fermenting species Ac, Pr, Bu, La, EtOH, Am, Sul
Lactobacilli Saccharolytic La
Propionibacteria Saccaharolytic, lactate fermentation Ac, Pr, Am
Actinomyces Saccharolytic Ac, Pr
Streptococci Carbohydrate and aa-fermentation La, Ac, Am, Sul
Methanobrevibacter Chemolithotrophic CH4
Escherichia Carbohydrate and aa-fermentation Mixed acids, Am
Desulfovibrio Various Ac, Sul
Fusobacteria aa-fermentation, assimilation of carbohydrates Bu, Ac, La, Am, Sul
aa, amino acid; Ac, acetate; Am, amines; Bu, butyrate; EtOH, ethanol; f, formate; La, lactate; Pr, propionate; Su, succinate; Sul, sulphides
FIGURE 2.
Diagram showing the principle metabolic activity in the colon
Source: Prof. R. Rastall, University of Reading, UK
metabolise carbohydrates and dietary fibre1, including of the fermentation products depends partly on the
polysaccharides (such as pectins, hemicelluloses, gums, substrate fermented and the type of bacteria (Table 2) and
inulin and resistant starches), oligosaccharides (such as also on other individual host factors. SCFA are absorbed,
raffinose, stachyose, fructo-oligosaccharides, galacto- enhancing the uptake of water and salts, and are used as a
oligosaccharides and resistant dextrins), sugars (lactulose, source of energy by the host. Butyric acid is also the major
non-absorbed lactose and non-absorbed fructose) and source of energy of the epithelial cells lining the colon and
polyols (such as mannitol, lactitol, maltitol and isomalt). can impact cell growth and differentiation.
The main species in the colonic microbiota that ferment
The gases hydrogen, methane and carbon dioxide are also
carbohydrates belong to the genera Bacteroides,
produced and may contribute to the equilibrium of the
Bifidobacterium, Ruminococcus, Eubacterium and
microbiota. In addition, these gases can cause flatulence
Lactobacillus. This microbial action results in the production
and distension, which can lead to intestinal discomfort if
of the short chain fatty acids (SCFA) acetic, propionic and
the dietary intake of fermentable substrates is suddenly
butyric acids and of lactic acid (which is mostly converted
increased.
to acetic and propionic acid by gut microbes). The nature
1. Note that the legal definition of dietary fibre differs around the world. The term dietary fibre is used here only in a general sense to refer to the
dietary components listed.
Bacteria also metabolise other components found in At birth, the GI tract is essentially sterile and, in addition, the
their environment (Figure 2). In addition to foodstuffs newborn’s immune system is not fully mature. The immune
consumed by the host and not fully digested, substrates system only becomes functionally mature as a result of
for bacterial growth include degraded bacterial cells and exposure to the myriad of foreign substances encountered
host-derived mucins, enzymes and sloughed-off intestinal by the naive intestinal tract. Studies on animals raised in
cells. Peptococci and clostridia species metabolise proteins germ-free conditions have shown that the immune system
as a source of nitrogen for growth and yield branched is poorly developed in such animals and that they have
chain fatty acids such as isobutyrate and isovalerate as lower levels of immunoglobulins and fewer specialised
well as a range of nitrogenous and sulphur-containing immune cells in their intestinal mucosa. Germ-free animals
compounds, some of which may be harmful. For example, are thus much more susceptible to disease than are those
ammonia, amines and phenolic compounds can, under that are conventionally reared. It is also known from these
certain conditions, lead to the formation of carcinogens, studies that microbial antigens, derived from the intestinal
particularly in the left, descending colon where putrefactive microbiota as well as the environment, play a crucial role in
conditions can prevail. Phytochemicals such as isoflavones the maturation of gut-associated lymphoid tissue (GALT)
and polyphenols may also be metabolised, yielding smaller and normal resistance to disease.
components like equol and small phenolic molecules that
The GALT is organised into different compartments such
are more readily absorbed. The impact of this microbial
as lymph nodes, lymph follicles and Peyer’s patches
activity on human health is still under investigation.
(Figure 3). The GALT limits the passage of bacteria
As bacteria grow in numbers, they contribute to the bulk and food antigens from the GI lumen through the
of the stools that form in the rectum. High stool bulk is intestinal mucosa. It does, however, allow the passage
related to a shorter gut transit time and also to a lower of antigens (minute samples of viable or dead bacteria
risk of constipation and bowel cancer. Although non- and protein and peptide fragments) using specialised
fermentable dietary fibre sources such as wheat bran fibre cells such as the M cells that cover the Peyer’s patches
are the most important contributors to stool bulk, bacterial and the dendritic cells that act as sentinels along the
mass resulting from the fermentation of more soluble mucosa. These so-called antigen-presenting cells (APCs)
dietary fibres and carbohydrate residues also contributes process and present the antigens to lymphocytes, a
to the bulk. type of immune cell. The APCs are thus very important
in stimulating a balanced immune response and, as is
increasingly documented, having an impact beyond the
The GI epithelial barrier and immune gut (see the section “Cross-talk with the host”). It has
been hypothesised that reduced exposure to exogenous
system microbes in developed and industrialised countries has
The GI tract is sometimes described as the body’s largest led to increased incidence of chronic immune dysfunction,
immune organ. It represents the host’s greatest area leading to atopic (allergic) and auto-immune disorders or
of mucosal contact with the environment and contains inflammatory bowel disease, because of changes in the
as many as 80% of all antibody-producing cells. The way the immune system has matured. This is known as
intestinal microbiota is also a vital part of the body’s the “hygiene hypothesis”.
defence system.
FIGURE 3.
Schematic overview of the lymphoid elements of the gut-associated lymphatic system
Peyer’s patches (PP) and mesenteric lymph nodes (MLN) are organised intestinal lymphoid follicles. (A–C) Pathways of intestinal antigen uptake:
luminal antigen can be taken up by (A) intestinal epithelial cells, (B) interdigitating lamina propria dendritic cells, and (C) M cells. The lymphatic
drainage of PP and villus lamina propria goes to the MLNs (direction of lymph flow is indicated by arrows). Reproduced from Spahn and Kucharzik
(2004) with permission from BMJ Publishing Group Ltd.
The integrity of the epithelial lining of the GI tract is crucial mobile layer of mucus whereas the colon has two layers:
to health and the disruption of this intestinal barrier may a mobile layer similar to that of the small intestine and
increase the risk of certain intestinal disorders or diseases. a second thinner layer that is much more viscous and
Epithelial cells have become specialised and adopt a impermeable than the mobile mucous layer. Although
number of strategies for defence against pathogens. microbes reside predominantly in the lumen of the GI
tract, they are also associated with the mucous layer
Goblet cells secrete mucins (high molecular weight
and may adhere to the cells lining certain areas of the
glycoproteins), which act as a layer that helps protect
small intestine if the mucous layer is compromised. Here,
the underlying epithelial cells from mechanical damage
beneficial microbes may compete with pathogens.
and the direct action of chemical compounds that are
ingested or derived endogenously from gut secretions. Both the mucous layer and the epithelial cells are designed
The amount and composition of mucus produced by the to allow selected nutrients and other dietary components
gut varies by site. The small intestine has a thick, quite to penetrate and, in some cases, pass through them.
In addition, some components pass through the inter- In the early 1990s, research scientists developed a
cellular spaces. Proteins known as occludins and claudins technique called fluorescence in situ hybridisation (FISH).
help police the small intercellular space (tight junction) By using fluorescent probes directed to highly variable
between cells to control access by foreign molecules and regions of the 16S ribosomal ribonucleic acid (rRNA)
particles. within the bacterial cells, different species and even sub-
species of bacteria could be identified and quantified.
Specialised Paneth cells, located in the crypts of the
From the mid-1990s, sequence analysis of 16S ribosomal
small intestine, produce antibacterial peptides known as
DNA, often obtained by polymerase chain reaction
defensins as well as defensive enzymes (such as lysozyme)
(PCR), was possible, which enabled microbiologists to
and cytokines that help protect the host from pathogenic
detect and identify micro-organisms without the need
micro-organisms.
to culture them. Simultaneously, sequence analysis
revealed a far greater diversity than previously detected
Techniques for exploring the GI by culturing. These techniques have allowed more
accurate detection and identification of specific species,
microbiota especially ones that were previously unknown or difficult
In the past, microbes taken from their initial source to culture, from faecal or intestinal samples. Culture-
(whether food, blood, tissue or excreta) were independent analysis of faecal samples has thus led to
characterised after culturing them in a laboratory. The an increased understanding of the complexity of the
cultured micro-organisms could then be counted and intestinal microbiota. Modern techniques also allow very
identified by microscopy, biochemical observation and high numbers of samples to be analysed in parallel and
other taxonomical (identification) tests (see section thus have increased the knowledge of inter-individual
“Characterisation and taxonomy” for information on variation and stability of the microbiota within individuals.
taxonomy).
The co-development of high-throughput DNA
Faecal sampling has always been the mainstay of analysis sequencing technology and information technology (bio-
of the human gut microbiota, especially given the limited informatics) has enabled clustering and analysis of large
accessibility of other GI sites. An inherent limitation of amounts of data such that researchers have embarked
this approach is that the micro-organisms expelled in the upon major new projects to study the human microbiome
faeces and cultured in the laboratory do not necessarily – a term that refers to the collective genomes of all
accurately reflect what can be found in different segments micro-organisms present in an ecosystem, in this case,
of the gut, particularly the upper gut. Even colonic biopsy the human body. The Human Microbiome Project (USA-
samples may not accurately reflect the in vivo situation led) and the MetaHIT project (Europe-led) comprise
because, prior to their excision, the colon is cleared with large research consortia that have started to study and
laxatives, which disturbs the endogenous microbiota. characterise the complete microbial population of the
Another challenge in understanding the composition of human intestine and other parts of the body, with the
the gut microbiota is that numerous microbes have not yet aim of associating the composition and function of
been successfully cultivated under laboratory conditions. the microbiome with health and disease. A great deal
of current research on probiotics and prebiotics also

interfaces with these ongoing research programmes
THE PROBIOTIC CONCEPT
on commensal bacteria. All these projects will help to
shed light on the role of microbes, both commensal and
ingested, in human health.
Definition and history
Analysis of the intestinal microbiota has made tremendous
progress, in particular in the past two decades with the The word “probiotic” (origins: Latin pro meaning “for”
mainstream use of various molecular techniques. These and Greek bios meaning “life”) was first used in 1954
techniques have made it possible to both investigate to indicate substances that were required for a healthy
the unknown members of the microbiota and their life. Out of a number of definitions, the most widely used
functionality as well as follow specific strains. A number and accepted definition is that proposed by a joint FAO/
of challenges remain, however. Analysis primarily remains WHO panel (FAO/WHO, 2001): “Live micro-organisms
restricted to faecal samples that may not be representative which, when administered in adequate amounts, confer
of the microbiota higher up the GI tract or the microbiota a health benefit on the host”.
associated with the mucosal surfaces. On the analytical As mentioned, the original proposal that certain bacteria
side, new techniques allow the accurate and quantitative could benefit human health is usually attributed to Ilya
analysis of the microbiota and, although the detection Metchnikoff, who worked at the Pasteur Institute at the
limits may currently still be too high to capture all the minor beginning of the twentieth century. His insights still have
components of the intestinal microbiota, it is reasonable resonance today:
to assume this will improve in the future. More powerful
computers and new statistical algorithms will also be “The dependence of the intestinal microbes on the
required to deal with the ever-increasing amount of data. food makes it possible to adopt measures to modify the
flora in our bodies and to replace the harmful microbes
by useful microbes” and “systematic investigations
should be made on the relation of gut microbes to
precocious old age, and on the influence of diets which
prevent intestinal putrefaction in prolonging life and
maintaining the forces of the body.”
A French paediatrician, Henry Tissier, also published
information at around the same time about his work on
young children with diarrhoea. He found that their stools
contained fewer unusual Y-shaped (“bifid”) bacteria
than did stools from their healthy peers and suggested
that patients with diarrhoea could be treated with these
“bifid” bacteria to help restore a healthy gut microbiota.
Until recently, high quality scientific research supporting
the purported benefits of probiotics was limited, partly
because the complexity of the gut ecosystem was largely Characterisation and taxonomy
underestimated. In the last three decades, research
has progressed and, with the application of molecular The determination of genus, species and strain is essential
techniques, major advances have been made in the for full characterisation of a microbe.
characterisation of specific probiotics as well as in our Taxonomy provides a first view of the organism’s main
understanding of their mechanisms of action and health physiological and metabolic properties, indicates
effects. whether there are any potential safety concerns, and
allows discrimination between individual strains. Indeed,
full characterisation of probiotics is a requirement for
Selection of probiotic candidates evaluation of a health claim in Europe.
Beyond safety, the selection of a probiotic strain is
driven primarily by its potential to confer a health benefit FIGURE 4.
for humans. It is commonly considered that, for food
Code of Nomenclature, showing Lactobacillus
applications, probiotics need to survive until they reach
acidophilus as an example
the part of the GI tract where they exert their intended
effect. For example, to be active in the colon, probiotics
must resist salivary enzymes, stomach acid, small intestinal
secretions of bile and enzymes as well as the pH changes
and chemical milieu of other foods and beverages they Bacteria
will encounter during their passage along the GI tract.
In addition, they need to compete with the resident Eubacteria
microbiota. Finally, a selected strain has to fulfil a number
of technological requirements, such as culturability on a Firmicutes
large scale, genetic stability and maintaining viability in a
food product or supplement. Thus, the identification of Bacilli
suitable probiotic strains worthy of further study is a very
complex and detailed process that can take substantial
Lactobacillales
research effort.
The most commonly used probiotics in foods are species Lactobacillaceae
from the genera Lactobacillus and Bifidobacterium,
but yeasts such as Saccharomyces spp. have also been Lactobacillus
used. There are a number of important steps required to
characterise each strain. acidophilus
Strain xx
FIGURE 5.
Representation of genomic commonalities and differences for three strains belonging to the same species
Species X
Strain A Strain B
Genes common
to all
three strains
Strain C
Modern molecular methods should be used for species Safety

and strain identification because they are far more reliable
than phenotypic methods. Thanks to recent progress in Many probiotic organisms belong to genera represented
technology, sequencing the full genome of a new strain in the functional group of bacteria known as lactic acid
is no longer very expensive or time-consuming and this bacteria, which have been safely consumed for many
opens the way for detailed characterisation of a specific years and as such are presumed to be safe ingredients
strain and comparison with its close relatives. There is in the food supply. To formalise and underwrite this
an International Code of Nomenclature that has to be concept, a system for a pre-market safety assessment
followed in naming all micro-organisms (Figure 4). was proposed that leads to a ‘Qualified Presumption of
Safety (QPS)’ in the European Community. In summary, a
Through assessing phenotypic and genotypic properties, safety assessment of selected groups of micro-organisms
microbial taxonomy groups together related species into from a defined taxonomic group (e.g. genus or group of
one genus and, further, related strains into one species. related species) can be made on the basis of four pillars
Nevertheless, even when belonging to the same species, of information (identity, body of knowledge, possible
different strains can be distinguished by unique genetic pathogenicity and end use). If the taxonomic group and
and physiological properties (Figure 5). characterisation to strain level do not raise safety concerns
or if any safety concerns can be defined and excluded,

the organism may be granted QPS status. Thus, for
THE PREBIOTIC CONCEPT
any strain of micro-organism that can be unequivocally
demonstrated to be from a qualified QPS group (such
as Lactobacillus or Bifidobacterium), further safety
assessment is limited to tests for antibiotic resistance. If Definition and history
a microbe is not covered by QPS, then a comprehensive As mentioned, the Japanese were the first to recognise the
assessment of safety is likely to be required before it can value of fermentable oligosaccharides, initially in feeding
be used in the food supply. piglets and later, during the 1980s, with the identification
of human milk oligosaccharides. However, it was not
until 1995 that the prebiotic concept for modulation of
Application of probiotics in food gut microbiota was introduced. Although a number of
Probiotic organisms are used in a variety of foods, the definitions have been proposed, there is as yet no full
main category being dairy products, but they are also agreement on a single definition of a prebiotic. The most
present as food supplements in capsule or tablet form. recent was agreed at the 2010 Meeting of the International
Since viability is an essential property of a probiotic, the Scientific Association of Probiotics and Prebiotics (ISAPP)
final product must contain an adequate amount of living (Gibson et al., 2011):
probiotic(s) until the end of its shelf life. A health claim for “A dietary prebiotic is a selectively fermented ingredient
the addition of probiotics to foods or food supplements that results in specific changes, in the composition
should only be made if there are documented benefits and/or activity of the gastrointestinal microbiota, thus
based on good quality human trials conducted with the conferring benefit(s) upon host health.”
relevant food product containing the specific strain that
is the subject of the claim and using relevant endpoints.
These studies should also be able to demonstrate the
safe, effective dose of the probiotic organism in food.
Characterisation of prebiotic
Like legislation on food safety, regulation of health claims ingredients
for foods varies by country or region and any claims on Although not stipulated as a requirement in the definition
commercial products containing probiotics must adhere of a prebiotic, to date only carbohydrate compounds
to requirements, which in some cases include pre-market have been studied with regard to prebiotic activity.
approval of the claim by the regulatory authorities. Most research has been carried out on fructans (i.e. the
polysaccharide inulin or fructo-oligosaccharides (FOS)
derived from various crops or from sucrose) and galacto-
oligosaccharides (GOS). For these ingredients, selective
fermentation and a shift in the microbiota have been
confirmed in human studies and they have been linked
to potential health benefits. Candidate or emerging
prebiotics require additional evidence in humans before
they can be fully established as prebiotic. Such candidate
prebiotics include the disaccharide lactulose, further intake in order to establish prebiotic status. Furthermore,
oligosaccharides and resistant dextrins, polysaccharides human feeding trials are essential in order to demonstrate
such as polydextrose, arabinoxylans and resistant starches a health benefit.
as well as some polyols such as lactitol and isomalt.
The main site of action for prebiotics is the colon. Thus,
Some prebiotics occur naturally in foods such as chicory, a prebiotic should resist the effects of gastric acidity and
cereals, agave and milk. However, most foods contain digestive enzymes in order to reach the colon intact. Once
only trace levels, so the approach of refining the active there, prebiotics confer their purported benefits through
ingredients from these foods crops or of producing the stimulation of the growth and/or the metabolic
them by synthesis (e.g. enzymatic, chemical or thermal activities of the bacteria that ferment them. The foremost
processes) has been undertaken in order to attain levels in target genera for prebiotic action are bifidobacteria and
foods whereby a prebiotic effect may occur. lactobacilli, although this may change as knowledge of
the microbial diversity and functionality expands. It can,
Many prebiotics and candidate prebiotics today fall into
however, not be excluded that prebiotics have a direct
the nutritional and regulatory definition of dietary fibre and
effect on health e.g. through the immune system or an
are labelled as nutrients of that category. They share with
impact on binding of microbes to receptors.
dietary fibre the properties of resistance to digestion and
(for some fibres) fermentability, but established prebiotics Prebiotics and probiotics may be combined into
are distinguished from dietary fibre by the selectivity of “synbiotics”. In this case, the effects of the two components
their fermentation. Note that mono- and disaccharides are should be synergistic. The probiotic may be stimulated to
typically not considered as dietary fibre according to EU grow in the gut by fermenting the prebiotic and/or the
and CODEX definitions. prebiotic may support a more favourable gut environment
in which the probiotic may better compete.
Criteria for prebiotic selection

Prebiotics have an action complementary to, but distinct Application of prebiotics in food
from, probiotics. Probiotics are exogenous micro-organisms
As noted above some prebiotics or candidate prebiotics
that are ingested to promote a specific health effect. In
are naturally occurring and widely consumed at low levels
contrast, the prebiotic concept is based on the selective
in the normal diet. The commercial prebiotic ingredients
stimulation of the host’s own beneficial microbiota, the
GOS and fructans are used in infant foods when their safety
prebiotic being the substrate that is (selectively) fermented,
and efficacy has been demonstrated; in some countries
stimulating the growth and activity of the particular micro-
this may require premarket approval. In foods for general
organism or group of micro-organisms of interest and thus
consumption, the target level of intake of prebiotic ranges
leading to the desired health effect.
from 2 to 20 g per day, depending on the ingredient
It is essential to measure the effect of the candidate and the desired effect. These amounts can be readily
prebiotic on bacterial growth; it is not enough simply incorporated into a variety of foods such as cereals, bread,
to know that fermentation has taken place. Although in confectionery, biscuits, yoghurts, table spreads, sauces
vitro tests can be used to screen potential candidates, the and drinks. Similarly to the case of probiotics, the health
increase in target microbes must be quantified in human benefits of candidate prebiotics need to be demonstrated
trials after a short feeding period at acceptable levels of in clinical trials.
HEALTH EFFECTS response to a vaccine or reduction in the duration of

validated symptoms are still more widely accepted as
OF PREBIOTICS AND evidence of benefit than are changes in a biomarker.
PROBIOTICS Another challenge that is common to all research in humans
is inter-individual variation, i.e. the variability in results
observed for a specific endpoint in different subjects. Inter-
Research challenges individual variability depends on a wide range of factors
In order to demonstrate that probiotics and prebiotics including host genetics, diet, microbiota, age, nutritional
have beneficial effects on human health, evidence should status and other lifestyle factors. Researchers try to control
be provided by nutritional intervention studies in human for these differences but must include sufficient subject
subjects. Supportive evidence may be gathered from numbers to allow for variation. In addition, the effects of
animal feeding studies (in vivo studies) as well as from an intervention may be more evident in people at high risk
laboratory studies that examine blood or tissue samples of, or diagnosed with, a disease than they are in healthy
taken from humans or animals (ex vivo studies), or by subjects. This often poses a question as to whether the
examining isolated cells that are grown in culture in the effect would be observed in healthy people.
laboratory and subject to various experimental conditions In all cases, it is clear that prebiotics and probiotics must
(in vitro studies). These non-human studies can provide be consumed regularly in order to confer a benefit.
insights into mechanisms of action, but are not suitable
per se to substantiate a human health benefit.
Impact on the GI tract of prebiotics
One of the factors that has hampered progress in research
into the health impact of functional foods, including and probiotics
probiotics and prebiotics, is the lack of generally accepted Gut microbiota
biomarkers of GI health and immune function. In this
An increased proportion of bifidobacteria and lactobacilli is
context, biomarkers are surrogate markers of health
thought to represent a “healthier” microbial composition.
endpoints just as blood cholesterol level is a well-accepted
This is partly based on evidence from infants, which is
risk factor of disease. Accepted markers of GI function
discussed later in this section as well as in the section on
include stool bulk and the transit time through the GI
mechanisms. These bacteria are more likely to ferment
tract, and these can be used to demonstrate the benefit
carbohydrates and produce acids, and they generally lack
of prebiotics and probiotics. There are numerous markers
potential toxicity.
used in relation to the immune system but knowledge is
lacking about the predictive value of single markers of There is ample evidence in human subjects, including
function, such as immune cell function, cytokine levels, infants, as well as in animal and in vitro studies that
or antibody production, in overall immune health. The established prebiotics increase the proportion of
relevance of these immune markers remains to be bifidobacteria and sometimes lactobacilli present in the
established, even when more than one marker is used. The gut microbiota while having no measurable effects on
absence of agreed markers means that clinical endpoints other groups of bacteria.
such as reduced susceptibility to an infection, enhanced
In the case of probiotics, the consumption of adequate intestinal discomfort, such as bloating, abdominal pain
doses of Lactobacillus strains often results in a measurable and flatulence. Studies on certain strains of probiotic
increase in the lactobacilli in the faeces, and in some bacteria have demonstrated an impact on gut function,
cases there may be a decrease in unfavourable organisms as revealed by normalisation of transit time and reduction
such as staphylococci. For pre-term infants, who usually of self-reported minor digestive discomfort symptoms.
harbour reduced numbers of bifidobacteria, there is An improved transit time may reduce putrefactive activity
good evidence that the ingestion of bifidobacteria not in the left colon, as indicated by some studies that have
only increases their numbers but may also reduce the found reduced levels of polyamines and metabolites
numbers of clostridia. In practice, the effect of prebiotics such as cresol and indoles.
and probiotics on the microbiota is somewhat variable
These stool-regulating effects are considered to be
but also difficult to measure because of the factors
beneficial to gut health by decreasing the risk of
discussed in the section “Techniques for exploring the
constipation. An improvement of stool function is likely to
GI microbiota”.
be important with respect to the general population since
In addition to considering an increase in the number or dietary fibre intakes in developed countries are almost
proportion of certain microbes, it is also important to universally lower than recommended and the number of
consider their functional capacity, which may be changed people reporting digestive problems is extremely high
by prebiotic or probiotic consumption in the absence of (more than 80% in some surveys of women). As with
an alteration in number or proportion. Recent human all dietary fibre, too-high an intake of prebiotics may
data on probiotics using new techniques have enabled need to be avoided by certain individuals because over-
measures of components that reflect the genes that consumption could lead to bloating and, in severe cases,
are being actively expressed at any given time. The link to watery stools. However, this subsides if consumption
between gene expression and health outcomes will no is reduced or stopped.
doubt be the subject of future research.
Chronic inflammatory gut conditions
Transit time and stool bulking The inflammatory bowel diseases (IBD) are serious
There is strong evidence that prebiotics and probiotics conditions with an as-yet unknown cause. They include
can influence gut function. This effect for prebiotics is Crohn’s disease (CD), which can affect the whole gut
thought to be due to their fermentation in the colon, though mainly affects the small intestine, and ulcerative
resulting in increased bacterial mass and osmotic water- colitis (UC), which is usually restricted to the large bowel.
binding capacity that contribute to increased stool IBD is associated with a breakdown of the normal barrier
weight, increased stool frequency and softer stools. function provided by the gut epithelial lining and its
There is also some evidence that SCFA, especially associated mucus. Whether the inflammation causes the
butyrate, have a positive effect on the endothelium breakdown of the barrier or if a breakdown of the barrier
and on peristalsis, which improves transit. Because allows inflammation to develop is not clear. It is known
there is an inverse link between stool mass and transit from studies on germ-free animals compared to normal
time, prebiotics may also decrease transit time. In some animals that germ-free animals are less susceptible to
studies, prebiotics are reported to reduce symptoms of experimental IBD and that the presence of commensal
bacteria can initiate and/or exacerbate inflammatory a potential cause of IBS. In addition, in a certain subset of
bowel conditions. CD and UC may thus result from an subjects, it appears that previous gut infections play a role
inappropriate mucosal immune response to the GI in onset of IBS (post-infectious IBS). Furthermore, in some
microbiota in genetically susceptible individuals. There is studies, lower levels of bifidobacteria have been observed
also some evidence from clinical studies that the balance in subjects with IBS compared with healthy subjects.
of different groups of commensal bacteria might be
Because of the lack of good therapy for IBS and the
altered in IBD patients.
identification of abnormal microbiota in IBS subjects, both
Numerous studies of both probiotics and prebiotics probiotics and prebiotics have been investigated for their
in animal models have shown a positive impact on the ability to help subjects manage this condition. A couple
prevention or treatment of IBD. Clinical studies in CD of probiotic preparations have been shown to provide
subjects have not been effective in prolonging remission reduction in a global symptom score (the sum of a number
of CD, but there are promising data indicating that of different symptom scores) and in reducing abdominal
some probiotics are useful in maintaining remission in pain; however, no change in diarrhoea, constipation or
UC. In another inflammatory bowel condition known as bloating was confirmed. In other studies, some strains
pouchitis, which can occur after surgery to treat UC, one had no effect or resulted in worsening of symptoms. For
mixture of probiotic strains appeared to be effective in some prebiotics, studies showed that low doses led to
helping maintain remission. The potential for prebiotics an improvement in the condition, whereas a larger load
and synbiotics to help the management of IBD has been led to an enhancement of the perceived symptoms.
shown in several small studies with fructans, mainly in the Thus, additional research will be required to determine if
reduction of inflammatory markers, but as yet the data consistent benefits can be observed by those experiencing
do not allow a final conclusion. Although there are still IBS if they use prebiotics and probiotics.
insufficient data to draw firm conclusions on the effect of
pre- or probiotics on IBD, importantly, none of the trials
conducted thus far have raised concerns regarding their Impact on the GI tract specific to
safety in patients with IBD at the levels of intake tested. prebiotics
Irritable bowel syndrome Colon cancer
Irritable bowel syndrome (IBS) is a distressing condition Colon cancer has been linked to diets low in dietary fibre
that is characterised by an array of symptoms such as and thus the potential for prebiotics to reduce colon
abdominal pain, bloating and altered bowel habits that cancer risk has also been investigated, mainly using
may often alternate between constipation and diarrhoea. in vitro techniques and animal models. Results from
As similar symptoms can be observed from time to time in animal studies with endpoints such as DNA damage,
the general population, a specific set of criteria (known as aberrant crypt foci as well as tumours in the colon
the Rome criteria) was developed to improve consistency suggest that prebiotics may reduce the risk of colon
of diagnosis of IBS. In industrialised countries, IBS affects cancer. This is supported by ample in vitro evidence.
between about 5 and 20% of the adult population, with Synbiotics were investigated in a few animal studies and
rates higher in women and older people. Recently, there were found to be more effective than either prebiotics
has been interest in the role of inflammatory processes as or probiotics alone. One synbiotic study (SYNCAN
project) in humans found a reduction in DNA damage mineral absorption is available from pigs, which are
and a reduction in cell proliferation in colon biopsies. considered a better model for the human than are rodents.
Potential mechanisms for a prebiotic effect on colon Numerous human intervention studies consistently show
cancer risk have been identified in animal studies and an increase in calcium absorption. So far, there is one
include changes in gut bacterial enzyme activities, which long-term human intervention study that assessed the
modify the fermentation products, and up-regulation of effects of prebiotics on bone health. The study was in
apoptosis (programmed cell death – in this case of the adolescents and used a combination of FOS and long-
pre-cancerous cells). However, definitive evidence that chain inulin (50/50). After one year, bone mineral density
certain prebiotics might reduce the risk of colon cancer and bone mineral content were significantly higher at
in human subjects is lacking and requires more robust, certain bone sites in the supplemented group. Whether
multi-centre, prospective human trials. this effect is common to all prebiotics or unique to the
particular formulation requires further substance-specific
Prebiotics in early life nutrition research.
Oligosaccharides with fucosyl, galactosyl and sialyl Gut hormones and food intake
structures are found in human breast milk and are
thought to promote healthy microbiota. Intervention Numerous studies in rodents, mainly with fructans,
studies show that infant formula supplemented with GOS show a consistent effect of feeding prebiotic fibres in
and fructans, alone or in combination, help stimulate the reducing food intake and decreasing fat mass, though
bifidobacteria that are characteristic of breast-fed infants not necessarily body weight. Additional data from these
in a dose-dependent manner. Further, infants fed formula studies suggests that the mechanism for this is likely
with oligosaccharides have microbiota, a stool pH and a to be SCFA-stimulated secretion of gut peptides such
SCFA pattern similar to those of breast-fed infants. The as glucagon-like peptide (GLP)-1, peptide YY (PYY)
stool consistency and stool frequency of prebiotic-fed and oxytomodulin and reduced secretion of ghrelin,
infants (softer and more frequent) is also closer to that all of which are secreted by endocrine-type cells in
seen for breast-fed infants than for those fed standard the mucosa. These peptides are known to affect food
formula. The use of specific GOS and fructan prebiotics intake in animals and humans. Overall, evidence from
in infant formula is widespread practice and accepted an increasing number of studies in human subjects,
as safe. The range of the resulting benefits of these mainly with fructans, supports an effect of daily prebiotic
prebiotics as well as of other prebiotic candidates is still consumption in reducing appetite, lowering body weight
an active area of research by experts in the field. or fat mass, altering gut peptide levels in blood and
improving glucose tolerance. Some, but not all, of these
Mineral absorption studies examined the composition of the gut microbiota;
One specific, well-established effect of prebiotics is on where examined, shifts in the microbiota were confirmed.
mineral absorption. There is a wealth of data showing The impact of SCFA on glucose and lipid metabolism
that prebiotics increase calcium absorption and increase may also be important.
growth and skeletal mass in rats. In addition, there
are some studies showing enhanced absorption of
magnesium and iron. Further evidence for an improved
Impact on the GI tract specific to with evidence from mechanistic studies showing changes
in certain immune parameters, support the notion that
probiotics the effect of probiotics and prebiotics on the immune
Lactose malabsorption system can translate into measurable health benefits, but
definitive evidence is lacking.
As discussed in the section on “Bacterial fermentation
and metabolism”, many micro-organisms ferment Gastrointestinal infection
lactose, the sugar found in milk and products made from
The small intestine is the main target of many GI
milk. Although infants rely on lactose, which contributes
infections such as rotavirus, S. typhimurium and some
as much as 10% of the energy in breast milk, many
E. coli types. As early as 1916, it was reported that
populations around the world have a high proportion of
S. typhimurium was cleared from the GI tract of healthy
adults who are unable to digest this sugar. In humans, and
carriers of the organism when members of the normal
in fact in all mammals, expression of the enzyme lactase
gut microbiota were introduced. Probiotics have long
is down-regulated in adulthood with the exception of
been associated with a purported ability to counteract
some population groups, particularly those of European
pathogenic bacteria and so recently several potentially
origin. Lactose intolerance is a condition in which the
beneficial strains have been tested in controlled studies.
colonic fermentation of undigested lactose results in
gastrointestinal effects such as abdominal pain, bloating, The first-line of treatment for the symptoms of diarrhoea
borborygmi or laxation. There is evidence that the live is oral rehydration – and no other dietary treatment
bacteria of yogurt are able to compensate for the lack should be substituted for this, especially in infants.
of endogenous lactase in the human gut by digesting However, in established conditions, some probiotics
lactose. The typical measure of improved lactose can be used as an adjunct under medical supervision
digestion is a reduction in breath hydrogen excretion where appropriate. Certain probiotics seem to be most
(breath hydrogen is usually raised when undigested effective in improving symptoms when the diarrhoea is
carbohydrate reaches the colon and is fermented). This the result of a viral (rather than bacterial) infection, if they
improved digestibility reduces the symptoms related to are used early in the course of the infection and are given
lactose intolerance in some lactose malabsorbers. in sufficient amounts. In terms of reduced susceptibility
to infection, some studies have found decreases in the
risk of infection in infants (mainly in developing countries)
Impact on the immune responses and in institutionalised or hospitalised elderly. Efficacy
is clearly strain related, i.e. some strains are effective
Germ-free animals have, as mentioned, an
and others not. In addition, there is some evidence that
underdeveloped immune system and GI epithelium,
specific probiotic strains, and some prebiotics, may
resulting in reduced resistance to infection compared
reduce the risk of traveller’s diarrhoea.
with conventional animals. It is thus accepted that
commensal organisms are vital for the maturation of Some antibiotics can significantly disrupt commensal
the immune system. The potential for probiotics and bacteria, resulting in side effects such as antibiotic-
prebiotics to impact immune responses and to reduce associated diarrhoea (AAD). The estimated incidence
the risk of infections has been the subject of a number of of AAD is as high as 25% for some antibiotics and this
human studies (discussed below). Such results, combined can lead to patients failing to complete the course of
treatment. There is evidence that specific probiotics can The microbiota in pre-term infants is restricted and
reduce the risk of AAD and, indeed, several meta-analyses differs in composition from those in healthy, full-term
conclude that there may be as much as a halving of the infants. In particular, potentially beneficial bifidobacteria
risk of AAD in adults or the elderly, although the effect is are not well established in the pre-term neonatal gut.
less consistent in children. The observed effects relate to The microbiota is further challenged by environmental
a limited number of specific probiotic strains. In the case bacteria from the hospital milieu and the common use
of prebiotics, it has been shown that FOS administration of antibiotics in pre-term infants, putting this population
following an antibiotic treatment reduced the re- at increased risk of necrotising enterocolitis (NEC).
occurrence of AAD from more than 30% in the control Although the use of probiotics is not yet established in
group to less than 10% in the prebiotic group. As this was clinical practice, several trials have shown that specific
not associated with a decrease in subjects testing positive probiotic strains can reduce the risk of NEC. Additional
for C. difficile, this could suggest that the prebiotic had a studies are needed to clarify the preferred strain and dose
stabilising effect on the microbiota, supporting a return of recommendations. Furthermore, the use of live microbes
eubiosis. in such a susceptible population makes confirmation of
safety for this use a prime objective.
Clostridium difficile infection is a frequent cause of
diarrhoea in institutionalised populations, for example Other infections
in hospitals and in long-term care homes. It is often
associated with antibiotic use but it can occur as a result There has been a number of studies on various age groups
of other risk factors such as age greater than 65 years to investigate the potential for probiotics to impact the
or a compromised immune system owing to illness, susceptibility to upper respiratory tract infection (URTI)
medication or GI surgery. So far, the results of research and its duration and symptoms. Studies were conducted
to investigate whether probiotics can reduce the risk of with a range of different strains; some strains reduced
C. difficile infection or reduce the severity or duration of incidence, some reduced duration and most had effects
symptoms in adults are promising but further confirmatory on symptoms. The evidence is promising, but the range
studies are needed. of strains and the variation in age groups and study
design prevent any firm conclusions. Evidence for an
A bacterium known as Helicobacter pylori is present in effect of prebiotics is limited to a recent, large, long-term
the stomach of a small proportion of young adults but study in which infants consuming formula supplemented
in as many as 50% of those aged 60 years and over. It with a specific GOS/long-chain FOS combination were
colonises the mucous layer next to the gastric epithelium less prone to upper URTI and associated fever than were
and in some people can cause acute gastritis (i.e. pain, those infants fed formula without a prebiotic.
bloating, nausea and vomiting) and can lead to chronic
gastritis and peptic ulcers. Treatment involves long- There has also been interest in the use of probiotics in
term administration of strong antibiotics and although urogenital medicine. Certain probiotic strains have been
probiotics do not speed the eradication of H. pylori, some shown to improve recovery from bacterial vaginosis
have been shown in several studies to reduce the side during antibiotic treatment. Potential mechanisms for the
effects of treatment and may result in less disturbance of effect include anti-microbial antagonism, restoration of
the microbiota. balanced microbiota or an enhanced immune response.
Vaccinations As noted, the prevalence of allergy has increased in

westernised societies. There is growing evidence that
Animal studies have convincingly demonstrated
the nature of microbiota acquired by the infant in the
that certain probiotic strains can both enhance the
postnatal period has an important bearing on maturation
immune response to a vaccine and reduce the risk of
of the immune system. There is some indication that
subsequent infection. Human studies are much fewer,
atopic children tend to have a degree of dysbiosis, with
but an increasing number of well-controlled trials are
more clostridia and fewer bifidobacteria than non-atopic
being conducted. Preliminary evidence indicates that
individuals. In addition, data suggests that breast-fed
the response to vaccines against influenza, cholera
infants are less prone to allergic conditions. It has thus
or childhood diseases can be enhanced by selected
been suggested that prebiotics may help reduce the risk
probiotics, as measured by the number of subjects who
of developing atopy or reduce the associated symptoms
respond to the vaccine or an increase in the level of serum
of atopic eczema or allergic rhinitis. There is promising
immunoglobulins. The effects are strain-specific in terms
evidence, based on a follow-up of one intervention,
of efficacy of the probiotics and, in the case of influenza,
that not only can prebiotic-supplemented infant formula
specific to the pathogen strains. In one study, there was
reduce susceptibility to atopy but that the benefits persist
limited evidence that subsequent risk of infection with
up to 2 years of age. Furthermore, studies in infants at high
the influenza virus was reduced. In the case of prebiotics,
risk of allergy who were fed supplemented formulas for 6
although evidence in animals seemed promising, clinical
months had reduced levels of IgE and some IgG types.
studies have not yet been supportive of an effect.
There have been several studies on the impact of
Allergic conditions probiotics on the development of allergic symptoms in
Allergy can be defined in simple terms as an inappropriate infants at high risk of developing atopic disease. In most
immune reaction or over-reaction to an otherwise of these studies, the mother consumed the probiotic prior
harmless foreign antigen (mostly proteins or peptides). to birth and the infant was administered the probiotic
In medical terms, it is described as a hypersensitivity after birth. Results showed a decreased risk of eczema at
reaction mediated by specific antibodies (IgE) or cell- 2 years of age and beyond. Overall, results of the studies
based mechanisms. Common allergies include reactions point towards strain-specificity and also hint towards
to certain food proteins (e.g. milk, eggs, peanuts, tree two separate windows of opportunity: first, the maternal
nuts, soy, wheat gluten, fish, shellfish and shrimp) or to consumption of probiotics during the perinatal period
environmental allergens such as pollen (hay fever), house and, second, the use of probiotics during weaning. Past
dust mites and pet hair. Food allergies are more common and ongoing studies have also targeted the management
in infants and children than in adults. The most serious or reduction of allergic symptoms such as those linked to
form of allergy resulting in anaphylaxis (which can be fatal atopic eczema or allergic rhinitis; results are promising
when the throat and respiratory tract swell and restrict but not yet conclusive. This probably reflects the
breathing) is rare, albeit a lifelong concern. Less severe complexity of the allergic diseases spectrum and the fact
symptoms of allergies are more common (prevalence is that a range of different clinical designs was used.
about 2% for food allergies and up to 30% for respiratory
allergies) and can substantially reduce the quality of life
for allergic subjects.
PROBIOTICS AND GI tract and its microbiota

PREBIOTICS: As noted, bifidobacteria and lactobacilli in the colon
preferentially ferment carbohydrates that escape
MECHANISMS OF ACTION digestion in the upper GI tract, resulting in a reduced pH
of the colon. Bifidobacteria can ferment fructans because
they have an enzyme, β-fructofuranosidase, that other
bacteria either lack or have present at a lower activity,
Overall mechanism thus giving them a competitive advantage when exposed
Both probiotics and prebiotics are thought to work largely to fructans in the human gut. Similarly, the presence
through direct or indirect effects on the gut microbiota of β-galactosidase in lactobacilli or streptococci exerts
and environment and/or on host function. In the case a competitive advantage in GOS fermentation. The
of probiotics, a live micro-organism is consumed, in a metabolism of prebiotic fructans by bifidobacteria yields
range of dosages, spanning from ~108 to 1012 cells/day, mainly the acidic compounds acetate and lactate. Cross-
depending on the product. This large number of microbes feeding of these fermentation products to other species
has the potential for a greater impact in the upper GI tract gives rise to butyrate and propionate. Butyrate and
where lower densities of micro-organisms are found, but propionate are also formed from the direct fermentation
is also thought to impact the colon. Prebiotics enhance of other dietary carbohydrates.
the growth of the endogenous microbiota or possibly The benefits of a lower pH in the colon are that it
stimulate the growth of probiotics when provided encourages the multiplication and survival of commensal
concurrently. Thus, probiotics and prebiotics share many organisms that prefer acidic conditions and generally
common mechanisms of action mediated through an inhibits the ability of some pathogens to adhere, grow,
impact of microbes on the host and these are discussed translocate across the epithelium or colonise the GI tract.
below. In the case of health effects that relate only to Furthermore, butyrate has long been known, from in
prebiotics or only to probiotics, the mechanisms are less vitro studies on fermentable dietary fibres, to enhance
well known and have been alluded to in the section on mucosal cell differentiation and this may also promote
health effects. the barrier function of the epithelium.
Probiotics and prebiotics (via their stimulation of Saccharolytic fermentation concomitantly reduces the
commensal organisms) act on and interact with the host potentially adverse effects of protein fermentation and
by two main modes of action, or a combination of actions other processes, which give rise to nitrogen and sulphur-
(Figure 6 – see page 24): containing compounds such as ammonia, N-nitroso- and
• Impact of micro-organisms or their metabolites/ azo- compounds as well as sulphides.
enzymes on the host’s GI tract and its microbiota Many bacteria produce bacteriocins, which are peptides
• Interaction with the host’s cells and immune system or proteins that are intended to reduce the survival of
competing organisms. Bacteriocins produced by probiotic
bacteria have been observed in in vitro studies to decrease
the ability of pathogens such as E. coli O157:H7 to
adhere to and invade cultured intestinal cells. Bacteriocin
FIGURE 6.
Diagram illustrating potential or known mechanisms of probiotics action
These mechanisms include (1) competition for dietary ingredients as growth substrates, (2) bioconversion of, for example, sugars
into fermentation products with inhibitory properties, (3) production of growth substrates, for example, EPS or vitamins, for other
bacteria, (4) direct antagonism by bacteriocins, (5) competitive exclusion for binding sites, (6) improved barrier function, (7) reduction
of inflammation, thus altering intestinal properties for colonisation and persistence within, and (8) stimulation of innate immune
response (by unknown mechanisms). IEC, epithelial cells; DC, dendritic cells; T, T cells. Source: O’Toole and Cooney (2008)
production following prebiotic administration has also bacteriocins. In this case, such organisms lose their ability
been reported. This may be one of the mechanisms by to prevent adherence and translocation of pathogens
which probiotics and prebiotics decrease the infection during in vitro studies and/or to reduce infection rates/
rate in humans and animals and increase the survival of survival in infected animals. In addition, probiotics have
mice in studies where a lethal challenge with a pathogen been shown in vitro to alter the gene expression of certain
is performed. Additional supporting evidence for this pathogens thereby reducing their virulence.
mechanism comes from studies using probiotic bacteria
Some probiotics may improve the barrier function of the
modified in such a way that they can no longer produce
mucus layer or epithelial cells. Evidence from cell culture
studies suggests that an increase in the production Cross-talk with the host
of mucins may result from an enhancement of gene
expression in the mucus-producing Goblet cells that line The most complex of the postulated mechanisms by which
the GI tract. Increasing the mucous layer helps protect probiotics and stimulated endogenous microbes may act
the epithelial cells from potential pathogen translocation is the interaction with the GI immune cells and lymphoid
and may enhance the clearance of pathogens from the tissue to modulate the immune and inflammatory
GI tract. responses of the host, which might lead to the potential
for an impact beyond the gut (Figure 7 – see page 26).
Probiotics may also enhance the ability of specialised
Paneth cells in the small intestine to produce the The mammalian immune system is generally considered
antibacterial peptides known as defensins. This to consist of two major arms: the innate (or non-specific
hypothesis is supported by in vitro studies, using intestinal immediate) immune response and the acquired (or
epithelial (e.g. Caco-2) cells grown in tissue culture, that specific adaptive) immune response. Both parts of the
have shown that certain probiotics can stimulate human immune system are extremely complex and involve
β-defensin mRNA expression and peptide secretion. cells (cellular immunity) and other components secreted
into the blood (e.g. antibodies and cytokines). The two
In vitro studies suggest that probiotics and prebiotics arms work together to protect the host from pathogens
may affect the barrier function of the epithelium itself by (bacteria, viruses, fungi), other foreign materials (antigens)
enhancing the resistance of tight junctions, possibly via and also from tumour cells arising in the host. For more
an effect on tight junction proteins (e.g. occludins and information, see the ILSI Europe Concise Monograph on
claudins). Increased expression of genes encoding tight Nutrition and Immunity in Man (ILSI, 2011).
junction proteins has recently been shown in a study
conducted in human volunteers administered a specific Through so-called bacterial–epithelial cell “cross-talk”,
Lactobacillus strain. it seems that ingested and endogenous microbes can
impact both the innate and the adaptive responses of the
Animal and in vitro studies have found that specific host immune system. The interaction between microbial
probiotics can compete with pathogens for receptor cells (commensal, probiotic or pathogen) and host cells
sites on epithelial cells or in the mucous layer, thereby is mediated by the interaction with specific receptors
preventing pathogens from adhering or translocating. such as Toll-like receptors (TLR) that are associated with
In contrast, other probiotics may directly bind to the cells lining the mammalian GI tract. The activation of
pathogen, thus reducing its ability to colonise the these receptors initiates a cascade of concerted immune
intestine. There is good evidence from studies on mice signals leading to different responses. For example,
that feeding on certain probiotic strains can greatly the response can ensure a balanced maturation of
reduce the ability of pathogens such as S. typhimurium T cells (Th1 versus Th2) and T-regulatory cells, which
and pathogenic E. coli to translocate and invade the liver allows an appropriate response to potential pathogens
and spleen. In vitro studies showed that the same strains and food antigens. An inappropriate T cell response is
compete with the ability of pathogens to adhere to cells. thought to be one of the features of allergic conditions,
Influence on pathogen translocation in infected animal as mentioned previously. Further, activation of the
models has also been shown for some prebiotics. immune pathways can also result in B cell differentiation
and production of protective antibodies, such as IgA,
FIGURE 7.
The three levels of action of a probiotic
Probiotic bacteria can interfere with the growth or survival of pathogenic micro-organisms in the gut lumen (level 1). Probiotic bacteria can
improve the mucosal barrier function and mucosal immune system (level 2) and, beyond the gut, have an effect on the systemic immune system,
as well as other cell and organ systems such as liver and brain (level 3). Source: Rijkers (2010)
secreted into the intestinal lumen. Along the same lines, The activity of phagocytic cells (neutrophils and
the ingestion of specific probiotic strains or prebiotics in macrophages) and natural killer (NK) cells (non-T non-B
human and animal studies has been found to stimulate lymphocytes), which are part of the innate immune
an increase in the anti-inflammatory cytokines, such as response, is also modulated in animals and humans by
IL-10 and TGF-β, and a decrease in the expression of various probiotics and to some extent by prebiotics or
pro-inflammatory cytokines, such as TNF-α and IFN-γ. It synbiotics. In addition, animal studies have suggested
is proposed that these changes in cytokine balance could that the so-called G-protein receptors in certain white
be a mechanism by which prebiotics and probiotics may blood cells may act as receptors for SCFA, increased
be able to mitigate chronic intestinal inflammation. levels of which result from the ingestion of prebiotics,
thus opening up the possibility of alternative mechanisms

impacting the immune system.
OVERALL CONCLUSIONS
Although studies in humans have found changes in
biomarkers such as cytokine levels and changes in the
number and activity of immune cells, it is nevertheless of The science around the concept of probiotics and
prime importance to have studies in human subjects that prebiotics continues to expand. Current global research
also measure clinical outcomes. Clinical measures, such efforts have greatly contributed to the understanding of
as a reduced incidence of infection or enhanced immune the role of GI commensal organisms in their extraordinary
response to a vaccine, can then be linked to measures symbiotic relationship with humans. Continued research
of humoral or cellular immune biomarkers. Even into the microbiota will no doubt help lead to an improved
though results from animal studies cannot necessarily insight into the impact of probiotics and prebiotics on
be extrapolated to humans, in vivo studies in animal human health.
models represent a valuable means of understanding Probiotics are designed to provide added functions that
the complex signalling cascade underlying a protective can compensate for, substitute for, or add to the gut
immune response. microbiota, and therefore impact the host directly or
indirectly through “cross-talk” with the gut microbiota
and/or the host. In addition, the effects may be local in the
GI tract or systemic. Prebiotics are designed to improve
the intrinsic microbiota by selectively stimulating those
groups that are thought important for eubiosis.
Research over past decades has demonstrated potential
health benefits of dietary probiotics and prebiotics and
contributed to our understanding of the mechanisms
by which these effects are brought about. The most
commonly reported impact of probiotics and prebiotics
is on intestinal function, including transit time, AAD and
infectious diarrhoea. Evidence continues to emerge
that probiotics and prebiotics have an influence on the
immune system and thereby may enhance resistance to
infections, particularly those of the GI or respiratory tract,
and help to mitigate allergies, particularly in infants and
young children. Evidence is gradually developing for the
potential for probiotics and prebiotics to impact other
conditions of the GI tract, such as IBD, IBS and colon
cancer. In the case of prebiotics, a well-established role
in enhancing calcium absorption remains to be a proven
benefit for bone health.
An emerging role for prebiotics and probiotics in

appetite control and weight management could be
very important. An expanding area of interest for both
prebiotics and probiotics is the investigation of their
potential for an anti-inflammatory role in conditions
beyond the gut such as cardiovascular disease, obesity
and metabolic syndrome.
One critically important fact to bear in mind is that
reported benefits of probiotics should be considered
strain-specific unless otherwise demonstrated. Prebiotics
are also likely to have substance-specific effects. Thus, for
both probiotics and prebiotics it is vital that future human
studies take this into account. Such studies, apart from
establishing the effects of each ingredient, should also
aim to improve our understanding of the mechanisms
of action and, if possible, lead to validated biological
markers.
It must be remembered when considering studies
on prebiotics that only a few prebiotics are currently
established. Similarly, only a limited number of microbes
have been documented as probiotic. In all cases, it is
clear that prebiotics and probiotics must be consumed
regularly in order to confer a benefit.
This monograph attempts to summarise the science
and principles valid for prebiotics and probiotics today.
It is noteworthy that these ingredients can be readily
incorporated into a balanced diet and that there is a
growing body of evidence for their potential health
benefits.
ABBREVIATIONS
AAD Antibiotic-associated diarrhoea

CD Crohn’s disease
CFU Colony-forming units
DP Degree of polymerisation, i.e. the number of monomers in a molecule
FOS Fructo-oligosaccharides – typically applied to mixtures of DP3–DP9
GALT Gut-associated lymphoid tissue
GI Gastro-intestinal
GOS Galacto-oligosaccharides – typically applied to mixtures of DP3–DP9
IBS Irritable bowel syndrome
IBD Inflammatory bowel disease
IL Interleukin
NEC Necrotising enterocolitis
QPS Qualified presumption of safety
SCFA Short chain fatty acids
TLR Toll-like receptors
UC Ulcerative colitis
URTI Upper respiratory tract infection
GLOSSARY Eubiosis: Formally referred to as “normobiosis”, this

characterises the composition of a stable or balanced
gut microbiota in a healthy individual. There is
incomplete understanding of what constitutes
Antibody: A specific protein produced in the blood or eubiosis and, hence, no general definition in terms of
tissues as part of the immune response to a foreign bacterial composition or function.
antigen such as a bacterium, toxin or food protein. Fermentation: The anaerobic oxidation of organic
The antibody interacts with the antigen, thereby compounds to generate metabolic energy in the
inactivating it and thus forming the basis of immunity. absence of oxygen as an electron sink. Reduction
Antigen: A substance that the body recognises as foreign equivalents are released as hydrogen, ammonia,
and that can evoke an immune response. Most often, hydrogen sulphide, methane, organic acids or
an antigen is a peptide or protein (e.g. bacterial alcohols. For example, the oxidation of carbohydrates
antigen, food antigen or toxin). to short chain fatty acids (SCFA), ethanol, lactic acid
and/or gases to produce energy in the form of ATP.
Atopy: A genetic susceptibility to exhibit hypersensitivity
reactions (eexaggerated immune responses) to Microbe/micro-organism: Small, often single-cell
common antigens e.g. atopic eczema in response to a organisms including bacteria, archaea, yeast,
common foodstuff. mould, fungi, algae and plankton (fungi may also
be multicellular). Although definitions vary, we have
Commensal: From the Latin for “common table”. It taken the view that microbes do not include viruses.
means two organisms living together in a way that is
either beneficial to both and or that, at least, is not Microbiota: All the microbes that are found in a particular
harmful to either. Hence, commensal bacteria live in region or habitat; hence, gut microbiota describes
the human gut and may be neutral or beneficial. the whole microbial population found in the gut or
gastrointestinal tract. The term “microflora” is no
Cytokines: Low molecular weight proteins (other than longer used.
antibodies) produced by various cell types and
involved in cell-to-cell communication and control of Oligosaccharide: A carbohydrate that consists of 3–9
the inflammatory and immune response. Cytokines monosaccharide units joined by glycosidic linkages.
include interferons, interleukins and lymphokines. Some are prebiotics.
Dysbiosis: The condition of the microbiota of the gut in Polysaccharide: A carbohydrate comprising ten or more
which one or a few potentially harmful micro-organisms monosaccharide units. Some are prebiotics.
are present in high numbers, thus creating a disease- Taxonomy: The science of identifying species and
prone situation or resulting in otherwise noticeable arranging them into a classification.
disturbances of the microbiota such as liquid stools,
gastrointestinal infections or inflammations.
SOURCE MATERIALS AND ILSI Europe (2010). Guidance for assessing the probiotics
beneficial effects: how to fill the GAP. Journal of Nutrition,
FURTHER READING 140 (Suppl 3S-I): 671S-721S. Series of papers presented
at a workshop “Guidance for assessing the probiotics
beneficial effects: how to fill the GAP” organised by the
ILSI Europe Probitoics Task Force in association with the
Blaut, M. and Clavel, T. (2007). Metabolic diversity of the International Dairy Federation, Montreux, Switzerland,
intestinal microbiota: implications for health and disease. 22–24 May 2008.
Journal of Nutrition, 137(3 Suppl 2):751S-755S.
FAO/WHO (2002) Joint FAO/WHO Working Group
Braegger C., et al. (2011). Supplementation of infant report on drafting guidelines for the evaluation of
formula with probiotics and/or prebiotics: a systematic probiotics in food. London, Ontario, Canada, April 30
review and comment by the ESPGHAN committee on and May 1, 2002.
nutrition. Journal of Pediatric Gastroenterology and http://www.who.int/foodsafety/fs_management/en/
Nutrition, 52:238-250. probiotic_guidelines.pdf
Cani P.D. and Delzenne N.M. (2011). The gut microbiome FAO/WHO (2001) Joint FAO/WHO Expert Consultation
as therapeutic target. Pharmacology & Therapeutics, on evaluation of health and nutritional properties of
130:202-212. probiotics in food including powder milk with live lactic
acid bacteria. Cordoba, Argentina, October 2001.
EFSA (2011). EFSA Panel on Dietetic Products, Nutrition
http://www.who.int/foodsafety/publications/fs_
and Allergies (NDA); guidance on the scientific
management/en/probiotics.pdf
requirements for health claims related to gut and immune
function. EFSA Journal, 9:1984. MetaHIT (2008) Metagenomics of the human intestinal
tract.
EFSA (2011). EFSA Panel on Dietetic Products, Nutrition
http://www.metahit.eu/
and Allergies (NDA); general guidance for stakeholders
on the evaluation of Article 13.1, 13.5 and 14 health O’Toole, P.W. and Cooney, J.C. (2008). Probiotic bacteria
claims. EFSA Journal, 9:2135. influence the composition and function of the intestinal
microbiota. Interdisciplinary Perspectives on Infectious
Gibson, G.R., et al. (2011). Dietary prebiotics: current
Diseases, 2008:175285.
status and new definition. IFIS Functional Foods Bulletin,
7:1–19. Rijkers, G.T. et al. (2010) Guidance for substantiating
the evidence for beneficial effects of probiotics: current
HMP (2012) Human Microbiome Project. National
status and recommendations for future research. Journal
Institutes of Health, Bethesda, MD, USA.
of Nutrition, 140:6715-6765
www.hmpdacc.org
Roberfroid, M., et al. (2010). Prebiotic effects: metabolic
ILSI Europe (2011) ILSI Europe Concise Monograph on
and health benefits. Commissioned by the ILSI Europe
Nutrition and Immunity in Man, 2nd Edition. ILSI Europe,
Prebiotics Task Force. British Journal of Nutrition,
Brussels.
104(Suppl. S2):S1-63
http://www.ilsi.org/Europe/Publications/Nutrition%20
and%20Immunity.pdf
Salminen et al., (1998) Functional food science and

gastrointestinal physiology and function. British Journal
of Nutrition 80(Suppl. 1):S147–S171.
Sanders, M.E., et al. (2007). Probiotics: their potential to
impact human health. Council for Agricultural Science
and Technology (CAST), Issue Paper 36. CAST, Ames,
Iowa.
Sanders, M.E. (2009). How do we know when something
called “probiotic” is really a probiotic? A guideline for
consumers and health care professionals. Functional
Food Reviews, 1:3–12.
Sanders, M.E. (2011). Impact of probiotics on colonizing
microbiota of the gut. Journal of Clinical Gastroenterology,
45(Suppl. 3): S115-S119.
Spahn, T.W. and Kucharzik, T. (2004) Modulating the
intestinal immune system: the role of lymphotoxin and
GALT organs. Gut, 53:456-465.
World Gastroenterology Organisation (2011) Practice
guideline: probiotics and prebiotics, October 2011.
http://www.worldgastroenterology.org/probiotics-
prebiotics
ILSI Europe Concise Monographs
• Alcohol – Health Issues Related to Alcohol Consumption ILSI Europe Concise Monographs can be downloaded
• A Simple Guide to Understanding and Applying the Hazard from:
Analysis Critical Control Point Concept www.ilsi.org/Europe/Pages/ConciseMonographSeries.
• Calcium in Nutrition aspx
• Carbohydrates: Nutritional and Health Aspects ILSI Europe publishes also Reports in its Report Series.
• Caries Preventive Strategies ILSI Europe Reports can be downloaded from:
• Concepts of Functional Foods www.ilsi.org/Europe/Pages/ReportSeries.aspx
• Dietary Fibre
ILSI Europe publishes articles and proceedings in
• Food Allergy
peer-reviewed journals as well. Some of them can be
• Food Biotechnology – An Introduction downloaded from:
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Health and Safety
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od International Life Sciences Institute

ILSI EUROPE CONCISE MONOGRAPH SERIES

For more information about ILSI Europe, please contact

ILSI Europe a.i.s.b.l.

Author: Nino Binns, NB Consulting (UK)

INTRODUCTION consuming large amounts of fermented milk products

ingredient that results in specific changes in the

Bacteria Mode of action on substrates Fermentation products

Source: Prof. R. Rastall, University of Reading, UK

of current research on probiotics and prebiotics also

Modern molecular methods should be used for species Safety

or if any safety concerns can be defined and excluded,

Criteria for prebiotic selection

HEALTH EFFECTS response to a vaccine or reduction in the duration of

Vaccinations As noted, the prevalence of allergy has increased in

PROBIOTICS AND GI tract and its microbiota

thus opening up the possibility of alternative mechanisms

An emerging role for prebiotics and probiotics in

AAD Antibiotic-associated diarrhoea

GLOSSARY Eubiosis: Formally referred to as “normobiosis”, this

Salminen et al., (1998) Functional food science and

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