Appraisal of Probiotics and Prebiotics in Gastrointestinal Infections

Article ID: WMC003796
ISSN 2046-1690
Appraisal of Probiotics and Prebiotics in

Gastrointestinal Infections
Corresponding Author:
Dr. Asit R Ghosh,
Senior Professor & Assistant Director, Centre for Infectious Diseases & Control, School of Biosciences and
Technology, VIT University, , Centre for Infectious Diseases & Control, School of Biosciences and Technology,
VIT University, Vellore, INDIA, 632014 - India
Submitting Author:
Dr. Asit R Ghosh,
Senior Professor & Assistant Director, Centre for Infectious Diseases & Control, School of Biosciences and
Technology, VIT University,, Centre for Infectious Diseases & Control, School of Biosciences and Technology,
VIT University, Vellore, INDIA, 632014 - India
Article ID: WMC003796

Article Type: Review articles
Submitted on:27-Oct-2012, 12:53:50 PM GMT
Published on: 29-Oct-2012, 07:51:37 PM GMT
Article URL: http://www.webmedcentral.com/article_view/3796

Subject Categories:GASTROENTEROLOGY
Keywords:Probiotics, Prebiotics, Synbiotics, Gastrointestinal infection, Curd, Diarrhea
How to cite the article:Ghosh AR. Appraisal of Probiotics and Prebiotics in Gastrointestinal Infections .
WebmedCentral GASTROENTEROLOGY 2012;3(10):WMC003796
Copyright: This is an open-access article distributed under the terms of the Creative Commons Attribution
License(CC-BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the
original author and source are credited.
Source(s) of Funding:
The project was carried out by the intramural funding which was supported for the promotion of science in the
VIT University, Vellore, India
Competing Interests:
There is no competing intersts
WebmedCentral > Review articles
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Appraisal of Probiotics and Prebiotics in

Gastrointestinal Infections
Author(s): Ghosh AR
Abstract
A probiotic is a viable microbial dietary supplement
that beneficially affects the host through its effects in
the gastrointestinal tract (GIT). Probiotics are widely
used to prepare fermented dairy and non-dairy
products. Several health-related effects associated
with the intake of probiotics, including alleviation of
lactose intolerance, immune enhancement, control of
different kinds of diarrhea and colon cancer etc. have
been reported in human studies. Prebiotics are
nondigestible food ingredients that benefit the host by
selectively stimulating the growth or activity of one or a
limited number of microorganisms in the colon. Work
with prebiotics has been limited, only several
oligosaccharides and inulin-type fructans have
generated some research-based effective data.
However, the common understanding about the utility
of prebiotics is that they benefit our intestinal
ecosystem, improve immunity and overall health. At
present, claims about reduction of disease risk are
only tentative and further research is needed. The
combination of probiotics and prebiotics in a synbiotic
has not also been studied well. This combination might
improve the survival of the bacteria crossing the upper
part of GIT, thereby enhancing their effect in the large
bowel. In addition, their effects might be additive or
even synergistic. Several research groups are evolved
in India to implement the age-old system into modern
practice. Fundamental research with clinical trials is
there with the growth of Probiotic market in India.
Present trends of research hopefully will ensure the
implementation of its potentials towards the benefit of
life extensively.
Review
General Concept:
About a century ago, India won her first Noble prize by
the work of Viswakavi Rabindranath Tagore in the
year 1913. In his several novels, he mentioned about
the curd or dahi or specially misti dahi and sketched a
character of a curd peddler, in: Dakghar (Post office).
Almost during the same period, Elie Metchnikoff
received Noble prize for his discovery of phagocytosis
in 1908, and devoted last decade of his life

investigating means of increasing human longivity and
advocating the consumption of lactic acid producing
bacteria (Shruthy et al., 2011). Again our Vedic
Sanskriti had recognized the role of diet in health and
nutrition and now after several thousand of years, we
are proving and improving the linkages among health,
nutrition and diet with science based investigation. The
usage of panchamrit in Hindu rituals is to be
considered as the oldest functional food or synbiotic
food in the history of mankind. The utility of curd has
been described in Rig-Veda also. The Dadhi made out
of cows milk has been described as a likeable food
not only for the humans but of gods as well. The
following mantra from Rig-Veda (10-179-3) aptly
describes the nutritional qualities of Dadhi or curd
(made from cows milk):
Shratam manya oodh nishrat magnow
sushraatam manye tadyate naviyah
madhyen dinasaya sevanasya dadhana pivender
vajrinpuru krijjushanah.
However, lack of written documents and scientific
evidence kept western world unaware and unnoticed
until the publication of book, Prolongation of life in
1907 by Elie Metchnikoff.
Dahi or Dadhi or Doi or Tahri or Perugu or Mosaru or

Thayir are the acronyms for curd or yogurt in India.
The Indian economy had been agriculture-based since
the Vedic civilization. Cow and land were the sources
of major economy. Almost all the oldest documents
and mythological inscriptions were cow-centric. Cow
milk and milk products are thus obviously and
intimately involved with Indian society. Right from the
day of Lord Krishna to the modern age, milk, and
thousands of milk-products like curd, cream, butter,
lassi, paneer, sandesh, rasogolla, ksheer; sreekhand
etc. are in common use regularly. Specially, curd is a
very essential and regular food item in India with
particular reference to south India. The curd is
prepared in India by natural contamination and
fermentation. Besides milk, other indigenous
fermented foods have been prepared and consumed
for thousands of years and are strongly linked to
culture and tradition. In the Indian subcontinent,
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making use of fermented food and beverages using

local food crops and other biological resources are
very common (Roy et al., 2004). But the nature of
products and the base material vary from region to
region. One can contemplate that people are using
microorganisms, unknowingly for varied purposes.
Further, such kind of undocumented knowledge of
traditional systems is in the danger of extinction due to
various causes. The contaminants may be yeast
or/and bacteria. The fermented food and beverages
contain microorganisms those may or may not be
beneficial to health, but are generally regarded as safe
(GRAS). Again, the beneficial microbes are called
probiotics with special characteristics. The metabolic
ingredients which support the growth of probiotics are
termed as prebiotics. Together probiotics and
prebiotics constitute the functional food, called
synbiotics (Bagad et al., 2012).
The scientific understanding of probiotics and their
potential for preventing and treating health conditions
is moving ahead. The effectiveness of probiotics is
strain-specific, and each strain may contribute to host
health through different mechanisms. Pathogen
inhibition by probiotics may provide significant human
health benefits. Many reports indicate that probiotics
can affect innate immunity and also protect against
pathogens by decreasing pathogenic adherence or by
production of acids or bacteriocins (Kumari et al.,
2011). The most usual application of probiotic
microorganisms is for the prevention or therapy of
gastro intestinal disorders such as irritable bowel
syndrome (Cui and Hu, 2012; Murakami et al., 2012),
colitis (Rodrigues et al., 2012), colon cancer (Denipote
et al., 2010; Wollowski et al., 2001) and most
importantly diarrhoea (Boyle et al., 2006; Cremonini
and Videlock, 2012). Several clinical trials have
evaluated their effective use in the prevention and
treatment of infectious gastro-intestinal (GI) diseases
or disturbances happened in the normal micro-flora.
The ideal probiotic is one that remains viable in
sufficient number by adhering to the intestinal
epithelium to confer a significant health benefit
(Kumari et al., 2011). In the last three decades,
scientists have gathered plenty of evidences of health
and nutritional benefits of probiotics. As a result many
global companies including India participated in the
manufacturing of several different nutraceuticals and
pharmaceuticals to offer health benefits to society.
2. Introduction to probiotics, prebiotics, synbiotics
Let food be thy medicine and medicine thy food, the
age old quote by Hippocrates is certainly the tenet of
today. The growing interest in understanding the role
of food in human health has moved from the primary
role of food as a source of energy to the more subtle

action of biologically active food components on
human health. Probiotics has been defined by an
expert committee as living organisms, which upon
ingestion exerts health benefits beyond inherent
general nutrition. FAO has defined it as live
microorganisms which when administered in adequate
amounts confer a health benefit on the host.
Probiotics commonly stem from the category of Lactic
acid bacteria (LAB). LAB are Gram positive, non-spore
forming, catalase negative, acid tolerant and strictly
fermentative with lactic acid as the major end product
during sugar fermentation (homo- or
hetero-fermentative). LAB with probiotic potentials are
known to exert positive influence on host health and
physiology. The physiological effects include the
production of antibacterial substances, maintenance of
healthy microflora, reduction of cholesterol level in the
blood (Starovoitova et al., 2012), stimulation of
immune functions and the removal of carcinogens
(Boyle et al., 2006; Rupa and Mine, 2012). At present
probiotic bacteria are widely used in human and
animal nutrition because they beneficially influence the
balance of the intestinal flora of the host (Kumari et al.,
2011). Implementation of probiotics is intended to
reduce the use of antibiotics, with a proven low risk of
inducing or being associated with the etiology of
disease (Szajewska, et al., 2006).
Mahatma Gandhi advocated the virtues of fermented
milk and milk products in his book The Diet Reform.
The therapeutic property of curd is due to the probiotic
bacteria present in them. Promising probiotic
microorganisms come under the genera Lactobacillus
and Bifidobacterium. In general, LAB are food-grade
organisms witnessing a long history of safe use and
are categorised as GRAS for human consumption. But
not all curd bacteria may have the probiotic potentials
and may not be as good as it is labeled with yogurt. To
address the fact that how far curds we consume are
probiotic, we performed a study for two years which
revealed that 10 of 20 samples (50%) had lactic acid
bacteria and only two of LAB positive curds (10%)
had the probiotic strains of Lactobacillus spp. Isolated
strains showed several characteristics of being a good
probiotic. Strains were acid resistant, bile salt tolerant,
antibacterial, and antagonistic by slow acidification
and antimicrobial production, and adherent (Shruthy et
al., 2011).
Dahi or curd is a regular food component of South
India and has been documented well for its beneficial
effects. It is the semisolid product obtained from
pasteurized or boiled cow/buffalo milk by souring
natural or otherwise by a harmless lactic acid or other
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bacterial culture. Unlike yoghurt which involves the

use of specific symbiotic/mixed culture of Lactobacillus
bulgaricus and Streptococcus thermophilus, curd
contains a mixture various strains of LAB or yeast or
combination of both. Thus the quality of dahi may vary
with the type of starter culture used. Otherwise the
mode of preparation is almost similar to yoghurt. Poor
quality milk, unhygienic practices associated with the
preparation and the use of wild type of starter culture
give rise to poor grade dahi having less shelf-life. They
may not have the probiotic potentials and may not be
as good as yoghurt.
2.1. Probiotics
Probiotics can be bacteria, moulds or yeast. But most
probiotics are lactic acid bacteria consist of a number
of heterogenous bacterial genera within the phylum
Firmicutes. The genera Carnobacterium,
Enterococcus,
Lactobacillus,
Lactococcus,
Lactosphaera, Leuconostoc, Melissococcus,
Oenococcus,
Pediococcus,
Streptococcus,
Tetragenococcus, Vagococcus and Weissella are
recognized as LAB. Depending on the organism,
metabolic pathways differ when glucose is the main
carbon source: homofermentative bacteria such as
Lactococcus and Streptococcus yield two lactates
from
one
glucose
molecule
(Embden-Meyerhof-Parnas pathway), whereas the
heterofermentative (ie. Leuconostoc and Weissella)
transform a glucose molecule into lactate, ethanol and
carbon dioxide (pentose phosphate pathway)
(Sonomoto and Yokota, 2011). In addition, LAB
produces small organic compounds that give the
aroma and flavor to the fermented product. All
probiotic bacteria are LAB but all LAB are not probiotic.
We observed also the same phenomenon in our study
(Shruthy et al., 2011). LAB has been cited to be part
of human and animal microbiota. LAB constitutes an
integral part of the healthy gastrointestinal (GI)
microecology and is involved in the host metabolism.
LAB and gut microbiota ferment various substrates like
lactose, biogenic amines (Stadnik and Dolatowski,
2012) and allergenic compounds and convert into
short chain fatty acids (SCFA), organic acids, gases
and also synthesise enzymes, vitamins (Rossi et al.,
2011), antioxidants (Gowri and Ghosh, 2011;
Achuthan et al., 2012) and bacteriocins (Lasta et al.,
2012). With these properties, intestinal LAB
constitutes an important mechanism for the
metabolism and detoxification of foreign substances
entering the body. Table 1 shows the use of several
microorganisms with probiotic potentials.
Table 1
Commonly used microorganisms as probiotics
See Illustration 1
2.1.1. Characterisation of lactic acid bacteria
Phenotypic characterisation includes identification of
colony morphology, gram staining, fermentation
patterns or a combination of these methods. With the
developing technology, molecular typing is getting
more reliable to identify and differentiate bacterial
strains. Many of these techniques are based on the
polymerase chain reaction (PCR) using
oligonucleotide primers to amplify targeted DNA
fragments, to different taxonomical levels, from
genus-specific differentiation, to the species-specific
level, to sub-species level and also further to the
strain-level. In a separate study, we isolated probiotic
LAB from fermented non-milk food and characterized
both phenotypically and genotypically and identified
using 16S rDNA where we reported a strain,
Pediococcus sp. (GS4), Pom4 (Gowri and Ghosh,
2010a). In addition, PCR based Pulse-Field Gel
Electrophoresis (PFGE) (De Baets et al., 2009; Strus
et al., 2012) techniques, Denaturing gradient gel
electrophoresis (DGGE) (Dalmacio et al., 2011)and
temperature gradient gel electrophoresis (TGGE)(
McCartney, 2002)analysis of faecal 16S rDNA (Gowri
and Ghosh, 2010; Kumaret al, 2012) gene and its
rRNA amplicons have shown to be powerful
approaches in determining and monitoring the
probiotic community.
2.1.2. Selection criteria for probiotics
There is considerable interest in probiotics for a variety
of medical conditions, and millions of people around
the world consume probiotics daily for perceived
health benefits. The probiotic must be able to survive
extremely harsh condition found in the digestive tract
of the host. This involves the ability to survive the high
acidity of the stomach as well as the concentrated bile
found in the small proximal of the intestine. It should
persist, albeit for short periods in the gastro-intestinal
tract influencing metabolic activities like cholesterol
assimilation, lactase activity and vitamin production.
They need to avoid the effects of peristalsis, which
tend to flush out bacteria with food. The survival of
probiotic organisms in the gut depends on the
colonization factors they possess, organelles which
enable them to resist the antibacterial mechanisms
that operate in the gut. In addition to these biological
criteria, probiotic intended for human use must also be
commercially feasible and technologically compatible
with the food manufacturing process. Thus they must
be mass producible, remain viable on storage and
maintain the characteristic sensory attributes of the
traditional food. General biological criteria for
probiotics include: acid tolerance; bile salt tolerance;
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adherence to the gut mucosa; ?-galactosidase activity;

antibiotic resistance; and antimicrobial potential.
2.1.2.1. Acid tolerance
Bacteria used as probiotic adjuncts are commonly
delivered in a food system and therefore begin their
journey to the lower intestinal tract via mouth. It was
reported that the duration of acidic stress from
entrance to release from the stomach to be 90min
which can cause cellular damage at Low pH of 1.5.
However, many of the Lactobacilli isolated from the
ileal samples performed well and could successfully
transit the stomach and capable of reaching the
intestinal environment and function effectively. The
mechanism involved in acid tolerance is not known,
however studies in mice models have inferred that
genes induced upon exposure to acid was identified to
play a role in survival of Lactobacillus strain under
acidic conditions.
2.1.2.2. Bile tolerance
Bile acids are synthesised in the liver from cholesterol
and are secreted from the gall bladder into the
duodenum in the conjugated form (500700 mL/d).
Microbial activity in the colon brings about extensive
chemical
modifications
(deconjugation,
dehydroxylation,
dehydrogenation,
and
deglucuronidation) to the secreted bile acids (He et al.,
2012). In vitro studies have shown that both
conjugated and deconjugated bile acids exhibit
antibacterial activity. Several studies have shown the
involvement of gene activation due to membrane
stress or oxidative damage upon exposure to bile
acids. Research has shown that the permeability of L.
acidophilus cells was increased in the presence of bile.
Increased permeability allows more substrate to enter
cells so that the ?-galactosidase activity of the whole
cell is increased.
2.1.2.3. Adhesion to the gut mucosa
Attachment is considered as a necessary first step in
the colonisation of the host mucosal surfaces. HT-29
and Caco-2 cells are human intestinal cell lines
expressing morphologic and physiologic
characteristics of normal human enterocytes that have
been exploited to elucidate the mechanisms mediating
adhesion. And it explains that mechanism of adhesion
is not unique for all Lactobacilli. Most Lactobacilli have
been shown to adhere via binding to collagen type I
and a few strains to other proteins such as fibronectin,
fibrinogen and lactoferrin.
2.1.2.4. ?-galactosidase activity
?-Galactosidase reduces lactose intolerance and is an
important therapeutic property of probiotic bacteria.
The prevalence of lactose intolerance varies

depending on ethnic origin and is caused by the
deficiency in ? Galactosidase, resulting in the inability
to digest the disaccharide lactose. On reaching the
large bowel, the undigested lactose is degraded by
bacterial enzymes, leading to osmotic diarrhoea.
Lactose intolerant individuals develop diarrhoea,
flatulence and abdominal pain after consumption of
milk. LAB with probiotic potential contain the ?
Galactosidase enzyme which aids in lactose digestion
in the small intestine after being released from
bacterial cells upon exposure to bile acids (Zrate and
Chaia, 2011).
2.1.2.5. Antibiotic resistance
One of the most important safety aspects of LAB is
their resistance to antimicrobial drugs that might be
transferred to other possible, pathogenic bacteria.
Moreover, the resistance profile of LAB to antibiotics
will enable to clarify their potential in minimizing the
negative effects of antibiotic therapy on the host
bacterial ecosystem. The Lactobacillus species have
been found susceptible to many cell wall synthesis
inhibitors like penicillin and ampicillin, however
resistance to vancomycin has been demonstrated
being intrinsic.
2.1.2.6. Antimicrobial potential
Probiotics have the ability to produce antimicrobial
compounds against pathogenic and carcinogenic
bacteria and also to adhere to and colonise the
intestinal gut mucosa. LAB is known to produce
bioactive molecules such as organic acids (Lactic,
acetic and propionic acid), Carbon dioxide, H2O2, low
molecular weight substances as well as protein-like
antimicrobials called Bacteriocins (Gomes et al.,
2012). Inhibition of the growth of pathogenic bacteria
because of antimicrobials is biologically significant as
it is thought to be that of amensalism, a means of one
bacterium gaining advantage over another competing
bacterium. In our study, several of our probiotic isolate
have shown to produce bacteriocin like Pediocin from
Pediococcus spp. GS4 with molecular weight of 9.9
kDa that inhibits the growth of Staphylococcus aureus
(ATCC 25923), Listeria monocytogens (ATCC 15313)
and diarrhoeagenic bacteria including Shigella
dysenteriae type1, S. sonnei, Salmonella typhimurium,
Vibrio cholerae O1 and O139 (Gowri and Ghosh,
2010; Gowri and Ghosh, 2010a; Shruthy et al., 2011).
2.1.2.7. Organic acids
LAB is characterised by the accumulation of organic
acids and the accompanying reduction in pH. It has
been proposed that the low external pH causes
acidification of the cell cytoplasm, while the
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undissociated acid, being lipophilic, can diffuse

passively across the membrane (Schellenberg et al.,
2012). The undissociated acid acts by collapsing the
electrochemical proton gradient, or by altering the cell
membrane permeability which results in disruption of
substrate transport systems. One among the organic
acids is the lactic acid, a major metabolite of LAB
fermentation. It is in equilibrium with its undissociated
and dissociated forms, and the extent of the
dissociation depends on pH. Different microorganisms
vary considerably in their sensitivity to lactic acid.
Heterofermentative LAB strains are known to produce
acetic and propionic acids in addition to lactic acid
through metabolic pathways. These acids interact with
the cell membrane and cause intracellular acidification
and protein denaturation.
Diacetyl is produced by strains within all genera of

LAB by citrate fermentation (Gallardo-Escamilla et al.,
2005). The antimicrobial effect of diacetyl has been
known since the 1930s. It inhibits the growth of
Gram-negative bacteria by reacting with the
arginine-binding protein, thus affecting the arginine
utilisation. Acetaldehyde is another aroma compound
produced by L. delbrueckii subspecies bulgaricus by
the action of a threonine aldolase, which cleaves
threonine into acetaldehyde and glycine. It can
accumulate in the product at a concentration of about
25 ppm. It was shown experimentally that
Staphylococcus aureus, Salmonella typhimurium and
E. coli in dairy products are completely inhibited by
acetaldehyde at a concentration of 10-100 ppm.
2.1.2.8. Hydrogen peroxide
Some Lactobacilli and Lactococci possessing lipolytic

activities produce significant amounts of fatty acids
with antimicrobial potential under specific conditions.
The unsaturated fatty acids are active against
Gram-positive bacteria, and the antifungal activity of
fatty acids is dependent on chain length, concentration,
and pH of the medium. Reuterin is produced during
the anaerobic growth of Lb. reuteri by the action of
glycerol dehydratase, a heterofermentative species
inhabiting the gastrointestinal tract of humans and
animals which has been chemically identified to be
3-hydroxypropanal (?-hydroxypropionaldehyde), a
highly soluble pH-neutral compound which is in
equilibrium with its hydrated monomeric and cyclic
dimeric forms. Reuterin exhibits a broad spectrum of
antimicrobial activity against certain pathogenic
Gram-positive and Gram-negative bacteria, yeast,
fungi and protozoa (Schaefer et al., 2010).
H 2 O 2 is produced as a result of the action of

flavoprotein oxidases or nicotinamide adenine
dihydroxy nucleotide (NADH) peroxidase in the
presence of oxygen. It has been reported that the
production of H2O2 by Lactobacillus and Lactococcus
strains inhibited Staphylococcus aureus,
Pseudomonas spp. and various psychotrophic
microorganisms in foods. The antimicrobial activity of
H 2 O 2 may result from the oxidation of sulphydryl
groups thereby causing denaturation of a number of
enzymes, as well as the increased membrane
permeability as a result of peroxidation of membrane
lipids (Schellenberg et al., 2012). This may cause DNA
damage through the production of bactericidal free
radicals such as superoxide (O2-) and hydroxyl (OH.)
radicals with H2O2 serving as a precursor for the free
radical cascade. In raw milk, H 2 O 2 activates the
lactoperoxidase system, producing hypothiocyanate
(OSCN-), higher oxyacids (O2SCN- and O3SCN-) and
intermediate oxidation products that are inhibitory to a
wide spectrum of Gram-positive and Gram-negative
bacteria.
2.1.2.9. Carbon dioxide
Carbondioxide is also one of the end products of
heterofermentative metabolism. CO2 has effectively
inhibited the growth of many food spoilage
microorganisms,
especially
Gram-negative
psychrotrophic bacteria. With CO2 at 10% lowering the
total bacterial counts by 50% and at 20-50% exhibited
strong antifungal activity. CO2 could play a role in
creating an anaerobic environment which inhibits
enzymatic decarboxylation reaction and the
accumulation of CO2 in the membrane lipid bilayer
may cause a malfunction in permeability.
2.1.2.10. Aroma compounds
2.1.2.11. Fatty acids
2.1.3. Bacteriocins as antimicrobials

Some LAB strains ribosomally synthesise antimicrobial
peptides, or bacteriocins, targeted to inhibit other
Gram-positive bacteria (Gomes et al., 2012).
Bacteriocins permeate the outer membrane of
Gram-negative bacteria and induced the inactivation in
conjunction with other enhancing antimicrobial
environmental factors, such as low temperature,
organic acid and detergents. Bacteriocins produced by
LAB are classified into three main groups, lantibiotics
being the most documented and industrially exploited.
The groups are lantibiotics (Class I), non lantibiotics,
small heat-stable peptides (Class II) and large
heat-labile protein (Class III) The lantibiotic nisin
naturally produced by Lactococcus lactis ssp. lactis is
commercially available as food additive E234. Besides
the production of bacteriocins, some LAB is able to
synthesise other antimicrobial peptides including
low-molecular-mass metabolites, and/or cyclic
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dipeptides.
2.1.4. Role of probiotics in human health
Attempt has been made to unify the hypothesis for
health benefits achieved using probiotics (Heineman
et al., 2012). Several results include lowering the
frequency and duration of antibiotics-associated
clostridial diarrhea, rotaviral infection, chemotherapy
and Travellers diarrhea; stimulation of immunity and
decrease in unfavourable metabolites like ammonia
and procarcinogenic enzymes in the colon. Some
more benefits have been experienced over the recent
times which specify the i) reduction of Helicobacter
pylori infection (Baryshnikova, 2012), ii) reduction of
allergic symptoms (Matsuda et al., 2012), iii) relief
from constipation (Liu, 2011; Malaguarnera et al.,
2012), iv) relief from irritable bowel syndrome
(Thomson et al., 2012), v) beneficial effects on mineral
metabolism (Lamberti et al., 2011; Rossi et al., 2011),
vi) cancer prevention (Escamilla et al.,2012; Maroof et
al., 2012), and vii) reduction of cholesterol and
triacylglycerol plasma concentrations (Wang et al.,
2012).
The role of probiotic organisms as alternative or
complementary therapy in combating a large number
of disorders, especially gastrointestinal and their ability
to enhance immune response has attracted global
attention. A brief outline has been drawn here to
introduce the some health benefits of probiotics.
2.1.4.1. Lactose intolerance
Most of the worlds population (60-90% of
non-caucasians and 6-12% of Caucasians) become
lactose intolerant after weaning, this stems from a
90-95% decline in the production of lactase. The
presence of lactose alters the osmotic balance in the
colonic lumen and develops symptoms including
abdominal bloating, cramping, flatulence and diarrhea.
The contribution of lactase by the bacterial cultures
used to manufacture the probiotic curd (yoghurt) is
thought to mediate enhanced lactose digestion. In
general, results have indicated that probiotics
effectively improve the digestion of lactose and this
effect seems to be more cell-density dependent than
strain specific.
2.1.4.2. Cholesterol reduction
The WHO has predicted recently that by 2030,
cardiovascular diseases will remain leading causes of
death, affecting approximately 23.6 million people
around the World. The risk of heart attack is three
times higher in those with hypercholesterolemia,
compared to those who have normal blood lipid
profiles. The cholesterol-lowering activity of certain
fermented milk and dairy products with some species
of Lactobacillus, Bifidobacterium, Enterococcus, and

Streptococcus has been demonstrated in rats,
hamsters, and pigs. A human strain with similar
cholesterol assimilating properties has been
discovered. L. acidophilus designated strain NCFM
had an appreciable ability to assimilate cholesterol.
The in vitro studies have evaluated a number of
mechanisms proposed for the cholesterol-lowering
effects of probiotics and prebiotics. One of the
mechanisms includes enzymatic deconjugation of bile
acids by bile-salt hydrolase of probiotics. Once
deconjugated, bile acids are less soluble and
absorbed by the intestines, converted to coprostanol,
leading to their elimination in the faeces.
2.1.4.3. Irritable bowel syndrome
Irritable Bowel Syndrome (IBS) is the most common
functional gastrointestinal disorder with a reported
prevalence in the general population between
12%22%. IBS is characterised by a collection of
functional gastrointestinal symptoms such as
abdominal pain, defecatory frequency and/or
constipation. The etiology of IBS is still not clear and
numerous factors are involved in the damage to the
mucosa, including microorganisms, psychological
factors and nutritional habits. In addition, the
gut-associated immune system is up regulated as
evidenced by increased inflammatory cytokines such
as interleukin 1, 6, and 10. The upregulated
gastrointestinal (GI) associated immune tissue is
known to stimulate discharge of enterochromaffin cells
and other cells, which release serotonin and/or
histamine resulting in GI symptoms. The type of
colonising microflora may play an important role in
regulating immunity. IBS patients host an intestinal
microflora containing few Lactobacilli and a decrease
in Bifidobacteria faecal concentration. In normal
conditions, an immunologic tolerance is maintained
toward the commensal enteric bacteria which prevent
intestinal inflammation. This controlled homeostatic
response is lost in susceptible individuals that develop
chronic aggressive cellular immune response at the
intestinal level. Oral administration of L. rhamnosus
GG (LGG) in patients with Crohns disease resulted in
the promotion of the intestinal IgA immune response,
reduction in the pain and severity scores in patients.
Positive role of probiotics in IBS are convincing but a
trend to the beneficial effect of bacterial
supplementation as an adjunct to treatment is
emerging.
2.1.4.4. Colon cancer
Colorectal cancer is one of the leading causes of
cancer morbidity and mortality in many countries and it
is thought to be caused by an interaction between
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dietary factors and genetic predisposition. Diet is

estimated to be responsible for 30 to 60 percent of all
cancers. Genotoxic carcinogens including heterocyclic
aromatic amines, which are formed during the cooking
of meat, increase the potential risk factor of colon
cancer in high-meat consumers. Epidemiological
studies have shown that consumption of fermented
milk products, especially those containing probiotic
bacteria, may help reduce the risk of cancer at a
number of sites. Lactobacillus acidophilus,
Lactobacillus casei Shirota strain and LGG have been
shown to have inhibitory properties on chemically
induced tumours in animals. There is some evidence
that probiotics can interfere at various stages of the
cancer process, such as prevention of DNA damage in
the colon by live bacteria, suppression of
pre-neoplastic changes in the colon and suppression
of colon tumours in animals. Preliminary studies on the
effect of probiotic consumption on cancer appear to be
promising. However further studies are needed before
the beneficial effects of probiotics in the prevention of
human colon cancer can be confirmed.
2.1.4.5. Probiotics and dental health
Probiotics may be beneficial for the oral microflora by
preventing the growth of harmful bacteria such as
Streptococcus mutans. A few studies are available on
the dental effects of LAB and fermented products.
Russian Scientists have reported that probiotic
Bifidobacteriuim spp. can reduce gingival and
periodontal inflammation. Lactobacillus GG (ATCC
53103) has been studied for the colonising properties
in the oral cavity. In healthy volunteers, it was
observed to colonise oral mucosa for up to two weeks
after completion of the oral intake. Some of the
hypothetical mechanisms of probiotics action in the
oral cavity include binding of oral micro-organisms to
proteins, action on plaque formation and on its
complex ecosystem by competing and intervening with
bacterial attachments and involvement in metabolism
of substrate, production of chemicals that inhibit oral
bacteria like antioxidants (Gowri and Ghosh, 2011).
2.1.5.
Features of probiotics to develop a
functional product
An effective probiotic is required to function under
various environmental conditions and has to survive in
many different forms. The candidate probiotic should
possess some characteristics:
1. Acid tolerance and tolerance to human gastric juice.
2. Bile tolerance (an important property for survival in
the small intestine)
3. Adherence to epithelial surfaces and persistence in
human GI tract.
4. Immuno-stimulation,
5. Antagonistic activity against pathogens such as,
Helicobacter pylori, Salmonella typhimurium, Listeria
monocytogens and Clostridium difficle.
6. Antimutagenic and anticarcinogenic properties.
7. Should maintain viability and activity in the carrier
food for long periods under storage and field
conditions (industrial scale) before consumption.
2.2. Prebiotics
Prebiotic is a non-digestable food ingredient that
confers benefits on the host by selectively stimulating
the growth and/or the activity of one bacterium or a
group of bacteria in the colon and thus improves host
health (Gibson and Roberfroid, 1995; Ooi and Liong,
2010; Gourineni et al., 2011; Salvini et al., 2011; Yeo
et al., 2009) and promotes the growth of certain
probiotics. Thus, the prebiotic approach advocates the
administration of non-viable entities. Dietary
carbohydrates, such as fibres, are candidate prebiotics,
but most promise has been realized with
non-digestible oligosaccharides, because of their
selective metabolism. As prebiotics exploit non-viable
food ingredients, their applicability in diets is wide
ranging. Prebiotics could also be termed as Colonic
foods, i.e., food that enter the large intestine (colon)
and which serve as substrates for endogenous and
autochthonous colonic bacteria, thereby indirectly
providing the host with energy, metabolic substrates
and essential nutrients. Resistant starch and
non-starch polysaccharides (NPS) are classified as
colonic foods but not as Prebiotics, as they are not
metabolized by a limited number of beneficial bacteria.
However, some non-digestible oligo-saccharides are
classified as both colonic foods as well as Prebiotics.
Fructo-oligosaccharides (FOS), transgalactosylated
disaccharides (TOS/GOS) and soybean
oligosaccharides (SO) are the only products
recognized widely and are used as food ingredients
that meet all the requisites of probiotic classification.
Besides these, xylo-oligosaccharides (XOS), lactulose
and lactitol are also considered as Prebiotics. The
prebiotic activity of FOS has been confirmed in both
laboratory and human trials. This is because these
carbohydrates have a specific colonic fermentation
directed towards bifidobacteria. Bifidobacteria are able
to break down and utilize fructo-oligosaccharides due
to their possession of a ?-fructofuranosidase enzyme,
providing a competitive advantage in a mixed culture
environment like the human gut. XOS are used as
food ingredients owing to their technological properties
and healthy effects. Xylobiose (X2) (degree of
polymerization; DP=2) is considered a member of
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XOS with beneficial effect in GI tract. Results obtained

in vivo using rats proved the administration of XOS
resulted in increased amounts of Bifidobacterium spp.
with the increase of SCFA. It has been observed that
ingested X2 is not excreted in feces or in urine in the
24h following oral administration. Since X2 cannot be
hydrolysed either by saliva, pancreatin, gastric juice,
or intestinal mucosa homogenate, suggest X2 is
utilized by intestinal microflora. GOS are another class
of prebiotics that are manufactured and marketed in
Europe and Japan. These consist of a lactose core
with one or more galactosyl residues linked via ?1?3,
?1?4 and ?1?6 linkages. They have found application
in infant formula foods. Table 2 shows the
classification and sources of Prebiotics.
Table 2
Classification and sources of Prebiotics
See Illustration 2
Prebiotics are with following characteristics: i) they are
parts of edible plants; ii) they are carbohydrates that
are composed of mixture of oligosaccharides/ and
polysaccharides (degree of polymerization differs); iii)
resist hydrolysis by human digestive enzymes; iv) do
not appear to be significantly absorbed in the small
intestine (exception remains with very short chain
oligosaccharides); v) they are not metabolized by the
host; and vi) they are excreted as such in the urine.
However, the dietary intake of OS is difficult to
estimate, but it may reach 3-13 g/day per person.
Certain studies indicate that daily intake of 5-20 g of
Inulin and FOS selectively promotes the growth of
Bifidobacteria. Such studies are not available in India.
A large number of beautiful and excellent review
articles are available to gain interesting information
about pro- and pre-biotics. However, the common
understanding about the utility of Prebiotics is that they
benefit our intestinal ecosystem, improve immunity
and overall health. Probiotics along with Prebiotics
have been significantly used for the clinical benefit in
the prevention and management of gastrointestinal
and non-gastrointestinal conditions(Sazawal et al.,
2010; O Donnell et al., 2011) like necrotizing
enterocolitis, Travellers diarrhea, allergic colitis,
inflammatory bowel diseases and in pediatrics
gastrointestinal disorders, by increasing biomass of
probiotics and stool bulking.
2.3. Synbiotics
A further approach is synbiotics, where probiotics and
prebiotics are combined. Synbiotics are preparations
that contain probiotics as well as prebiotics. Synbiotics
further improve the efficacy of the probiotic and
prebiotic when used individually. This occurs because
the prebiotic boosts the growth of the surviving

probiotic once it reaches the area of the intestine
where it would multiply. The symbiotic concept
combines efficacious probiotic strains with specific
probiotic compounds in a single product (Zhang et al.,
2010; Fotiadis et al., 2008; Bengmark, 2012; Martin et
al., 2012). Synbiotic is defined as a mixture of
probiotics and prebiotics that beneficially affects the
host by improving the survival and implementation of
live microbial dietary supplement in the GI tract.
Synbiotics are mostly prepared by adding prebiotic
ingredients / dietary fibre or value added ingredients
along with probiotics having some intention of health
advantage. More than 350 products have been
approved under Food for specific health use (FOSHU)
as on 1st April,2011 with a claim to control GI functions
(helps to maintain good GI condition and to improve
bowel movement), which include oligosaccharides,
Lactobacillus, Bifidobacteria, dietary fibres/
non-digestible oligosaccharides. Several synbiotic
formulations have been reported in literature. Among
all, preparation with cassava starch or inulin, milk and
three different LAB; lactulose, inulin with L. acidophilus
LA-5 and B. bifidum BB-12; inulin, FOS and honey
with L. acidophilus; sugar with inulin and probiotcs;
raftiline, raftilose with honey, milk and LAB are worth
mentioning. In our study, we prepared several
formulations (capsule) for delivery of probiotics (our
strains Pediococcus sp.GS4, L. lactis and L. gasseri)
for health benefits. Our preparations contain several
different Prebiotics as excipients which include XOS,
FOS, inulin, skim milk, dulcitol, xylitol, lactitol, honey,
ascorbic acid in permutation and combination. It is
also reported that Prebiotics products are available in
the form of tablet or powder and mint wafers, which
contains inulin and calcium (500 mg), manufactured by
the company, Naturally Vitamines under brand name
of InufloraTM and Inu-Lean respectively. Stonyfield
Company, sells synbiotic products in blended
flavoured yoghurt form containing six live active
culture and inulin. A large number of scientific
literatures are there to claim its use in different clinical
gastrointestinal (GI) conditions as displayed in Table
3.
Table 3
Clinical applications of Synbiotics in several GI
conditions
See Illustration 3
3.
Mechanisms of action of synbiotics on
mucosal surface of GIT
Gastrointestinal tract (GIT) represents a complex
ecosystem in which a delicate balance exists between
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the intestinal microflora and host. It comprised of 95%

obligate anaerobes including Bifidobacterium,
Clostridium,
Eubacterium,
Fusobacterium,
Peptococcus, Peptostreptococcus, Bacteriodes and
others. About 1-10% of intestinal population is
composed of facultative anaerobes including
Lactobacillus, Escherichia coli, Klebsiella,
Streptococcus,
Staphylococcus.
Aerobic
microorganisms are not present in the GIT. The
distribution of these hosekeeping bacteria differ from
oral cavity to anus. The load of microbiota vary from
102- 1012 colony forming unit (cfu) per gram of aspirate
or stool and vary also with age, gastric acid secretion,
diet, life style and time feeding. In general, we the
Homo sapiens sapiens possess 10 times more
microbiota than our cells content (1013). In the small
intestine, jejunum and ileum contain no more than 104
-105, whereas the terminal ileal content increases by
10-100 folds. On opening into the gut, the microbial
load increases by million fold and reaches to 1011 to1012
cfu/gram of stool. Each individual has a rather unique
colonic flora that remains constant over long periods of
time, with minor variations conditioned by frequency of
bowel movement and diet. Uniquely, the morphology
of gut is governed by the microbiota and maintains the
homeostasis of the host (Marik, 2012).
The therapeutic applications with probiotics, prebiotics,
and synbiotics are moving fast in the recent decade.
The effectiveness of probiotics is strain-specific, and
each strain may contribute to host health through
different mechanisms. Many reports indicate that
probiotics can affect innate immunity and also protect
against pathogens by decreasing pathogenic
adherence or by production of acids, H 2 O 2 ,
bacteriocins or several surface active molecules which
are inhibitory to pathogens in gastro-intestinal tract.
Probiotics have been found to control intestinal
disorders, partially due to immunomodulating the
innate pattern-recognition receptors such as TLRs,
NLRs and CLRs and because of serum antibodies IgG,
and secretory IgA and IgM enhancing immune
response. Certain strains can intermittently translocate
across the intestinal mucosa without causing infection,
thus influencing systemic immune events. Evidence
has been presented that some Lactobacilli can directly
stimulate the immune system on the gut mucosal
surface via localised GI tract lymphoid cell foci. In a
recent study, potential of twenty seven lactobacilli and
sixteen bifidobacteria strains were compared to
stimulate bone-marrow derived dendritic cells. Most of
them induced strong production of IL-12 and TNF-?
(DSouza et al., 2012).
A number of mechanisms work to prevent harmful
bacteria from growing on and attaching to the

intestinal epithelium: production and secretion of
antimicrobial agents such as bacteriocins and organic
acids, adherence via competition for the binding sites
and steric hindrance and barriers interfering with
pathogens and hence promote the elimination of
harmful bacteria. The probiotic exert multiple potential
to confer health benefit to the host following several
mechanisms which 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, like exopolysaccharides 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. A summary has been
drawn to demonstrate the possible mechanisms of
actions offered by probiotics-prebiotics or synbiotics to
enhance the health benefit to humans with special
reference to GI conditions as in Table 4.
Table 4
Summary of mechanisms of action of probiotics
and the impact on health including GI Tract.
See Illustration 4
4. Mechanisms of beneficial effects

The origin of cultured dairy products dates back to the
dawn of civilization and mention of them is found in the
Bible and the sacred books of Hinduism. However, the
association between these products and human health
was not realized until 1900s. During the same period
of Metchnikoff, Cohendy observed that human
subjects administered with sour milk containg L.
bulgaricus were with reduced putrefaction, while Henry
Tissier observed that children with diarrhea had in
their stools a low number of Bifidobacteria, on the
contrary, abundant in healthy children and suggested
that these bacteria could be administered to patients
with diarrhea to help restore a healthy gut flora in 1906.
In the early 1920s, Rettger and Cheplin (1922)
documented that L. acidophilus milk had therapeutic
effects, in particular, a settling effect on digestion.
They believed that colonisation and growth in the gut
were essential for efficacy, and therefore, advocated
the use of intestinal isolates. This kindled further
interest in understanding the survival and colonisation
of Lactobacillus spp. Since then yoghurts were in
common use and were found efficacious in
maintaining the balance of the gut flora or to prevent
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conditions, such as, diarrhoea, constipation, dyspepsia,

cystitis, mucous colitis, chronic ulcerative colitis and
dermatitis. Shirota focused his research on selecting
strains of intestinal bacteria that could survive passage
through the gut and on the use of such strains L.
acidophilus Shirota (subsequently named L. casei
Shirota) ( Dong et al., 2010; Hori et al., 2002) was the
basis for the establishment of the Yakult Company.
Gordon and colleagues noted that the success of
therapy using Lactobacillus was depended on certain
criteria: it was essential to use a non-pathogenic
organism which is a normal inhabitant of the intestine
and capable of establishing itself in the gut and that a
large number of viable cells (107-109) were essential
for the establishment of a beneficial flora. The
co-administration of a diet with high milk or lactose
content or the growth factors required by Lactobacilli
was also considered as a key factor for successful
bacterial therapy. The scientific basis of probiotics and
the health benefits related to the consumption of food
containing viable LAB has branched from this history
and opened many new avenues for exploiting optimal
benefits from these microbes. The probiotics has the
best potential to be the best therapeutics for all sorts
of diseases and disorders, the Panacea in near future
( Martin et al., 2012).
Lactobacillus and Bifidobacterium species originating
from human microflora have been a matter of interest.
Hence Probiotics are sometimes called colonic foods.
Lactobacilli have a long history of safe use in foods
and dairy products. Lactobacilli are normal inhabitants
of the intestinal ecosystem and vagina but variable
amounts are found among people (ranging from 0 to
10 6 cfu/g faeces). The therapeutic roles of some
Lactobacillus spp. have been demonstrated.
Lactobacillus rhamnosus GG (LGG) was the first
probiotic which received most clinical attention to date
(Vandenplas et al., 2007). The Lactobacillus strain
used traditionally for fermentation by the dairy industry
was unable to implant to the gut so, LGG was
discovered in 1985 by developing a list of ideal
qualities for probiotics, as mentioned earlier. LGG has
proven beneficial effects on the intestinal immunity. It
increases the number of IgA and other
immunoglobulin secreting cell in the intestinal mucosa,
stimulates the local release of interferons, facilitates
antigen transport to underlying lymphoid cells which
severs to increase antigen uptake in the Peyers
patches.
Bifidobacteria are also part of the human and animal
microflora, but species differ according to age:
newborns are readily colonised by Bifidobacterium
breve and B. infantis and colonisation is favored in
breast-fed compared to bottle-fed infants, whereas

adults more often host B. adolescentis, B. bifidum and
B. longum. Presently there are about 30 species
included in the genus Bifidobacterium, 10 of which are
from human sources and 17 from intestinal tracts of
animal or rumen. Of these, six species from human
origin, B. adolescentis, B. breve, B. bifidum, B. lactis,
B. infantis and B. longum have been used in dairy
products. It has now been conclusively demonstrated
that some Bifidobacterium strains can survive
intestinal transit and persist transiently within the colon.
The therapeutic roles of Bifidobacteria in animal model
and in human are due to four major mechanisms
including modulation of the host immune system,
resistance to infectious diseases such as against
rotavirus diarrhoea and enteropathogens , control of
inflammatory bowel disease such as Crohns disease,
ulcerative colitis and pouchitis and prevention of
cancer. Persistance of ingested Bifidobacterium in the
digestive tract is dependent on the contribution of host
genotype to the dominant microbial diversity
suggesting specific interactions between microbes and
humans. On the other hand, microflora establishment
and maintenance is highly dependent on the food
intake and style of diet. Among the other probiotics,
Enterococcus faecium SF68 strain has been used in
the management of diarrhoeal illnesses.
Non-pathogenic probiotic yeast, Saccharomyces
boulardii has also shown beneficial effect in the
treatment of diarrhea associated with antibiotic use.
5. Clinical studies of probiotics in diarrheal
disease and other GI infections
In India, about 59% of prescriptions for the treatment
of diarrhoea were fixed dose combinations of an
antibacterial and an antiprotozoal. Such combination
has risks of adverse drug reactions and also increases
the chances of drug resistance. Physicians in India are
influenced by socio economic factors and so a cheap
way for the management of diarrhoea is necessary
(Reid et al., 2003; Preidis et al., 2011). Probiotics may
be seen as a natural alternative to traditional drugs,
and thus patients may regard probiotics as safer, more
effective, and less likely to pose significant health risks.
Probiotic therapy is preferable to traditional drugs
because it involve a more holistic approach to the
management of disease, are readily available and do
not require the additional costs of a physician visit.
Diarrhoea is the second fatal disease in India and a
common problem of other developing countries. It has
been estimated that there may be 4 billion cases of
acute diarrhoea each year worldwide. All kinds
infectious diarrhea including Cholera, shigellosis and
other infections lead to stunt and slow growth in
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children below five years. Intake of curd has been

found beneficial in a study in India (Saran, 2002). The
balanced normal microbiota may become aberrant on
infection and synbiotics repair the physiological and
immunological processes to maintain the homeostasis.
Diarrhoea is caused by infections, antibiotic therapy,
and tube feeding. Infectious diarrhea is caused by
more than 50 different pathogens including virus,
bacteria, fungus and protozoa and it affects all
age-groups. It is the major cause of high mortality and
morbidity, as seen especially in India. In developing
countries, bacterial enteropathogens, particularly
enterotoxigenic Escherichia coli (ETEC) cause just
under half of the cases of endemic paediatric
diarrhoea and majority of all cases of Travellers
diarrhea (Ghosh et al., 1996). Probiotics have been
best researched as therapeutics for the management
of acute infantile diarrhoea. Rotavirus and
enteropathogenic E. coli (EPEC) are leading cause of
this condition worldwide. At least three systematic
reviews have shown that use of probiotics achieves
overall reductions in the duration of diarrhoea ranging
from 17 to 30 hours. Many mechanisms of action
explaining how lactobacilli reduce the duration of
rotavirus-induced diarrhoea have been proposed (Reid
et al., 2003; Reid et al., 2008; Preidis et al., 2011).
These include competitive blockage of receptor sites
when lactobacilli bind to receptors; signal(s) from
lactobacilli regulating secretory and motility defences
designed to remove perceived noxious substances;
enhancement of the immune response; and production
by lactobacilli of substances that inactivate the viral
particles. However, it is not clear whether the routine
use of probiotics in acute diarrhoeal illnesses is
justified, as most acute diarrhoeal illnesses are self
limited.
There is not much information indicating whether
probiotics reduce the serious complications of
diarrhoeal illnesses (Yan and Polk, 2006).
Furthermore, the data do not provide a clear
understanding of the type, dose, or duration of
probiotic treatment required for achieving clinical
benefit. Limited data suggest that the minimal effective
dose in children is 10 billion colony-forming units given
within the first 48 hours. Another study evaluated the
use of LGG as a prophylactic agent against diarrhoea
in children. The regular administration of a daily dose
of LGG, 6 days a week for 15 months, achieved a low
rate of diarrhoea, but only in nonbreast-fed infants.
Persistent diarrhoea is defined as a diarrhoeal episode
that starts acutely but lasts for 14 days or more, and it
is an important cause of morbidity and mortality in
children under five years old in developing countries
throughout the world. The cause of persistent

diarrhoea is not completely understood but is likely to
be complex; this in turn makes management of the
condition difficult. In a separate study, four clinical
trials involving children with persistent diarrhea were
reviewed in 2010 (Sazawal et al., 2010). Two studies
with a combined total of 324 showed that probiotics
shorten the duration of diarrhoea and reduce the stool
frequency on day 5. One study with 235 hospitalised
children suggested that probiotics reduced the hospital
stay. Three out of four trials reported that no adverse
events occurred. The report was satisfactory but not
overwhelming as every study is limited by few trials
with small number of participants, and therefore may
not represent a reliable estimate of probiotics' effect.
Diarrhoea associated with antibiotic use and caused
by Clostridium difficile is a complication of treatment
with antimicrobial agents and occurs in about 5-25% of
patients. C difficile is responsible for around 15-25% of
all cases of diarrhoea associated with antibiotic use,
most occurring in older patients, usually in the two to
three weeks after cessation of antibiotic treatment.
Lactobacilli, Bifidobacteria, and Streptococcus species
have all been evaluated for the prevention or
treatment of diarrhoea associated with antibiotic use
and found to be safe. In another study conducted in
2007 showed that consumption of a readily available
probiotic drink containing Lactobacillus casei, L
bulgaricus, and Streptococcus thermophilus, twice a
day during a course of antibiotics and for one week
afterwards, reduced the incidence of diarrhoea
associated with antibiotic use and C. difficile.
Two recent hospital-based studies in 2011, reported
reduction in diarrhea duration when S. boulardii was
given to 186 children between 6-48 months, within 72
hours after the onset of acute diarrhea. The result
suggests a complementary treatment of acute diarrhea
in infants with daily oral doses of S. boulardii. In a
separate randomized clinical trial, a total of 111
diarrhoeic children with median age of 40 months were
treated with synbiotics containing S. thermophilus, L.
rhamnosus, L.acidophilus, Bifido lactis with FOS. The
duration of diarrhoeal episodes were one day shorter
than placebo group.
The use of probiotics as prophylaxis against diarrhoea
is an interesting concept that remains unproven
(Culligan et al., 2009; Gratz et al., 2010). The data on
the use of probiotics to manage adults with infective
diarrhoea are limited and mixed. Twenty three
research papers were on the treatment of infectious
diarrhoea with probiotics and concluded that they
appear to be a useful adjunct to rehydration therapy
when managing both adults and children (Allen et al.,
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2004).
laboratories for popularization of this new concept.
6. Products marketed by Indian firms
India has a long tradition in using foods for their

health-promoting or functional properties, influenced
by Ayurvedic medicine. These functional foods can
include herbal extracts, spices, fruits and other
ingredients for fortification and enhanced health
benefit. Increasing health-awarness of synbiotics is
further raising demand for diet foods and fortified
natural foods. Nine out of ten urban Indian consumers
have been reported to generally choose foods based
on health and wellness benefits.
A large number of research results on probiotics,

prebiotics and synbiotics have been translated into
industrial products. Due to its wide-acclaimed
acceptability and simple formulation with dietary utility,
probiotic market has brighter future to safeguard
human lives. The market of functional food or designer
food like synbiotics is governed by several factors
specially the cultural base, geographical location,
demography, economy, level of education in the
society, government interests and others. Properly
formulated probiotic-containing foods having the
potential to promote health benefits offer consumers a
low risk and low cost dietary component. Although the
worldwide market for probiotics or/ and synbiotics is
growing fast and Japan, USA, Europe took the
leadership, however, in India, the market has just
started to conceive with leading companies like Amul,
Nestle, Mother Dairy and Aavin making the first move.
In India, these companies have come up with their
probiotic products, which are very popular. Some of
these are presented in Table 5.
Table 5
Indian company in the Probiotics market
See Illustration 5
Yakult-DANONE India, is the first Indian company with

50:50 joint venture of Japanese global probiotics
leader, Yakult, with the French food major, Group
DANONE, has entered the Indian probiotics market
with launching of their product Yakult, a probiotic curd
in December 2008. At least 39 probiotic drug brands,
mainly in the area of gastroenterology, from 30 major
Indian companies have already created a probiotics
drug market in India worth Rs 80 crore. Major players
in the probiotics drug market in India include
companies like Ranbaxy (Binifit), Dr. Reddy's
Laboratories, which has four probiotic brands, Zydus
Cadila, Unichem, JB Chem, and Glaxo SmithKline.
Many Indian research institutes are working on the
probiotic technologies (Probiotic curd - Punjab
Agricultural University, Ludhiana, Punjab; Probiotic ice
cream - National Dairy Research Institute (NDRI),
Karnal, Haryana; Cereal based probiotic foods
Haryana Agricultural University, Haryana, etc.).
National Research Development Corporation, a Govt.
of India enterprise under Ministry of Science and
Technology, has also taken active role in
commercialization of the probiotic technologies
developed in various Indian research institutes and
Concluding Remarks
The concept of synbiotics is based on the knowledge
of providing therapeutic benefit to human beings
reducing or elimination the risk of gastrointestinal
disorders. Increasing evidences in scientific literature
point out that the consumption of synbiotics
(Bio-yoghurt), particularly containing L. acidophilus
and Bifdobacterium species offers considerable health
benefits through different mechanisms to consumers.
In addition to the nutritional favour there is a need for a
sustained effect to combine the skills of the
microbiology, food technologist and clinician.
Undoubtedly, gut flora can protect the host against
several intestinal diseases. Once the prophylaxis of
probiotics are well established with respect to the
claimed health benefits, probiotics are sure to gain firm
footing in the health food sector of the market and well
certainly be the major portion of functional food sector.
The probiotic dairy foods such as probiotic ice cream,
kulfi, yoghurt drink and dietic yoghurt could be
commercialized through the organized dairy for the
benefit of common people.
The role of probiotic organisms as alternative or
complementary therapy in combating a large number
of disorders, especially gastrointestinal and their ability
to enhance immune response has attracted global
attention. A number of health related effects have
been suggested and partially established but some
can be considered reasonably well established and
clinically well documented. It is hoped that the simplest
formulation will be discovered soon like oral
rehydration solution (ORS) to support the global health
and economy. The potentials with synbiotics ensure to
be a solution to those people where doctors never visit
for the cause of health. It will be very friendly to
ameliorate the public health in near future. The
increase in metabolic activity of probiotics is
fundamental to many of the currently proposed
mechanisms of health promotion by prebiotics.
Synergistic approach in synbiotics will add more
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values to the mitigation, reduction or elimination of

many existing diseases and many more diseases yet
to be enlisted in the era of globalization. Truly,
synbiotics has potentials to be panacea of all earthly
diseases.
Acknowledgements
The Author would like to thank the management of VIT
University, Vellore, India for supporting and performing
the scientific exercise.
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Illustrations
Illustration 1
Commonly used microorganisms as probiotics
Lactobacillus species
Bifidobacterium species
Other bacterial species
B. bifidum
Escherichia coli
L. salivarius
B. longum
Enterococcus faecalis
L. lactis
B. thermophilum
Enterococcus faecium
B. infantis
Leuconostoc spp.
L. gasseri
B. lactis
Pediococcus spp.
L. reuteri
B. animalis
Bacillus spp.
Strptococcus species
S. lactis
VLS#3(Four strains of Lactobacilli, three strains of

Bifidobacterium, one strain of Streptococcus salivarius
spp thermophilus)
S. cremoris
Yeast and Moulds
S. alivarius
Saccharomyces boulardii
S. intermedius
Saccharomyces cerevisiae
S. thermophilus
Aspergillus niger
L. acidophilus
L. rhamnosus
L. paracasei
L. casei
L. fermentum
L. brevis
L. planetarum
L. sporogens
Acanthosis oryzue
Candida pintolopesii
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Illustration 2
Classification and sources of Prebiotics
Classification
Sources
Manufacturing procedure
Sorbitol
Sugar alcohol
Fermentation
Xylitol
Sugar alcohol
Fermentation
Mannitol
Sugar alcohol
Fermentation
Lactulose
Lactose
Synthetic
Lactitol
Lactose
Synthetic
Fructo-oligosaccharides (FOS)
Legumes, vegetables, cereals
Extraction/ hydrolysis
Soybean oligosaccharides (SO)
Soybean
Xylo-oligosaccharides (XOS)
Plant sources
(Trans) Galacto-oligosaccharides (TOS)/ (GOS)
Lactose
Synthetic
Polyols
Disaccharides
Oligosaccharides
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Raffinose
Fermentation
Palatinose
Iso-malto-oligosaccharides
Lactosucrose
Polysaccharides
Inulin
Legumes, vegetables,
cereals
Resistant starches
Legumes, vegetables,
cereals
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Illustration 3
Clinical applications of Synbiotics in several GI conditions
1. Rota virus diarrhea
11. Inflammatory bowel disease
1. Antibiotic-associated diarrhoea
12. Pancreatis
1. Travellers diarrhea
13. Pouchitis
1. Clostridial diarrhea
14. Colon cancer
1. Diarrhiea of various origin
15.Food allergies and lactose intolerance
1. Nosocomial diarrhea
16.Small bowel bacterial outgrowth
1. AIDS diarrhea
17. Dental caries
1. Gastroenterites
18. Cystic fibrosis
1. H. pylori infection
19. Enhancement of oral vaccine
1. Irritable bowel syndrome
20. Liver-gut-brain syndrome
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Illustration 4
Summary of mechanisms of action of probiotics and the impact on health including GI Tract.
Health Benefit
1. Resistance to enteric infections
2. Secretary immune effect
Mechanisms of actions
-Alteration of intestinal conditions to be less
favourable of pathogenicity (pH, short chain
fatty acids, bacteriocins)
-Alteration of toxin binding sites to
enterocytes.
-Influence on gut flora populations.
-Adherence to intestinal mucosa, interfering
with pathogen adherence.
-Upregulation of intestinal mucin
production
-immunomodulation of pro-inflammatory
(IFN, TNF-) and anti-inflammtory
(IL-10) cytokines.
1. Small Bowel decreasing bacterial

infections
-Influence on activity of overgrown flora,

toxic metabolite production
1. Urogenital infctions
-Adhesion to urinary tract and vaginal tract

cells colonization resistance
Page 22 of 27
WMC003796
1. Infection caused by Helicobacter

pylori
-Inhibitor production (H2O2, Lactic acid,

bacteriocins)
1. Promotion of lactose digestion
-production of bacterial lactase to hydrolyse

lactose
1. Immune system modulation
-strengthening of non-specific defense

against infection and tumours by production
of IL-12 and TNF-.
-adjuvant effect in antigen-specific immune
responses
-Enhancement of secretary IgA production
-conjugated leinoleic acid (CLA) of the
probiotics upregulate the PPAR to reduce
inflammation and colon carcinogenesis
1. Hepatic encephalopathy
-Inhibition of urease-producing gut flora
1. Anti-colon cancer effect
-Mutagen binding carcinogen deactivation
1. Inhibition of carcinogen producing

amines and enzymes of colonic
microbes
-Antagonism
Page 23 of 27
WMC003796
1. Effect of alergic states
-Improves immune response

-Influence on secondary bile salt
concentration
-Prevention of antigen translocation into
blood stream
1. Effect on blood lipids and heart

disease
-Assimilation of cholesterol within bacterial

cell
-Increased excretion of bile salts due to
deconjugation by bile salt hydrolase
1. Antihypertensive
-Antioxidative effect
-Peptidase action on milk protein yields
tripeptides which inhibi angiotensin-1
converting enzyme.
-Cell wall components act as ACE
inhibitors
Page 24 of 27
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Illustration 5
Indian company in the Probiotics market
Probiotics Products
Strains used
Company Name
Dairy products
Probiotic curd
Heritage Foods(India)ltd
b-Activ Probiotic Dahi
L.acidophillus and B.lactis strain BB12
Mother Dairy
Nesvita Probiotic yoghurt
L.acidophillus
Nestle (India)
Probiotic Ice-cream Amul Prolife

Yakult
Amul Dairy (India)
L.casei strain shirota
Yakult Danone India Private Ltd.
L.acidophillus, L.rhamnosus,B.bifidus
Alembic
Pharmaceutical products
ACTIGUT
B.longam, S.boulardii,
Fructooligosaccharides
BINIFIT
S.faecalis, C.butyricum, Bacillus

mesentericus, L.sporogenes.
Ranbaxy
BECELAC
L.acidophillus,Vit-B6, Vit-C,Folic acid.
Dr.Reddys Laboratories
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WMC003796
BFILIN
L.acidophillus, L.rhamnosus, B.bifidium, Cipla

B.longum, S.thermophillus,
EQUIPRO
L.acidophillus,S.Faecalis
Cadila Pharma
Clostridiumbutyicum,
Bacillus mesentericus
ECONOVA
L.Reuteri RC-14
Glenmark
L.Rhamnosus GR-1
GUTRITE
L.acidophillus, L.rhamnosus, B.longum,

B.bifidium, S.boulardii, S.thermophillus,
FDC
GUTPROCAPS
S.faecalis
Clostridium butyricum
B.mesentericus,
L.sporogenes
Jb Chem
PROBIZA D
L.sporogenes,
Zydus Cadila
Page 26 of 27
WMC003796
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in 1908, and devoted last decade of his life

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making use of fermented food and beverages using

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role of food as a source of energy to the more subtle

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bacterial culture. Unlike yoghurt which involves the

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adherence to the gut mucosa; ?-galactosidase activity;

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The prevalence of lactose intolerance varies

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undissociated acid, being lipophilic, can diffuse

Diacetyl is produced by strains within all genera of

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Some Lactobacilli and Lactococci possessing lipolytic

H 2 O 2 is produced as a result of the action of

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2.1.2.11. Fatty acids

2.1.3. Bacteriocins as antimicrobials

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of Lactobacillus, Bifidobacterium, Enterococcus, and

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dietary factors and genetic predisposition. Diet is

WebmedCentral > Review articles

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XOS with beneficial effect in GI tract. Results obtained

WebmedCentral > Review articles

the prebiotic boosts the growth of the surviving

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the intestinal microflora and host. It comprised of 95%

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bacteria from growing on and attaching to the

4. Mechanisms of beneficial effects

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conditions, such as, diarrhoea, constipation, dyspepsia,

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breast-fed compared to bottle-fed infants, whereas

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children below five years. Intake of curd has been

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throughout the world. The cause of persistent

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laboratories for popularization of this new concept.

6. Products marketed by Indian firms

India has a long tradition in using foods for their

A large number of research results on probiotics,

Yakult-DANONE India, is the first Indian company with

WebmedCentral > Review articles

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values to the mitigation, reduction or elimination of

WebmedCentral > Review articles