Functional Cultures and Health Benefits PDF

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International Dairy Journal 17 (2007) 12621277

www.elsevier.com/locate/idairyj
Review
Functional cultures and health benets

Nagendra P. Shah
School of Molecular Sciences, Victoria University, P.O. Box 14428, Melbourne, Vic. 8001, Australia
Received 25 September 2006; accepted 22 January 2007
Abstract
A number of health benets have been claimed for probiotic bacteria such as Lactobacillus acidophilus, Bifidobacterium spp., and
L. casei. These benets include antimutagenic effects, anticarcinogenic properties, improvement in lactose metabolism, reduction in
serum cholesterol, and immune system stimulation. Because of the potential health benets, these organisms are increasingly being
incorporated into dairy foods, particularly yoghurt. In addition to yoghurt, fermented functional foods with health benets based on
bioactive peptides released by probiotic organisms, including Evoluss and Calpiss, have been introduced in the market. To maximize
effectiveness of bidus products, prebiotics are used in probiotic foods. Synbiotics are products that contain both prebiotics and
probiotics.
r 2007 Elsevier Ltd. All rights reserved.
Keywords: L. acidophilus; Bifidobacterium; L. casei; Health benets; Stability; Bioactive peptides
Contents
1.
2.
3.
4.
5.
6.
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Probiotic bacteria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Health benets of functional probiotic cultures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.1. Antimicrobial activity and gastrointestinal infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.2. Effectiveness against diarrhoea . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.3. Improvement in lactose metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.4. Antimutagenic properties. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.5. Anticarcinogenic properties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.6. Reduction in serum cholesterol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.7. Helicobacter pylori infection. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.8. Inammatory bowel disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.9. Immune system stimulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Prebiotics and synbiotics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Alternate products for incorporating probiotics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5.1. Products based on bioactive peptides released from milk proteins by proteolytic probiotics . . . . . . . . . . . . . . . . . .
Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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1. Introduction
Tel.: +61 3 9919 8289; fax: +61 3 9919 8284.
E-mail address: Nagendra.Shah@vu.edu.au.

0958-6946/$ - see front matter r 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.idairyj.2007.01.014
At the beginning of this century, Nobel Laureate Elie

Metchnikoff, at the Pasteur Institute, linked health and
ARTICLE IN PRESS
N.P. Shah / International Dairy Journal 17 (2007) 12621277
longevity to ingestion of bacteria present in yoghurt

(monograph reprinted in: Metchnikoff, 2004). It was
believed that bacteria present in yoghurt controlled
infections caused by enteric pathogens and regulate
toxaemia, both of which play a major role in ageing and
mortality. This observation provided a major boost to the
manufacture and consumption of yoghurt. The health
benets derived by the consumption of foods containing
Lactobacillus acidophilus, Bifidobacterium and L. casei are
now well documented.
Functional foods are dened as foods that contain some
health-promoting component(s) beyond traditional nutrients (Shah, 2001). Functional foods are also known as
designer foods, medicinal foods, nutraceuticals, therapeutic
foods, superfoods, foodiceuticals, and medifoods (Shah,
2001). In general, the term refers to a food that has been
modied in some way to become functional. One way in
which foods can be modied to become functional is by
addition of probiotics: the word probiotic originated from
Greek meaning for life. Probiotic foods are dened as
food containing live microorganisms believed to actively
enhance health by improving the balance of microora in
the gut (Fuller, 1992). Probiotic yoghurts, for instance,
contain probiotic bacteria as health promoting components
beyond traditional nutrients.
Traditionally, yoghurt is manufactured using Streptococcus thermophilus and L. delbrueckii ssp. bulgaricus as
starter cultures. These organisms are claimed to offer some
health benets as postulated by Metchnikoff; however,
they are not natural inhabitants of the intestine. Therefore,
for yoghurt to be considered as a probiotic product,
L. acidophilus, Bifidobacterium and L. casei are incorporated as dietary adjuncts. Products such as Yakult contain
the L. acidophilus Shirota strain. Whilst fermented milk
products containing only one or more of these three
adjuncts could be manufactured, the longer incubation
period required and poorer resultant product quality are
the two main factors that preclude such practice commercially. Thus, the normal practice is to make product
with both starter organisms, e.g., Str. thermophilus and
L. delbrueckii ssp. bulgaricus, and one or more species of
probiotic bacteria.
New fermented products containing L. acidophilus,
Bifidobacterium spp., L. casei Shirota, L. rhamnosus GG,
and L. reuteri have been developed in Europe. However,
L. acidophilus and Bifidobacterium spp. are most commonly
used as probiotics. It is estimated that over 70 products
containing L. acidophilus and Bifidobacterium spp., including yogurt, buttermilk, frozen desserts and milk powder,
are produced worldwide. Probiotic organisms themselves
are also available as powders, capsules and tablets.
2. Probiotic bacteria
Probiotics have been consumed in foods such as yoghurt
for perhaps thousands of years, and while the cultures
were thought to have benecial effects, it was not until the
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1900s that scientists began to investigate the reasons for

those benets. A number of genera of bacteria (and yeast)
are used as probiotics, including Lactobacillus, Leuconostoc, Pediococcus, Bifidobacterium, and Enterococcus, but
the main species believed to have probiotic characteristics
are L. acidophilus, Bifidobacterium spp., and L. casei.
Members of the genera Lactobacillus and Bifidobacterium
have a long and safe history in the manufacture of dairy
products and are also found as a part of gastrointestinal
microora. Probiotic bacteria with desirable properties and
well-documented clinical effects include L. johnsonii La1,
L. rhamnosus GG (ATCC 53103), L. casei Shirota,
L. acidophilus NCFB 1478, B. animalis Bb12 and L. reuteri
(Shah, 2004).
At present, 56 species of the genus Lactobacillus have
been recognized (Table 1). L. acidophilus is the most
commonly suggested organism for dietary use. Growth of
L. acidophilus occurs at as high as 45 1C, however, the
optimum growth temperature is between 3540 1C. The
organisms grow in slightly acidic media at pH of 6.44.5,
but growth ceases when a pH of 4.03.6 is reached. The
acid tolerance of the organisms varies from 0.3% to 1.9%
titratable acidity, with an optimum pH at 5.56.0 (Curry &
Crow, 2003; Shah, 2003).
L. acidophilus tends to grow slowly in milk, leading to
the risk of overgrowth of undesirable microorganisms.
Ironically, most strains of L. acidophilus do not survive well
in fermented milk due to the low pH, and it is difcult to
maintain large numbers in the product. The poor growth is
partly related to low concentration of small peptides and
free amino acids in milk, which would be insufcient to
support the bacterial growth.
Table 1
Lactobacilli used as probiotic culturesa
Species
Strains
L.
L.
L.
L.
L.
L.
L.
L.
L.
L.
L.
L.
L.
L.
L.
L.
L.
L.
L.
L.
LA-1/LA-5 (Chr. Hansen)

NCFM (Rhodia)
La1 (Nestle)
DDS-1 (Nebraska Cultures)
SBT-2062 (Snow Brand Milk Products)
Lb12
L1A (Essum AB)
(Danone)
299v, Lp01
GG (Valio)
GR-1 (Urex Biotech)
LB21 (Essum AB)
SD2112/MM2 (Biogaia)
271 (Probi AB)
(Probi AB)
SD2112 (also known as MM2)
Shirota (Yakult)
CRL 431 (Chr. Hnasen)
RC-14 (Urex Biotech)
B02
acidophilus
acidophilus
acidophilus Johsonii
acidophilus
acidophilus
bulgaricus
lactis
casei Immunitas
plantarum
rhamnosus
rhamnosus
rhamnosus
reuteri
rhamnosus
plantarum
reuteri
casei
paracasei
fermentum
helveticus
a
Adapted from Krishnakumar and Gordon (2001), Holm (2003), Playne
et al. (2003); Shah (2004).
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Bifidobacterium are normal inhabitants of the human

gastrointestinal tract. Recent in vivo scientic studies using
animals or human volunteers have shown that consumption of live Bifidobacterium has an effect on the gut
microora. Selected strains survive stomach and intestinal
transit and reach the colon in abundant numbers. Newborns are colonized with Bifidobacterium within days
after birth and the population appears to be relatively
stable until advanced age, when a decline in their numbers
occurs. However, diet, antibiotics, and stress are reported
to inuence the population of Bifidobacterium in the
intestines.
Presently, there are 29 species in the genus Bifidobacterium (Table 2), 14 of which are isolated from human sources
(i.e., dental caries, faeces and vagina), 12 from animal
intestinal tracts or rumen, and 3 from honeybees.
Bifidobacterium species found in humans are: B. adolescentis, B. angulatum, B. bifidum, B. breve, B. catenulatum,
B. dentium, B. infantis, B. longum, and B. pseudocatenulatum. B. breve, B. infantis, and B. longum are found in
human infants; B. adolescentis, and B. longum are found in
human adults (Shah & Lankaputhra, 2002).
The optimum pH for the growth of Bifidobacterium is
6.07.0, with virtually no growth at pH 4.55.0 and below
or at pH 8.08.5 and above. Optimum growth occurs at a
temperature of 3741 1C, the minimum and maximum
growth temperatures are 2528 and 4345 1C, respectively.
The main probiotic organisms that are currently used
worldwide belong to the genera Lactobacillus and Bifidobacterium. A limited number of investigations have also
been carried out into the potential properties of genera
including Pediococcus, Leuconostocs, and Propionibacterium and also of Enterococcus faecium. Ent. faecium is
Table 2
Bifidobacterium cultures used as probiotic culturesa
Species
Strains
B. adolescentis
B. longum
B. longum
ATCC 15703, 94-BIM

BB536 (Morinaga Milk Industry)
SBT-2928 (Snow Brand Milk
Products)
Yakult
Bb-11
Bb-12 (Chr. Hansen)
B. breve
B. bifidus
B. lactis (reclassied as B.
animalis)
B. essensis
B. lactis
B. infantis
B. infantis
B. infantis
B. infantis
B. laterosporus
B. lactis
B. longum
B. lactis DR10/HOWARU
Danone (Bioactivia)
Bb-02
Shirota
Immunitass
744
01
CRL 431
LaftiTM, B94 (DSM)
UCC 35624 (UCCork)
Danisco
a
Adapted from Krishnakumar and Gordon (2001); Holm (2003); Playne
et al. (2003); Shah (2004).
more pH stable than L. acidophilus and produces

bacteriocins against some enteropathogens. These properties make this organism attractive as a probiotic. From
published reviews, four strains with the most published
clinical data are L. rhamnosus GG, L. casei Shirota,
B. animalis Bb-12, and Saccharomyces cerevisiae Boulardii
(Shah, 2006b).
3. Health benets of functional probiotic cultures
A number of health benets are claimed in favour
of products containing probiotic organisms including
antimicrobial activity and gastrointestinal infections, improvement in lactose metabolism, antimutagenic properties, anticarcinogenic properties, reduction in serum
cholesterol, anti-diarrhoeal properties, immune system
stimulation, improvement in inammatory bowel disease
and suppression of Helicobacter pylori infection (Kurmann
& Rasic, 1991; Shah, 2000b, 2004). Some of the health
benets are well established, while other benets have
shown promising results in animal models. However,
additional studies are required in humans to substantiate these claims. Health benets imparted by probiotic
bacteria are strain specic, and not species- or genusspecic. It is important to note that no strain will provide all proposed benets, not even strains of the same
species, and not all strains of the same species will be
effective against dened health conditions. The strains
L. rhamnosus GG (Valio), S. cerevisiae Boulardii (Biocodex), L. casei Shirota (Yakult), and B. animalis Bb12
(Chr. Hansen) have the strongest human health efcacy
data with respect to management of lactose malabsorption, rotaviral diarrhoea, antibiotic-associated diarrhoea,
and Clostridium difficile diarrhoea (Playne, Bennet, &
Smithers, 2003; Shah, 2006a, b). There is sufcient evidence to support the view that oral administration of
Lactobacillus and Bifidobacterium is able to restore the
normal balance of microbial populations in the intestine
(Shah, 2006b).
3.1. Antimicrobial activity and gastrointestinal infections
Probiotic bacteria produce organic acids, hydrogen
peroxide and bacteriocins as antimicrobial substances that
suppress the multiplication of pathogenic and putrefying
bacteria. Lactic and acetic acids account for over 90% of
the organic acids produced. Lowering of pH due to lactic
acid or acetic acid produced by these bacteria in the gut has
a bacteriocidal or bacteriostatic effect. Both Bifidobacterium and L. acidophilus show antagonistic effects towards
enteropathogenic Escherichia coli, Salmonella typhimurium,
Staphylococcus aureus and Cl. perfringens. L. acidophilus
produces various bacteriocins and antibacterial substances
such as Lactocidin, Acidolin, Acidophilin, Lactacium-B
and inhibitory protein. Similarly, Bifidobacterium produces
Bidolin and Bilong, which inhibit several pathogenic
bacteria (Shah, 1999).
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3.2. Effectiveness against diarrhoea

A major problem associated with antibiotic treatment is
appearance of diarrhoea, often caused by Cl. difficile. This
organism is found in small numbers in the healthy
intestine, but disruption of indigenous microora due to
antibiotic treatment leads to an increase in their number
and toxin production, which causes the development
of diarrhoea. Treatment with metonidazole or vancomycin
is usually effective but recurrences are common. Probiotics
have proved to be useful as a prophylactic regimen
with antibiotic-associated diarrhoea as well as for treatment after onset of antibiotic induced diarrhoea. A daily
dose of Lactobacillus GG has been found to be effective
in termination of diarrhoea. Studies with a yeast preparation containing S. cerevisiae Boulardii has also been
effective in treatment of Cl. difficile related colitis (Shah,
2004, 2006b).
Rotavirus is one of the most common causes of acute
diarrhoea in children worldwide. During diarrhoeal stage
of infection, the permeability of gut epithelial cells is
increased to intact proteins. Probiotics are claimed to
shorten duration of rotavirus diarrhoea in children
(Saavedra, Bauman, Oung, Perman, & Yolken, 1994).
The strongest evidence of a benecial effect of dened
strains of probiotics has been established using
L. rhamnosus GG and B. lactis Bb-12 (now reclassied as
B. animalis Bb-12) for prevention and treatment of
diarrhoea and acute diarrhoea in children mainly caused
by rotaviruses. Selected probiotic strains are also effective
against antibiotic-associated diarrhoea. Certain probiotic
strains can inhibit the growth and adhesion of a range of
enteropathogens. Studies have indicated benecial effects
against pathogens such as Sal. typhimurium and Sal.
enteriditis. B. longum SBT-2828 has shown inhibition of
enterotoxigenic Escherichia coli. A pediatric beverage
containing a mix of B. animalis, L. acidophilus, and
L. reuteri has been found to be useful in the prevention
of rotavirus diarrhoea (Guandalini et al., 2000).
L. rhamnosus GG has been reported to be more effective
in treatment of rotavirus diarrhoea than preparations
containing Str. thermophilus and L. delbrueckii ssp.
bulgaricus. L. reuteri has also been effective in shortening
duration of rotavirus diarrhoea. It reduces the duration of
diarrhoea in children suffering from rotavirus diarrhoea.
Treatment with Lactobacillus GG was associated with
enhancement of IgA-specic antibody-secreting cells to
rotavirus and serum IgA antibody level.
There is also strong evidence that probiotic strains can
prevent travellers diarrhoea (Hilton, Kolakowski, Singer,
& Smith, 1997), which is caused by bacteria, particularly
enterotoxigenic E. coli. Several studies have been carried
out to assess the effects of probiotic preparations as
prophylaxis for travellers diarrhoea; however, the results
have been conicting. In one study, Danish tourists on
a 2-week trip to Egypt were given a mixture of live
freeze-dried preparation of L. acidophilus, B. animalis,
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L. delbrueckii ssp. bulgaricus and Str. thermophilus at a

daily dose of 109 cfu. The administration of probiotic
preparation reduced the frequency of diarrhoea. A similar
study conducted with Finnish tourists using a lyophilized
preparation of Lactobacillus GG also showed a reduction
in the occurrence of travellers diarrhoea. On the other
hand, Katelaris, Salam, and Farthing (1995) and de dios
Pozo-Olano, Warram, Gomez, and Cacazos (1978) have
found no effect in people suffering from travellers
diarrhoea when L. fermentum KLD L. acidophilus and
L. bulgaricus were given in separate studies.
Yoghurt containing B. longum was found to be effective
in reducing the course of erythromycin induced diarrhoea.
Faecal counts of Lactobacillus GG indicated that the
organisms colonized the intestine despite erythromycin
treatment. Probiotic reparations containing 4 109 cfu of
B. animalis Bb-12 and L. acidophilus La-5 has shown
similar results when volunteers received ampicillin along
with probiotic preparation. Several studies have shown a
reduction in diarrhoea in subjects taking S. cerevisiae
Boulardii during the period of antibiotic treatment (Shah,
2004, 2006a).
3.3. Improvement in lactose metabolism
Relief of the symptoms of lactose malabsorption is
probably the most widely accepted health benet of
probiotic organisms. Lactose malabsorption is a condition
in which lactose, the principal carbohydrate of milk, is not
completely hydrolysed into its component monosaccharides, glucose and galactose. Since lactose is cleaved into its
constituent monosaccharides by the enzyme b-D-galactosidase, lactose malabsorption results from a deciency of this
enzyme. Lactose malabsorbers often complain of gastric
distress after consuming fresh, unfermented milk or milk
products due to the formation of hydrogen gas by
microbial action on undigested lactose in the gut (Shah,
1993; Shah, Fedorak, & Jelen, 1992).
The traditional cultures used in making yoghurt (i.e.,
L. delbrueckii ssp. bulgaricus and Str. thermophilus) contain
substantial quantities of b-D-galactosidase (Shah, 2000c),
and so both yoghurt and probiotic yoghurt are tolerated
well by lactose malabsorbers. However, reduced levels of
lactose in fermented products due to partial hydrolysis of
lactose during fermentation are only partly responsible for
this greater tolerance for yoghurt. The slower gastric
emptying of both semi-solid and pasteurized yoghurt
results in better absorption of lactose (in the latter, enzyme
activity and bacteria are destroyed due to heat treatment;
Shah et al., 1992).
3.4. Antimutagenic properties
An antimutagenic effect of fermented milks has been
detected against a range of mutagens and promutagens in
various test systems based on microbial and mammalian
cells. Probiotic organisms are reported to bind mutagens
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to the cell surface (Orrhage, Sillerstrom, Gustafsson,

Nord, & Rafter, 1994). Probiotic bacteria are reported
to reduce faecal enzymatic activities including b-glucuronidase, azoreductase, and nitroreductase, which are
involved in activation of mutagens (Goldin & Gorbach,
1984b).
Lankaputhra and Shah (1998) studied the antimutagenic
activity of organic acids produced by probiotic bacteria
against several mutagens and promutagens. The TA-100
mutant of Sal. typhimurium (His) strain was used as a
mutagenicity indicator organism. The mutagenicity test
was carried out using the Ames Salmonella test. In their
study, butyric acid showed a broad-spectrum antimutagenic activity against all mutagens or promutagens studied
and live bacterial cells showed higher antimutagenicity
than killed cells. Inhibition of mutagens and promutagens
by probiotic bacteria was permanent for live cells and
temporary for killed cells. The results emphasized the
importance of consuming live probiotic bacteria and of
maintaining their viability in the intestine to provide
efcient inhibition of mutagens. Table 3 summarizes
studies pertaining to antimutagenic properties of functional
microorganisms.
3.5. Anticarcinogenic properties
Bacteria and metabolic products such as genotoxic
compounds (nitrosamine, heterocyclic amines, phenolic
compounds, and ammonia) are responsible for colorectal
cancer. The consumption of cooked red meat, especially
barbequed meat, and low consumption of bre are
reported to play a major role in causing colorectal cancer.
The colonic ora are also reported to cause carcinogenesis
mediated by microbial enzymes such as b-glucuronidase,
azoreductase, and nitroreductase, which convert procarcinogens into carcinogens.
Certain strains of L. acidophilus and Bifidobacterium spp.
are reported to decrease the levels of enzymes such as
b-glucuronidase, azoreductase, and nitroreductase responsible for activation of procarcinogens and consequently decrease the risk of tumour development (Yoon,
Benamouzig, Little, Francois-Collange, & Tome, 2000).
Short chain fatty acids produced by L. acidophilus and
Bifidobacterium, L. plantarum and L. rhamnosus are
reported to inhibit the generation of carcinogenic products
by reducing enzyme activities (Cenci, Rossi, Throtta, &
Caldini, 2002).
The anticarcinogenic effect of probiotic bacteria is
reported to be due to the result of removal of sources of
procarcinogens (or the enzymes that lead to their formation) improvement in the balance of intestinal microora,
normalized intestinal permeability (leading to prevention
or delaying of toxin absorption), strengthening of intestinal
barrier mechanisms, and activation of non-specic cellular
factors (such as macrophages and natural killer cells) via
regulation of g-interferon production. Orally administered
Bifidobacterium is also reported to play a role in increasing
production of IgA antibodies and functions of Peyers

patch cells (Singh et al., 1997). Table 4 summarizes studies
pertaining to anticarcinogenic properties of functional
microorganisms.
3.6. Reduction in serum cholesterol
The level of serum cholesterol is a major factor for
coronary heart disease, and elevated levels of serum
cholesterol, particularly LDL-cholesterol, have been linked
to an increased risk (Liong & Shah, 2006). There is a high
correlation between dietary saturated fat or cholesterol
intake and serum cholesterol level. Feeding of fermented
milk containing very large numbers of probiotic bacteria
(109 bacteria g1) to hypercholesterolaemic human subjects has resulted in lowering cholesterol from 3.0 to
1.5 g L1.
Probiotic bacteria are reported to de-conjugate bile salts:
deconjugated bile acid does not absorb lipid as readily as
its conjugated counterpart, leading to a reduction in
cholesterol level. L. acidophilus is also reported to take
up cholesterol during growth and this makes it unavailable
for absorption into the blood stream (Klaver & Meer,
1993). Studies showing reduction in serum cholesterol are
summarized in Table 5.
3.7. Helicobacter pylori infection
Helicobacter pylori is a pathogenic bacterium that causes
peptic ulcers, type B gastritis and chronic gastritis and is
normally present in the stomach as an opportunistic
pathogen without causing any symptoms (Armuzzi et al.,
2001; Sakamoto et al., 2001).
Antibiotic treatments can successfully eradicate
H. pylori. However, antibiotics often cause side effects
and make the bacteria more antibiotic resistant. Probiotic
organisms do not appear to eradicate H. pylori, but they
are able to reduce the bacterial load in patients infected
with H. pylori. L. johnsonii La1 and L. gasseri OLL2716
have been found to reduce H. pylori colonization and
inammation (Felley et al., 2001). Similarly, L. casei
Shirota and L. acidophilus are reported to inhibit the
growth of H. pylori (Cats et al., 2003). Studies showing
probiotic micro-organisms and H. pylori infection are
3.8. Inflammatory bowel disease
Inammatory bowel disease (ulcerative colitis and
Crohns disease) is related to the intestinal microora.
Symptoms of inammatory bowel disease include a
disturbance in bowel habits and mucosal inammation.
In the intestine of people with inammatory bowel disease
the numbers of Lactobacillus and Bifidobacterium are lower
and those of coccoids and anaerobes are higher. Probiotics
do not cure the disease, but once patients are in remission
through treatment with corticosteroids, some probiotics
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Table 3
Antimutagenic properties of functional microorganisms
Microorganism
Antimutagenic activity
References
L. acidophilus strains
Microbial binding leading to inhibition of mutagens and promutagens

such as 4-nitroquinoline-N0 -oxide, 2-nitrouorene and benzopyrene.
Ayebo et al. (1982)
L. acidophilus 2400, 2401, 2404, 2405, 2409,

2415; B. bifidum 1900, 1901, 1912, 1920, 1930
and 1941
L. casei CRL 431
Antimutagenic activity of organic acids produced by probiotic bacteria

against mutagens and promutagens such as 2-nitroourene, aatoxin-B,
and 2-amino-3-methyl-3H-imidazoquinoline.
The immune cells activated after oral L. casei administration to BALB/c
mice were those of the innate immune response (with an increase in the
specic markers of these cells, CD-206 and TLR-2), with no
modication in the number of T cells.
Lankaputhra and Shah

(1998)
L. rhamnosus GG
Inuenced intestinal physiology either directly or indirectly through

modulation of the endogenous ecosystem or immune system.
Marteau et al. (2001)
L. acidophilus (LAFTIs L10); B. lactis (LAFTI

B94)
Synbiotic combinations in regulating the consequences of carcinogeninduced damage to colonic epithelial cells in male Sprague-Dawley rats.
Le Leu et al. (2005)
L. acidophilus (SBT0274, SBT1703, SBT10239,

SBT10241); B. longum (SBT 2928)
Exhibited a high percentage of antimutagenicity and binding in vitro on

amino acid pyrolysates using a streptomycin-dependent (SD510) strain
of Sal. typhimurium TA 98.
Sreekumar and Hosono

(1998)
L. bulgaricus 291; Str. thermophilus F4, V3; B.

longum BB536
Clear evidence for DNA-protective effects of lactobacilli used for

yoghurt production against DNA damage caused by HCAs in organs
which are targets of tumor induction by 1-methyl-3-nitro-1nitrosoguanidine, 1,2-dimethylhydrazine, N-methyl-N-nitrosourea and
azoxymethane and also reduce chemically induced-DNA migration and
pre-carcinogenic lesions in colon cells of male Fischer 344 rats.
Zsivkovits et al. (2003);

Wollowski et al. (2001)
Lactobacillus GG; L. delbrueckii subsp.

rhamnosus (LGG); B. lactis Bb12
The groups treated with probiotics, the proportion of cancers relative to

the total number of tumours in the same groups was signicantly lower
(P 0.04) than in untreated male F344 rats suggesting that the possible
protective effect of probiotics is restricted to malignant tumours.
Femia et al. (2002)
L. helveticus L89
Antimutagenic compounds were produced in milk during fermentation

by L. helveticus, and the release of peptides was one possible
contributing mechanism. However, milk fermented by a non-proteolytic
variant of the same strain showed no inhibitory effects on 4nitroquinoline-N0 -oxide (4-NQO).
Matar et al. (1997)
B. infantis CCRC 14633, B. longum B6,

L. acidophilus CCRC 14079 and Str.
thermophilus CCRC 14085
Unfermented soymilk exerted lower antimutagenic activity against 3, 20 dimethyl-4-amino-biphenyl (DMAB) than 4-nitroquinoline-N-oxide (4NQO), the fermented soymilk, showed a higher antimutagenic activity
against DMAB than 4-NQO. Soymilk fermented with both Str.
themophilus and B. infantis simultaneously exhibited the highest
antimutagenicity of 85.07% and 85.78%, respectively, against 4-NQO
and DMAB.
Hsieh and Chou (2006)
L. acidophilus LA 106
The milk cultured with L. acidophilus LA 106 (LA2) showed the highest
inhibition of 77% against the mutagenicity of N-methyl-N-nitro-Nnitrosoguanidine among the 71 strains tested.
Hosoda et al. (1992)
Probiotic bacterium Ent. faecium M-74
Exerted different antimutagenic activity against ooxacin-, N-methyl,

N0 -nitro-N-nitrosoguanidine- and sodium 5-nitro-2-furylacrylateinduced mutagenicity in Sal. typhimurium assay depending on the
presence (+Se) or absence of disodium selenite pentahydrate (-Se). The
antimutagenicity of MRS(+Se) extract was higher than that of MRS(Se) extract. Selenium also enhanced the antimutagenic effect of both live
and killed cells of Ent. faecium M-74, respectively.
Belicova et al. (2004)
can prolong the remission period, thus reducing the

incidence of relapse and the use of corticosteroids. This
improves the quality of life of patients. Studies showing
probiotic micro-organisms and inammatory bowel disease
are summarized in Table 7.
Galdeano and Perdigon

(2006)
3.9. Immune system stimulation

The intestine is the bodys largest immune organ and the
intestinal microora and the metabolic activity of the
intestine is equivalent to that of the liver. Probiotics may
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Table 4
Probiotic microorganisms and their anticarcinogenic properties
Microorganisms
Anticarcinogenic function
References
L. acidophilus NCFM
Rats consuming a meat-based diet showed a lower incidence of colon

cancer after a 20-wk experimental period, implying that the NCFM
supplement increased the latency period for colon cancer in rats.
Administration of NCFM along with antibiotics also decreased colon
tumours. NCFM fed rats had a signicantly lower level of free amines in
the faeces.
Goldin and Gorbach

(1980, 1984a, c).
L. acidophilus NCFM
Using human subjects, daily consumption of milk containing NCFM

resulted in a 2- to 4-fold reduction in the activity of faecal enzymes, X glucuronidase, nitroreductase, and azoreductase.
Goldin and Gorbach

(1984b, c)
L. bulgaricus; Str. thermophilus
Ingestion of viable probiotics led to anticarcinogenic effects, through

detoxication of genotoxins in the gut of rats.
Wollowski et al.
(2001a, b)
L. bulgaricus; Str. thermophilus
Possibly inuenced metabolic, immunologic, and protective functions in

the colon.
Kasper (1996)
Lactobacillus and Bifidobacterium; cellular

components and metabolites of LAB
Limits DNA damage in colon cells (antigenotoxicity).
Pool-Zobel et al. (1993,

1996); Wollowski
(1998); Ji (1997)
Bifidobacterium fermented milk; fermented milk

with L. acidophilus, B. bifidum, Lc. lactis ssp.
lactis, Lc. lactis ssp. cremoris
Procarcinogenic enzyme activity decreased: b-glucuronidase,

nitroreductase, azoreductase and detoxifying enzyme activity increased.
Benno and Mitsuoka

(1992); Bouhnik et al.
(1996)
L. acidophilus; Lc. lactis ssp. cremoris,
Binding of mutagens.
Orrhage et al. (1994);

Morotomi and Mutai
(1986)
B. lactis; L. gasseri
Released bioactive hydroxycinnamic acids in the human colon which

showed anticarcinogenic properties both in vitro and in animal models.
Couteau, et al. (2001)
L. acidophilus
Decreased polyps, adenomas and colon cancer in experimental animals.
Gorbach et al. (1987)
L. acidophilus 145; B. longum 913
Reduction of the risk of colon cancer by inhibiting carcinogen-induced

DNA damage in animals.
Moschner et al. (2004)
directly or, by changing the composition or activity of the

intestinal microora, indirectly inuence the bodys immune function (Marteau et al., 1997). Probiotic cultures
produce g-interferon by T-cells and stimulate cytokines as
represented by TNF-a (tumour necrosis factor) and IL-6
and IL-10 (interleukines 6 or 10). Immunomodulation by
L. acidophilus and Bifidobacterium has been observed, in
particular IgA levels and non-specic immunity. Ingestion
of probiotic yoghurt has been reported to stimulate
cytokine production in blood cells and enhance the
activities of macrophages. Studies showing probiotic
micro-organisms and immune system stimulation are
4. Prebiotics and synbiotics
To maximize effectiveness of bidus products, prebiotics
are used in probiotic foods. A prabiotic is a non-digestible
food that benecially affects the host by selectively
stimulating the growth and/or activity of one or a limited
number of bacteria in the colon (Shah, 2004, 2006b).
Some oligosaccharides, due to their chemical structure,
are resistant to digestive enzymes and therefore pass into
the large intestine where they become available for
fermentation by saccharolytic bacteria. Compounds that

are either partially degraded or not degraded by the host
and are preferentially utilized by Bifidobacterium as a
carbon and energy sources are referred to as bidogenic
factors. Some bidogenic factors that are of commercial
signicance include fructo-oligosaccharides, lactose derivatives such as lactulose, lactitol, galacto-oligosaccharides,
and soyabean oligosaccharides. Resistant starch and nonstarch oligosaccharides are classied as colonic foods, but
not as prebiotics, because they are not metabolized by
certain benecial bacteria (Shah, 2004).
The products that contain both prebiotics and probiotics
are referred to as synbiotics. Synbiotics are a combination
of the effects of probiotics and prebiotics to produce health
enhancing functional food ingredients. Japan is the world
leader in probiotic and prebiotic products. The majority of
yoghurts marketed in Australia, USA and Europe in recent
years contain one or more species of probiotic bacteria and
some form of prebiotics (Shah, 2000a).
5. Alternate products for incorporating probiotics
To realize health benets, probiotic bacteria must be
viable and must be available in a high concentration,
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Table 5
Probiotic microorganisms and reduction in serum cholesterol
Microorganisms
Probiotic function
References
L. acidophilus
Lowered serum cholesterol levels.
Ouwehand et al. (2002)

1
L. acidophilus; L. casei ASCC 1520, ASCC

1521, ASCC 292, ATCC 15820, and
L. acidophilus ATCC 4962
Highest in vitro cholesterol assimilation of more than 25 mg mL

cholesterol in the presence of cholic acid, compared to other different bile
media.
Liong and Shah (2005)
Human strain of Ent. faecium
29 men receiving milk fermented with a human strain of E. faecium

(1081011 cfu L1) led to a decrease in serum cholesterol by
0.370.41 mmol L1 after 6 wk, whereas consumption of the placebo had
no effect.
Agerbaek, Gerdes, and

Richelsen (1995)
Enterococcus group of 87 men and women had a signicantly larger

decrease in serum LDL concentrations decreased throughout the study,
than the placebo-group at weeks 4 and 12 (Po0.05).
Richelsen et al. (1996)
Ent. faecium (Gaio)
Was found to be effective in reducing both total and low density

lipoprotein cholesterol by 4% and 5%, respectively, compared with the
control group.
Agerholm-Larsen, Bell,
Grunwald, and Astrup
(2000)
L. casei TMC 0409
In a single blind parallel study, subjects consuming fermented milk

(200 mL day1) showed signicant increases of high density lipoprotein
cholesterol, compared with the pre-intervention levels after four weeks
supplementation. The levels of triglycerides were also reduced signicantly
in subjects receiving the fermented milk.
Kawase et al. (1999)
Str. thermophilus TMC 1543
In a single blind parallel study, subjects consuming fermented milk

(200 mL day1) showed signicant increases of high density lipoprotein
cholesterol, compared with the pre-intervention levels after eight weeks
supplementation. The levels of triglycerides were also reduced signicantly
in subjects receiving the fermented milk.
Kawase et al. (1999)
B. longum 913; L. acidophilus 145
Consumption of 300 g yoghurt supplemented with the 2 microrganisms for

seven weeks increased high density lipoprotein concentration by
0.3 mmol L1 (p 0.002) and decrease ratio of low to high density
lipoprotein from 3.24 to 2.48 (p 0.001).
Kiebling et al. (2002)
L. gasseri SBT0270, SBT0274
Exerted hypocholesterolaemic effect in rats fed a diet high in cholesterol

through deconjugation of bile salts.
Usman and Hosono

(2000)
L. reuteri CRL 1098 (104 cells d1)
Caused a 40% reduction in triglycerides and a 20 increase in the ratio of

high density lipoprotein to low density lipoprotein without bacterial
translocation of the native microora into the spleen and liver of Swiss
Albino mice.
Taranto et al. (1998)
B. longum BL1
Led to a signicant lowering of the serum concentrations of total

cholesterol, low-density lipoprotein cholesterol, and triglycerides in milk
products compared with the control, while no change in high-density
lipoprotein cholesterol concentration was observed.
Xiao et al. (2003)
L. brevis NR1C1684; Ent. faecalis
Assimilated more cholesterol (in vivo) than the average of the other strains
in the media with 0.2 and 0.4% (wt/vol) oxgall, respectively.
Pereira and Gibson

(2002)
typically 106 cfu g1 of a product. Despite the importance

of viability, studies have shown low populations of
probiotic bacteria in probiotic foods (Anon, 1992; Shah,
Lankaputhra, Britz, & Kyle, 1995; Shah, Ali, & Ravula,
2000). It is questionable whether such products can provide
the claimed benets if the populations of probiotic bacteria
are low. Yoghurt is considered the most important carrier
of probiotic bacteria. However, a number of factors affect
the loss of viability of probiotic organisms in yoghurt,
including acidity of products, acid produced during
refrigerated storage (also known as post-acidication),
level of oxygen in products and oxygen permeation

through the package, sensitivity to antimicrobial substances produced by starter bacteria and lack of nutrients
in milk (Dave & Shah, 1997a, b; Lankaputhra & Shah,
1995, 1997; Shah, 2000a; Tamime, Saarela, Sandergaard,
Mistry, & Shah, 2005).
A number of food products including probiotic yoghurt,
ice cream, frozen fermented dairy deserts, and freeze-dried
yoghurt (Capela, Hay, & Shah, 2006) have been employed
as alternate delivery vehicles for probiotics. But, due to the
presence of high oxygen content (Lankaputhra & Shah,
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Table 6
Probiotic microorganisms and Helicobacter pylori infection
Microorganisms
Probiotic function
References
L. salivarius
Suppressed and eradicated H. pylori in tissue cultures and animal models

by lactic acid secretion.
Aiba et al. (1998)
L. gasseri OLL2716(LG21)
Signicant improvement on 31 subjects infected with H. pylori and

reduced gastric mucosal inammation following LG21 treatment.
Sakamoto et al. (2001)
Bac. subtilis 3
Inhibited H. pylori, the inhibitory zone for each of the 21 strains of H.

pylori isolates ranged from 10 to 16 mm.
Pinchuk et al. (2001)
Bac. clausii
Bacteriotherapy reduced the incidence of the most common side-effects

related to anti-H. pylori antibiotic therapy compared with placebo.
Nista et al. (2004)
L. rhamnosus GG, L. rhamnosus LC705;

B. breve Bb99; Propionibacterium
freudenreichii ssp. shermanii JS
Probiotic group showed less treatment-related symptoms as measured by

the total symptom score change (P 0.038) throughout the H. pylori
eradication therapy in contrast to the placebo group.
Myllyluoma et al. (2005)
Ent. faecium; Bac. subtilis; Bifidobacterium
Produced heat-stable proteinaceous compounds capable of inhibiting the

growth of both antibiotic-resistant and -sensitive strains of H. pylori.
Tsai et al. (2004); Pinchuk

et al. (2001); Collado et
al. (2005)
L. acidophilus LA5+B. lactis Bb12
Increased eradication of H. pylori among 160 dyspeptic subjects in 4 weeks

with combined use of certain antibiotics.
Sheu et al. (2002)
L. reuteri ATCC 55730 (108 CFU)
Probiotic supplemented children had a signicant reduction of GSRS

score during eradication therapy compared to those receiving placebo.
Lionetti et al. (2006)
L. acidophilus strain LB (lyophilized)
1-week standard therapy increased eradication rate of H. pylori in active

group of 120 patients.
Canducci et al. (2000)
L. casei strain Shirota
There was a trend towards suppressive effect in an active group of 20

patients.
There was reduced density of H. pylori, reduced inammation and gastritis
activity among 52 patients.
Cats et al. (2003)
L. acidophilus NAS
Eradication of H. pylori in six of 14 patients after 8 weeks of treatment.
Mrda et al. (1998)
L. casei subsp. rhamnosus (GG); S.

cerevisiae Boulardii; L. acidophilus; B. lactis
Probiotic preparations supplementing a standard antiH. pylori regimen

were associated with lower incidence of self-reported side effects and with
better treatment tolerability compared to placebo.
Cremonini et al. (2002)
L. reuteri strains (JCM1112, JCM1081,

JCM1084 JCM2762, JCM2763 and
JCM2764)
Inhibition by selected L. reuteri strains helped to prevent infection in an

early stage of colonization in H. pylori leading to a proposal that L. reuteri
strains sharing glycolipid specicity with H. pylori have a potential as
probiotics.
Mukai et al. (2002)
L. johnsonii La1
1997) in ice cream type products and injury due to freezing

and freeze drying, many of the above mentioned products
have failed to successfully deliver the required level of
viable cells of probiotics. Cheese-based dips could be a
delivery vehicle for probiotic bacteria because of its stable
pH, the buffering capacity of ingredients used and the
presence of prebiotics (Tharmaraj & Shah, 2004).
Other foods such as Cheddar cheese have also been
studied as carriers of probiotic microorganisms. Cheeses
have a number of advantages over fresh fermented
products such as yoghurt as a delivery system for viable
probiotic to gastrointestinal tract as they tend to have
higher pH, more solid consistency and relatively higher fat
content. These offer protection to probiotic bacteria during
storage and passage through the gastrointestinal tract.
Cheeses also have higher buffering capacity than yoghurt.
Cheddar cheeses, however, have long ripening time hence
Felley et al. (2001)
development of probiotic Cheddar cheese requires a careful

examination of the suitability of particular strain(s) to
maintain viability throughout the ripening and shelf life
(Ong, Henriksson, & Shah, 2006). Two Cheddar cheeses
TM
containing the probiotic DR20 were launched by Mainland (Fonterra) in Australia in 2002 under the name Inner
Balance.
Another product, which has received much attention, is
soy based isoavone phytoestrogens, found abundantly in
soybeans, are an isomeric family of di-phenolic compounds
with structural and functional similarities to human
estrogens. Soybeans and non-fermented soy foods (including soy extract) contain 8095% of their isoavones as
glucoside conjugates, which are biologically inactive and
non-bioavailable (Tsangalis, Ashton, McGill, & Shah,
2002). The biologically active (estrogen-like) and bioavailable aglycone forms of daidzein, genistein and glycitein are
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Table 7
Probiotic microorganisms and inammatory bowel disease
Microorganisms
Probiotic function
References
Ent. faecium
Decreased duration of acute diarrhoea from gastroenteritis.
L. acidophilus
Signicant decrease of diarrhoea in patients receiving pelvic irradiation.
L. plantarum
Especially effective in reducing inammation in inammatory bowel; e.g.,

enterocolitis in rats, small bowel bacterial overgrowth in children, pouchitis.
Schultz and Sartor (2000);

Vanderhoof (2000)
Reduced pain and constipation of irritable bowel syndrome. Reduced bloating,

atulence, and pain in irritable bowel syndrome in controlled trial.
Nobaek et al. (2000)
Shortened the duration of acute gastroenteritis.
Shortened acute diarrhoea.
Shornikova et al. (1997a,

1997b)
S. cerevisiae Boulardii (yeast)
Reduced recurrence of Cl. difficile diarrhoea.

Effects on Cl. difficile and Klebsiella oxytoca resulted in decreased risk and/or
shortened duration of antibiotic-associated diarrhoea. Shortened the duration of
acute gastroenteritis. Decreased only functional diarrhoea, but not any other
symptoms of irritable bowel syndrome.
Pochapin (2000)
B. bifidum; Str. thermophilus
Reduction of rotavirus shedding and episodes of diarrhoea in children in hospital.
Saavedra et al. (1994)
Ent. faecium PR88
Symptomatic improvement in 19 of the 28 patients with high volume diarrhoea

caused by food intolerance for twelve weeks and a signicant decrease in faecal
weight.
Hunter et al. (1996)
S. cerevisiae Boulardii; L.
rhamnosus GG
Helped prevent antibiotic-associated diarrhoea (AAD). S. cerevisiae Boulardii

appeared useful for Cl. difficile disease.
McFarland (2006)
L. reuteri
linked to the prevention and potential treatment of

hormone-dependent disorders, including osteoporosis,
cardiovascular disease and cancer (Tsangalis, Ashton,
Wilcox, Shah, & Stojanovska, 2005). Recent research has
shown that isoavone aglycones are absorbed faster and in
higher amounts in humans than their respective glucosides.
Intestinal microora, consisting predominantly of Bifidobacterium, are of signicant importance in hydrolysing
ingested isoavone glucosides into bioavailable, bioactive
aglycones (Tsangalis et al., 2005), as well as in converting
daidzein to the biologically potent equol. Fermentation of
plain soy extract with Bifidobacterium sp. is reported to
hydrolyse the isoavone glucosides into bioactive aglycones, increasing the concentration of aglycones from less
than 10% to approximately 50% of the total isoavone
content (Tsangalis et al., 2002).
5.1. Products based on bioactive peptides released from milk
proteins by proteolytic probiotics
The functionality of dairy proteins is further enhanced
upon liberation of bioactive peptides by proteolysis
(Gobbetti, Stepaniek, De Angelis, Corsetti, & Di Cagno,
2002). Proteolysis is performed by naturally occurring
enzymes in milk, starter cultures and the enzymes of the
digestive tract, resulting in release of many peptides with
different biogenic activities such as opioid, hypotensive,
immunomodulating, antithrombotic and antimicrobial
activities.
Dairy cultures used in production of fermented milk

products have appreciable proteolytic activity enabling
their rapid growth in milk. During fermentation, milk
proteins, namely caseins, undergo a slight proteolytic
degradation resulting in a number of potentially bioactive
peptides (Table 9). Strains of L. helveticus have been
identied as highly proteolytic and peptidolytic towards
caseins and their derivatives and, if used in fermentations,
they can produce products with a range of bioactivities
such as opioid and hypotensive activity (Matar, Amiot,
Savoie, & Goulet, 1996).
Another group of bioactive peptides, termed angiotensin
I-converting enzyme (ACE) inhibitors, have been extensively studied due to their hypotensive role (Conlin et al.,
2000). Milk proteins contain a number of ACE inhibiting peptides encrypted within their primary structures
(Donkor, Henriksson, Vasiljevic, & Shah, 2005). These
peptides are liberated by proteolytic action of extracellular
and intracellular enzymes of LAB proteolytic system.
Strains of L. helveticus appeared to be superior in regard
to production of ACE inhibitory peptides in comparison
with other species tested (Ashar & Chand, 2003). Several
commercial products containing highly proteolytic strains
of L. helveticus have been developed and marketed as
possessing hypotensive activity, including Calpiss and
Evoluss. Calpiss sour milk (Calpis Co. Ltd., Tokyo,
Japan), is prepared by fermenting milk using mixed culture
containing L. helveticus CM4 (CP790) and S. cerevisiae.
These organisms are responsible for the release of a range
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Table 8
Probiotic microorganisms and immune system stimulation
Microorganisms
Probiotic function
References
Lactobacillus strains
Microbial interference therapythe use of nonpathogenic bacteria to

eliminate pathogens and as an adjunct to antibiotics.
Improved mucosal immune function, mucin secretion and prevention of
disease.
Bengmark (2000)
L. acidophilus NCFM
Prevented urogenital infection with subsequent exposure to three pathogens

E. coli, Klebsiella pneumoniae, Pseudomonas aeruginosa.
Sanders and Klaenhammer

(2001)
L. plantarum
Positive effect on immunity in HIV+ children.
Walker (2000)
L. rhamnosus
Enhanced cellular immunity in healthy adults in controlled trial.
Tomioka et al. (1992)
S. cerevisiae Boulardii
In HIV associated acute diarrhoea, 56% of patients who were treated with
S.cerevisiae Boulardii had their symptoms resolved compared with only 6% of
placebo treated patients.
Saint Marc et al. (1999)
L. casei sp.; L. fermentum sp.
Can induce cytokine responses in human peripheral blood mononuclear cells.
Chen et al. (1999);

Miettinen et al. (1996)
L. salivarius strain
Produces a large amount of lactic acid and completely inhibits the growth of
H. pylori in a mixed culture, hence suppressing H. pylori, and reducing the H.
pylori-induced inammatory response.
Aiba et al. (1998)
L. acidophilus DDS-1
Has been shown to induce the production of IL-1a and TNF- a.
Rangavajhyala et al. (1997)
L. helveticus
Able to release peptide compounds that may have important implications for
the modulation of the cellular immune response.
Matar et al. (2001);

Leblanc et al. (2002)
L. acidophilus TMC 0356
Signicantly increased the production of IL-6, IL-10, IL-12, and TNF-a
Morita et al. (2002)
L. rhamnosus sp.; L. plantarum or

L. paracasei ssp. paracasei strains
Induced high levels of IL-10 in human blood mononuclear cells, or monocytes

and highest levels of IL-12 produced by L. paracasei subsp. paracasei strains,
implying its suitability to stimulate cell-mediated immunity.
Hessle et al. (1999)
L. casei Shirota
Induced a marked increase in the production of IL-12, probably by

macrophages, which in turn stimulated the production of IFN-g.
Kato et al. (1999)
Induced the production of several cytokines, such as IFN- g, IL-1b and TNFa in mice.
Matsuzaki (1998)
B. adolescentis; B. longum
Induced signicantly more pro-inammatory cytokine secretion of IL-12 and

TNF-a than did the infant-type bidobacteria, B. bifidum, B. breve, and B.
infantis.
He et al. (2002)
L. plantarum 299v
In the presence of the proinammatory cytokine TNF-a, exerted a protective

effect by downregulating IL-8 secretion in the human HT-29 colonic epithelial
cell line.
Mccracken et al. (2002)
L. casei DN-114 001, DN-114056,

ATCC-334; L. bulgaricus LB-10 strains
Normal colonic specimens have been obtained from Crohns disease (CD)
patients with neoplasm and inamed ileal specimens after being cultured with
either of these microorganisms.
Borruel et al. (2003)
L. johnsonii La1
Increases transforming growth factor beta mRNA in leukocyte-sensitized

Caco-2 cells.
Haller et al. (2000)
L. johnsonii La1; B. bifidum Bb12

strains
In healthy volunteers receiving a fermented milk product supplemented with

either bacteria for 3 weeks, phagocytosis of E. coli sp. by leukocytes isolated
from the blood was enhanced.
Schiffrin et al. (1995, 1997)
L. casei Shirota; B. breve YIT4064

strains
In mice, oral administration of either bacteria activated the humoral immune

system.
Yasui et al. (1999)
L. casei ssp. rhamnosus GG
Prevents cytokine-induced apoptosis in intestinal epithelial cell lines in culture

by activating the anti-apoptotic Akt/protein kinase B, and by inhibiting the
pro-apoptotic p38/mitogen-activated protein kinase by stimulating the
production of TNF-a, IL-1b, IL-1a, or INF-g.
Yan and Polk (2002)
MacFarlane and
Cummings (2002)
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Table 9
Some examples of the identied bioactive peptides in fermented milk and their physiological activitya
Sequence
Microbial agent
Precursor
Bioactivity
Val-Pro-Pro
L. helveticus CM4 &
b- & k-casein
Hypotensive
Ile-Pro-Pro
Val-Pro-Pro
S. cerevisiae
L. helveticus
b- & k-casein
Hypotensive
Ile-Pro-Pro
Asn-Leu-His-Leu-Pro-
LBK16H
L. helveticus NCC
b-casein
ACE inhibition
Leu-Pro-Leu-Leu
Tyr-Pro-Phe-Pro-Glu-
2765
L. helveticus NCC
b-casein
Opioid
Pro-Ile-Pro-Asn
Tyr-Pro
2765
L. helveticus CPN4
caseins
ACE inhibition
Leu-Asn-Val-Pro-Gly-
L. delbrueckii ssp.
b-casein
ACE inhibition
glu-Ile-Val-Glu
Asn-Ile-Pro-Pro-LeuThr-Glu-Thr-Pro-Val
bulgaricus SS1
Lc. lactis ssp.
cremoris FT4
b-casein
ACE inhibition
Adapted from Vasiljevic and Shah (2007).
of potent bioactive peptides including two tripeptides, ValPro-Pro and Ile-Pro-Pro (Nakamura et al., 1995; Vasiljevic
& Shah, 2007).
6. Conclusions
Probiotic products containing L. acidophilus, Bifidobacterium spp. and L. casei are becoming increasingly popular. Other probiotic organisms including Ent. faecium,
S. cerevisiae Boulardii and Propionibacterium have potential to be used in probiotic products. Several health benets
have been claimed for probiotic bacteria. Yoghurt is the
most important delivery vehicle for probiotic organisms.
Cheddar cheese, dips and spreads are becoming popular as
alternate products for incorporation of probiotics. Proteolytic strains of probiotic bacteria are used to release
bioactive peptides such as ACE-inhibitor peptides for
further improving the health benets of probiotic foods.
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ARTICLE IN PRESS

International Dairy Journal 17 (2007) 12621277

Functional cultures and health benets

E-mail address: Nagendra.Shah@vu.edu.au.

At the beginning of this century, Nobel Laureate Elie

longevity to ingestion of bacteria present in yoghurt

1900s that scientists began to investigate the reasons for

LA-1/LA-5 (Chr. Hansen)

Bifidobacterium are normal inhabitants of the human

ATCC 15703, 94-BIM

more pH stable than L. acidophilus and produces

3.2. Effectiveness against diarrhoea

L. delbrueckii ssp. bulgaricus and Str. thermophilus at a

N.P. Shah / International Dairy Journal 17 (2007) 12621277

to the cell surface (Orrhage, Sillerstrom, Gustafsson,

production of IgA antibodies and functions of Peyers

Microbial binding leading to inhibition of mutagens and promutagens

Ayebo et al. (1982)

L. acidophilus 2400, 2401, 2404, 2405, 2409,

Antimutagenic activity of organic acids produced by probiotic bacteria

Lankaputhra and Shah

Inuenced intestinal physiology either directly or indirectly through

Marteau et al. (2001)

L. acidophilus (LAFTIs L10); B. lactis (LAFTI

Le Leu et al. (2005)

L. acidophilus (SBT0274, SBT1703, SBT10239,

Exhibited a high percentage of antimutagenicity and binding in vitro on

Sreekumar and Hosono

L. bulgaricus 291; Str. thermophilus F4, V3; B.

Clear evidence for DNA-protective effects of lactobacilli used for

Zsivkovits et al. (2003);

Lactobacillus GG; L. delbrueckii subsp.

The groups treated with probiotics, the proportion of cancers relative to

Femia et al. (2002)

Antimutagenic compounds were produced in milk during fermentation

Matar et al. (1997)

B. infantis CCRC 14633, B. longum B6,

Hsieh and Chou (2006)

Hosoda et al. (1992)

Probiotic bacterium Ent. faecium M-74

Exerted different antimutagenic activity against ooxacin-, N-methyl,

Belicova et al. (2004)

can prolong the remission period, thus reducing the

Galdeano and Perdigon

3.9. Immune system stimulation

N.P. Shah / International Dairy Journal 17 (2007) 12621277

Rats consuming a meat-based diet showed a lower incidence of colon

Goldin and Gorbach

Using human subjects, daily consumption of milk containing NCFM

Goldin and Gorbach

L. bulgaricus; Str. thermophilus

Ingestion of viable probiotics led to anticarcinogenic effects, through

L. bulgaricus; Str. thermophilus

Possibly inuenced metabolic, immunologic, and protective functions in

Lactobacillus and Bifidobacterium; cellular

Limits DNA damage in colon cells (antigenotoxicity).

Pool-Zobel et al. (1993,

Bifidobacterium fermented milk; fermented milk

Procarcinogenic enzyme activity decreased: b-glucuronidase,

Benno and Mitsuoka

L. acidophilus; Lc. lactis ssp. cremoris,

Orrhage et al. (1994);