Applications of Probiotics as a Functional Ingredient in Food and Gut Health

Abstract

Probiotics are live microbes which serve as excellent functional food ingredients, to improve human health. They provide essential metabolites with dietary and therapeutic characteristics which confers numerous health benefits. They ensure a proper maintenance of the gut health through complex interactions across the gut-brain axis. The probiotics enter into the body through food. Probiotics can exist naturally or be infused in food. Food products containing probiotics are viable modes for a healthy gut. Understanding the mechanism of action of the probiotic strains and their interaction with the gut microflora is absolutely necessary. This review elaborates on the applications of probiotics in food .It also describes the possible mechanism of action and its clinical significance.

Full text

Journal of Food and Nutrition Research, 2019, Vol. 7, No. 3, 213-223
Available online at http://pubs.sciepub.com/jfnr/7/3/6
Published by Science and Education Publishing
DOI:10.12691/jfnr-7-3-6
Applications of Probiotics as a Functional Ingredient
in Food and Gut Health
Snigdha Misra1,*, Debapriya Mohanty2, Swati Mohapatra3
1Division of Nutrition and Dietetics, School of Health Sciences, International Medical University, 57000, Kuala Lumpur, Malaysia
2Research Associate, Institute of Life Sciences, 751023 Bhubaneswar, Odisha, India
3Department of Biotechnology, Amity University (AIMT), Noida 201313, Uttar Pradesh, India
*Corresponding author: snigdha_misra@imu.edu.my
Received January 13, 2019; Revised February 26, 2019; Accepted March 13, 2019
Abstract Probiotics are live microbes which serve as excellent functional food ingredients, to improve human
health. They provide essential metabolites with dietary and therapeutic characteristics which confers numerous
health benefits. They ensure a proper maintenance of the gut health through complex interactions across the
gut-brain axis. The probiotics enter into the body through food. Probiotics can exist naturally or be infused
in food. Food products containing probiotics are viable modes for a healthy gut. Understanding the mechanism of
action of the probiotic strains and their interaction with the gut microflora is absolutely necessary. This review
elaborates on the applications of probiotics in food .It also describes the possible mechanism of action and its clinical
significance.
Keywords: probiotics, food formulations, gastroenteritis, clinical implications
Cite This Article: Snigdha Misra, Debapriya Mohanty, and Swati Mohapatra, “Applications of Probiotics as
a Functional Ingredient in Food and Gut Health.” Journal of Food and Nutrition Research, vol. 7, no. 3 (2019):
213-223. doi: 10.12691/jfnr-7-3-6.
1. Introduction
Probiotics are a group of health promoting functional
foods with an emerging commercial interest [1]. They are
incorporated as living microorganisms in food to enhance
its nutritional content and protect the gut. Clinically,
probiotics improve the intestinal microbiome contributing
towards the immune potency of the host. They also
counteract the pathogenic activity in the gut. Multiple
mechanisms of actions are reported, including production
of antimicrobial agents, competition for space or nutrients
and immunomodulation [2]. FAO/WHO define probiotics
as “live microbial food supplements or components of
bacteria which when taken up in adequate amounts,
confers a health benefit to the host” [3]. Probiotics have
emerged as medical therapies for gastrointestinal and
non-gastrointestinal diseases such as diarrhea, constipation
inflammatory bowel disease, irritable bowel syndrome,
asthma, atopic dermatitis, peptic ulcer, colon cancer,
coronary heart disease and urinary tract infections
[1].Evidences have supported the consumption of
fermented milk especially yogurt, due to its nutritional
properties in maintenance of gut health, due to its
probiotic content.
This article summarizes the applications of probiotics
as a functional ingredient in food, mechanism of action
and its clinical significance in gut health.
2. Application of Probiotics
in Food Products
The global market of functional foods including probiotics
is growing exponentially. The emerging demand of
consumers is incentivizing world markets to manufacture
dairy and non-dairy products containing probiotic bacteria.
Figure 1 and Table 1 show some dairy and non-dairy
probiotic products available in world markets. Therefore,
putting probiotic bacteria into products is an important
issue with industrial and commercial consequences. This
led to a shift in industries, focusing on the probiotics based
food products, to fulfill consumer demand. Probiotic cells
via food products are available in three different types for
direct or indirect human consumption such as fermented
or non-fermented form, dried or deep-frozen form for
industrial or home uses and drugs in powder, capsule or
tablet forms [4]. Some of the commercially available
probiotic strains are listed in Table 2 [5,6].
2.1. Dairy Based Products
Dairy products serve as a good vehicle for probiotics.
Some examples of dairy based products are; butter milk,
normal milk, flavored liquid milk, fermented milks, dairy
fermented beverage, milk powder, Whey-protein-based
drinks, yogurt drink, ice cream, sour cream, yogurt, cheese,

214 Journal of Food and Nutrition Research
frozen dairy desserts and baby foods are the most popular
vehicles for probiotics [7,8]. Dairy foods are ideal for
performing the delivery function because of their inherent
environment stabilizing properties that promote the
growth of probiotic bacteria, which can then be stored at
refrigerated temperatures. In addition to probiotic strains,
several useful compounds such as tryptone, yeast extracts,
certain amino acids, nucleotide precursors, whey protein
concentrate (WPC), fructooligosaccahrides (FOS) and
caseinomacro peptides (CMP) are used in dairy products
to enhance the growth and viability of the strains. Citrus
fiber in these products enhances bacterial growth and
survival of probiotic bacteria, whereas soy germ powder
releases bioactive compound that protect probiotic strains
from bile salt toxicity [9,10]. Recently, probiotic cheese,
marketed in various forms (fresh, semi-hard and hard
cheese), which are highly nutritious and have high energy
and fat content, has shown a high rate of survival of
probiotics at the end of its shelf life [11,12]. The utilization of
probiotics in the cheese faces some challenges, such as
low moisture content, the presence of salt, the development
of acid and the influence on flavor during maturation;
starter cultures can compete for nutrients and redox
potential. Nevertheless, it acts as a potential carrier of
probiotics [11]. Cheddar cheese, Feta cheese, Canestrato
pugliese hard Cheese, Cottage cheese, white-brined cheese,
Minas Fresco cheese, Minas fresh cheese, Argentine
Fresco cheese, Iranian white-brined Cheese, Turkish
Beyaz cheese are some of probiotic cheese products
available on the world market [12,13]. That having been
said, yoghurts with high fat content are the most common
vehicles for probiotics among dairy products. Probiotic
yoghurt contains cultures of L. acidophilus, L. delbrueckii
subsp. Bulgaricus and Streptococcus salivarius subsp.
thermophilus bacteria [14]. Some examples of Probiotic
yoghurt widely marketed for human consumption are
Corn milk yogurt [15]; Stirred fruit yogurts [13], Mango
soy fortified probiotic yogurt, Iranian yogurt drink (Doogh)
and Traditional Greek yogurt [12,16]. Other dairy-based
products, used to carry probiotics are ice cream and frozen
dairy desserts composed of milk proteins, fat and lactose
as well as other compounds that are required for bacterial
growth. These products are infused with certain
commercialized probiotic strains such as L. acidophilus
La-5 and B. animaliss sp. lactis Bb-12, L. acidophilus and
B. lactis. Probiotic chocolate mousse is a good medium
for L. paracasei subsp. paracasei LBC 82 which can exist
by itself or together with inulin.
Figure 1. Probiotic products (dairy and non-dairy products) available in the world market [4,7,8]

Journal of Food and Nutrition Research 215
Table 1. Probiotic products available in different countries [4,7,8]
Country
Probiotic products
Australia
F & N  s aLIVE fruit chunk yoghurt; Yo-plus digestive yoghurt; Wallaby organic yoghurt; Bio-life probiotic yogurt; Vaalia probiotic
yogurt; Ombar probiotic chocolate
Brazil
Chamyto probiotic drink ,Nestle; Actimel L. casei Defensis; Danito L. casei Danone, Sofyl yakult
Canada
Bio Best Plant Steroid probiotic yoghurt; kraft LiveActive cheddar cheese and Chocolate Raspberry Bars; liberte yoghurt, Olympic
Natural No Fat Probiotic yoghurt
Denmark
Klover drinkable yoghurt; Danimal Lactobacillus GG; Probio Arla cultura
Europe
Life way kefir; Culturelle probiotic Infant Formula; France Bravo Friscus; Yoplait yogurt; Danone Activia; Actimel probiotic yoghurt
Finland
Valio Gefilus® and Valio Kidius Gefilus® and Evolus® Milk drink and yoghurt (LGG); Yosa yoghurt oat product
France
b-Activ LGG Dukat Yoghurt and drink
Germany
Probiotic Vitality yoghurt; Soyoghurt
India
Nesvita’ Probiotic yoghurt (Nestle, India); Probiotic Ice-cream ‘Amul Prolife’ (Amul Dairy, India); ‘b-Activ’ Probiotic Dahi (Mother
Dairy); Probiotic curd Heritage Foods(India)ltd
Italy
Ganeden BC30® probiotic low fat yogurt; Probiotic dairy drinks Latteria Sociale Merano; Danacol fermented dairy beverage, Yolive
frozen yoghurt
Japan
Yakult; Meiji Bulgaria yoghurt and yoghurt drinks; Morinaga Bifidus yoghurt; Calpis Ameal S120
New Zealand
Biofarm Acidophilus Yoghurt
Spain
Kaiku Vita; Bio Herbal bifidus active green tea yogurt danone
Sweden
Provita yogurt; Yogenfruz yoghurt, biogia products; LiveActive probiotic products
USA
Activia Creamy yoghurt; Danone GYoPlus; Bluebunny-Sedona yoghurt Ice-cream; Chocolate Sweet Scoops-frozen yoghurt;
Yovation-pierra’s probiotic ice cream
UK
Vita-Yo creamy probiotic yoghurt; YeoValley Biolive yoghurt ; YeoValley natural fat free yoghurt; Unilever’s flora proactive
cholesterol
Table 2. Commercially available probiotic strains [5,6]
Probiotic strains
Source
Lb. acidophilus74-2; Lb.acidophilus 145; Lb. bulgaricus 1261; Lb. plantarumL2-1; Lb. rhamnosus 1091;
Lb. rhamnosus LC-705; Bifidobacterium species 420; Streptococcus thermophilus F2
Danlac (Canada)
Lb. fermentum RC-14 Urex Biotech (Canada)
Lb. casei 01; Lb. casei CRL431 Chr. Hansen (Denmark)
B. lactis Bb-12
Lb. acidophilus LA5
Lb. paracasei CRL 431
Lb. fermentum VRI003 (PCC) Lb. reuteri RC-14 ,
Lb. rhamnosus GR-1
Lb. paracasei F19
Chr. Hansen (Milwaukee WI)
Lb. acidophilus LA-1 Chr. Hansen, Inc. (USA)
Lb. acidophilus DDS-1 Nebraska Cultures, Inc. (USA)
Lb. crispatus CTV05 Gynelogix, Colorado (USA)
Lb. acidophilus
NCFM® Rhodia, Inc. (USA)
Lb. rhamnosus ATCC 7469
MicroBioLogics (MBL) (USA)
Lb. casei var. rhamnosus (Lactophilus)
Laboratoires Lyocentre (France)
Lb. caseiImunitass (Defensis, DN114, DN-014001)
Danone (France)
Lb. casei Shirota (YIT 0918) ; Bifidobacterium breve strain Yakult
Yakult (Japan)
Lactobacillus acidophilusCK120; Lb. helveticus CK60
Matsutani Chemical Product (Japan)
Bifidobacterium longum BB536 Morinaga Milk Industry Co., Ltd. (Japan)
Lb. acidophilus SBT-2062 ; Bifidobacterium longum SBT-2928
Snow Brand Milk Products Co., Ltd.
(Japan)
Lactobacillus acidophilusCK120; Lb. helveticus CK60
Matsutani Chemical Product (Japan)
Lb. paracasei F19
Arla Dairy (Sweden)
Lb. plantarum 299V ; Lb. rhamnosus 271 Probi AB (Sweden)
Lactococcus. lactis L1A
Essum AB (Sweden)
Lb. reuteri ATCC 55730
( “ Protectis ” )
Biogaia (Sweden)
Lb. salivarius UCC118
University College (Ireland)
Lb. johnsonii Lj-1(NCC533; Lb. acidophilus La-1)
Nestle (Switzerland)
2.1.1. Non-dairy Based Products
Non-diary based products are classified as fermented
and non- fermented products. A limitation in the use of
dairy products to deliver probiotics is due to the presence
of allergens. This led to the development of other food
matrices especially non-dairy probiotic products. Cereals
are good nutrient substrates for the growth of probiotic
strains. The fermentation of cereals in presence of
probiotic microorganisms could be beneficial for health
due to their availability of the vitamin B, the decrease of
non-digestible carbohydrates and the improvement of the
quality and level of lysine [17]. Boza is a fermented
product based on maize, wheat and other cereals containing
several lactic acid bacteria with probiotic characteristics.
Malt medium supports the growth of all examined strains
(L. plantarum, L. fermentum, L. acidophilus and L. reuteri)
better than barley and wheat media due to its chemical
composition. Malt, wheat and barley extracts exhibit a

216 Journal of Food and Nutrition Research
significant protective effect on the viability of above probiotic
strains under acidic conditions [12]. Oat, an important
cereal contains high levels of β-glucans and provides the
right nutrient for the growth of L. reuteri, L. acidophilus
and B. bifidum [18]. Probiotic cassava-flour product,
Starch-saccharified probiotic drink, Meat based products
and Dry-fermented sausages are also the name of some
other non-dairy probiotic foods [19,20]. Fruits are rich
in several nutrients such as minerals, vitamins, dietary
fibers, antioxidants and do not contain any allergens.
This advantage of fruits has encouraged several food
industries to manufacture healthy probiotic fruit juices like
pineapple, apple, orange, grape, watermelon juice, cranberry,
cashewapple juice, blackcurrant juice and many more.
L. plantarum, L. delbruekii, L. casei, L. paracasei and
L. acidophilus are main optimal probiotic bacteria widely
used for the production of probiotic juices [21]. Probiotic
beverage production from cashew apple juice fermented
with Lactobacillus casei NRRL B-442 whereas watermelon
juice is produced using four strains of Lactobacilli namely
Lactobacillus casei, L. acidophillus, L. fermentum and
L. plantarum. Probiotic tomato juice is produced by
inoculating lactic acid bacteria namely Latobacillus
acidophilus LA39, Lactobacillus plantarum C3,
Lactobacillus casei A4 and Lactobacillus delbrueckii D7.
Probiotic strains are able to grow without nutrient
supplementation and pH adjustment in the tomato juice
[22,23]. Similarly, probiotic bacteria such as L. plantarum,
L. casei and L. delbrueckii grow in both beet and cabbage
juices too [23,24]. Some examples of dairy and non
dairy-based probiotic products along with their probiotic
strains are listed in Table 3 and Table 4 [7,8,25,26,27].
Table 3. Probiotic products along with their respective strains
Probiotic products
Strains
Activia
B. animalis DN173010
Actimel
L. casei defensis
Attune nutrition bars
L. acidophilus NCFM, L.casei Lc-11 and B. lactis HN019
Align capsules
B. infantis 35624
Adult Formula CP-1
L. Acidophilus, L. Rhamnosus, L. Plantarum, B. Lactis and B. Bifidum
Batavito, Bob Sponja
L. casei
Biofibras B. animalis subsp. lactis L. acidophilus
Batavito, Bob Sponja L. casei
Biofibras
B. animalissubsp.lactis
L. acidophilus
Boza
Lb. plantarum, Lb. acidophilus, Lb.
fermentum, Lb. coprophilu s, Leuconostoc reffinolactis, Leuconostoc mesenteroides, Lb.brevis, Saccharomyce
scerevisiae, Candida tropicalis, Candida glabrata, Geotrichum penicillatum,Geotrichum candidum
Bio-K+ probiotic capsules L. acidophilus CL1285 and L. casei LBC804
Bushera
Lactobacillus, Lactococcus,Leuconostoc, Enterococcus and Streptococcus. Lb. brevis
Chamyto
L. johnsonii, L. helveticus
Culturelle capsules
L. rhamnosusGG
Danito
L. acidophilus, L. casei, B. animalis subsp.lactis
DanActive cultured milk
S. thermophilus and L. Bulgaricus in addition to L. casei DN-114 001
Gefilus juice
L. RhamnosusGG
Good Belly fruit drink
L. plantarum299v
Injera
L. plantarum, Aspergillus spp., Penicillium
spp., Rhodotorula spp., Candida spp.
Kishk, kushuk,
L. casei, L. plantarum, L. brevis, B. subtilis,
Kisra
L. plantarum, L. brevis
Kefir drinks
L. acidophilus, Lb. Brevis, L. casei, Lb.casei subsp. Rhamnosus, Lb. casei subsp. Pseudoplantarum, Lb.paracasei
subsp. Paracasei, Lb.delbrueckii subsp. Lactis
Lective
B. animalis subsp.lactis
Mahewu
Lactococcus lactis subsp. lactis
Nesvita
B. animalis subsp.lactis
OWP probiotics
B. longum, B. brevis, B.infantis, L. plantarum, L.rhamnosus, L. acidophilus
Sofyl
L. casei shirota
Togwa
Lactobacillus, Streptococcus, Lb.Plantarum A6
VSL#3 saket B. breve, B. infantis, B.longum, L. acidophilus, L.bulgaricus, L. casei, L.plantarum and S. thermophilus
Yakult cultured milk L. casei Shirota
Yo-Plus yogurt
B. animalis subsp lactis
Bb-12;
S. thermophilus
and
L. bulgaricus
Table 4. Non-Dairy formulations containing Probiotic strains
Foods Examples Probiotic strains
Cereal based Wheat, Malt, maize, oat L. plantarum, L. fermentum, L. acidophilu sand L. reuteri
Fruit juices
Pineapple, apple, orange, grape, watermelon
juice, cashew apple juice and blackcurrant juice
L. plantarum, L. delbruekii, L. casei, L. paracasei. L. fermentum, L. plantarum and
L. acidophilus
Vegetable
juices
Beets-based drink, tomato-based drink, cabbage
juice, carrot juice and banana puree
Latobacillus acidophilus LA39,Lactobacillus plantarumC3, Lactobacillus casei
A4, Lactobacillus delbrueckii D7 and Lactobacillus plantarum 299v (LP299V®)

Journal of Food and Nutrition Research 217
2.1.2. Encapsulated, Spore Germinated and
Genetically Engineered Probiotic Products
Micro-encapsulation serves as an important means for
the survival of the probiotic cells. The encapsulated cells
are introduced into different food matrices e.g. Yoghurt,
cheddar cheese, ice-cream, yogurt-covered raisins, nutrient
bars, chocolate bars, cocoa butter, biscuits, vegetable and
frozen cranberry juice [28,29]. The encapsulated probiotic
cells available in a tablet/capsule form are Forever Active
Probiotic, Probiotic 7, Multi-probiotic or in the form of a
powder e.g. Pure Baby Probiotic, Cernivet LBC ME10,
Geneflora™ and ThreeLacTM. Additionally, Probio-Tec
capsules, encapsulated probiotic orange juice termed
“Dawn”, chocolate bar named “Attune”, Innovance
Probiotiques and an encapsulated yoghurt is available in
the market under the brand name Doctor-Capsule. Syntol
AMD and Ganeden BC30 deliver probiotic spores rather
than living bacteria is known to be spore-germinated
probiotics prepared by using spore germination technology.
Though the use of these genetically engineered products
has been quite limited but certain genetically modified
probiotics strains have been used to increase physiological
or immunological properties within the organism
which can be useful in mucosal delivery system or in
development of vaccine vector [30]. The use of any
engineered strains has to be rigorously assessed for its
safety before human use.
2.2. Mechanisms of Action of Probiotic
Strains
About 10 trillion microbes of 500-1000 different microbial
species colonize in the GI tract and remain in a complex
equilibrium. These include Bacteroides, Lactobacillus,
Clostridium, Fusobacterium, Bifidobacterium, Eubacterium,
Peptococcus, Peptostreptococcus, Escherichia and Veillonella.
Colonization of these microbes in the human gut start at
birth and eventually get exposed to foreign microbial
population and antigens derived from digested foods.
Therefore, the intestine acts as an interface between the
host and exogenous agents such as, pathogenic bacteria,
viruses, allergens. The intestinal mucosa may play a
central role in host microbiota-pathogen interactions [31].
Gut microbiota influences human health through an
impact on the gut defense barrier, immune function, and
nutrient utilization and potentially by direct signaling with
the gastrointestinal epithelium [32]. The interaction
between the host microbata and exogenous agents may
disturb or alter the normal microbial balance or their
activity in GIT. Alteration of such microflora is implicated
in the pathogenesis of various diseases. Enteric diseases
are caused by several pathogens like Escherichia coli,
Salmonella spp., Shigella along with various other food
borne pathogenic strains such as Bacillus cereus,
Staphylococcus aureus, Listeria monocytogenes and
Vibrio cholera [33]. They may cause infections in two
steps. During the first step of the infection process, the
pathogens may attach themselves to the surfaces of
intestinal epithelial cell through certain adhesive receptors
like glycoproteins and glycolipids and later on, in second
step they cause direct cytotoxic injury, intracellular
migration, and finally disrupt the epithelial tight junctions
that leads to mucosal infection [34].
Probiotics promote the GIT homeostasis and stimulate
the growth of indigenous beneficial gut microbata by
inhibiting the growth of pathogenic or opportunistic
pathogenic microbes. Therefore, probiotics are recommended
as alternative bio therapeutic agents for intestinal
pathogenic infections. These may act via several mechanisms
such as, production of antimicrobial compounds, competition
for nutrient substrates, competitive exclusion, enhancement
of intestinal barrier function and immunomodulation
[1,35,36,37].
2.2.1. Production of Antimicrobial Substances
LAB produces antimicrobial substances, such as
organic acids, fatty free acids, ammonia, hydrogen
peroxide and bio surfactant. It also produces a
low-molecular-weight antibacterial peptide- bacteriocins
that inhibits both gram positive and gram-negative enteric
pathogens [38,39]. For example, probiotic L. rhamnosus
GG inhibits the growth of pathogenic Salmonella enterica
by producing lactic acid and other secreted antimicrobial
molecules [40]. In order to exert a strong effect on a
pathogen in vivo, the probiotic-derived antimicrobial
compounds are produced in the right location in the
intestinal tract at higher levels. Organic acids produced by
LAB or any probiotic strains account for the alteration of
bacterial flora due to the acidification of the colon by
nutrient fermentation.
Homo-fermentative LAB strains produce lactic acid
whereas hetero-fermentative strains produce the short
chain fatty acids viz. acetic and propionic acids in addition
to lactic acid by their respective metabolic pathways.
Organic acids produced by certain probiotic strains lower
the external pH that causes acidification of the cell
cytoplasm. Nevertheless, these acids are partially in their
undissociated at lower pH values. The undissociated
organic acids are lipophilic and diffuse passively across
the membrane that may cause intracellular acidification.
On the contrary, at high intracellular pH values, they
dissociate to produce hydrogen ions that interfere with
essential bacterial metabolic functions. It also denatures
protein and collapses the electrochemical proton gradient
resulting in the disruption of substrate transport systems of
infectious pathogens. Thus, it also alters the cell
membrane permeability of pathogenic bacteria [41].
Production of free radicals along with hydrogen
peroxide (H2O2) acts as a precursor that damages the DNA.
In certain cases, the antimicrobial activity of H2O2 may
result from the oxidation of sulphydryl groups thereby
causing denaturation of a number of enzymes. The
peroxidation of membrane lipids by H2O2 also causes the
increased membrane permeability [41]. Carbon dioxide
(CO2) as end products of fermentative metabolism creates
an anaerobic environment that may inhibit enzymatic
decarboxylation reaction. In certain cases, it causes a
malfunction in permeability due to the heavy
accumulation of CO2 in the membrane lipid bilayer. LAB
also produces significant amounts of fatty acid, named as
Reuterin, that show their antimicrobial potential under
specific conditions [41]. Lactobacillus paracasei produces
certain bactericidal bio surfactant that inhibits the growth
of several pathogens [39].

218 Journal of Food and Nutrition Research
2.2.2. Bacteriocins (Antimicrobial peptide)
Bacteriocins are ribosomally synthesized low-
molecular-weight antimicrobial peptides with a good
functional therapeutic activity against gastrointestinal
pathogenic infections [42,43]. Bacteriocin activity adsorbs
specific or non-specific receptors on the target cell surface
and alters the membrane permeability, thus disturbing
membrane transport, and finally inhibiting energy
production. Numerous bacteriocins, such as nisin,
lactobrevin, acidophilin, acidolin, lactobacillin, lactocidin
and lactolin have been reported to be produced by
Lactobacilli [42,43,44]. Table 5 presents the class of
bacteriocins and its characteristics, based on structural,
physicochemical and molecular properties.
Antimicrobial peptides (AMP) get attached to the
anionic components of bacterial cell wall because of their
cationic nature and cause disruption of cell envelope to
reach into cytoplasmic membrane in a process known to
be self-promoted uptake. A numbers of models including
barrel stave model, carpet, toroidal or aggregate channel
model represent different mechanisms of action. AMP
become stave in a barrel like cluster around the outer
membrane of pathogenic flora and the hydrophilic
surfaces of peptides point facilitate pores. Leakage of
cellular components through these transmembrane pores
depletes proton motive force that ultimately interferes
with cellular biosynthesis causing cell death [44,45].
2.2.3. Colonization Resistance and Competitive
Exclusion
Adherence to human intestinal cells and intestinal mucus
glycoproteins (mucin) as well as competitive exclusion of
pathogens are most important characterization of probiotic
strains to deactivate the pathogen in the intestine. Such
competition may occur either for adhesion or for
nutritional substrates and biogenic growth metabolites.
Infection begins with the binding of the pathogen to
intestinal epithelial cells via carbohydrate moieties of
glycoconjugate receptor molecules. Probiotic strains
compete with invading pathogens for the glycoconjugate
receptors at the infection site of intestinal epithelium cells,
which may block adhesion and penetration of infectious
pathogens [46]. Gastrointestinal cell surface constituents,
such as several glygoconjucates, can serve as receptors for
bacterial adherence [47]. Adhesion may be specific or
non-specific based on physico-chemical factors and
involves adhesin molecules on the surfaces of adherent
bacteria and receptor molecules on epithelial cell.
Probiotic agents also compete for receptors or adhesion to
intestinal epithelium that could prevent the colonization of
pathogenic microorganisms from occupying this living
space (colonization resistance or competitive inhibition)
[36]. Escherichia coli binds to epithelial cells via mannose
receptors in human intestinal epithelial cells; Probiotic
L. acidophilus ATCC 4356 has shown similar adherence
capabilities that could inhibit pathogen colonization at the
same sites, thereby protecting the host against the
infection [48,49].
Probiotics may also compete for an ecological niche
creating an unfavorable condition for the invading
pathogens to take hold in the intestinal tract and impair
their colonization ability. A competition for nutritional
substrates and biogenic growth metabolites (amino acid,
methylamines, vitamins, short-chain fatty acids (SCFA)
and bioactive peptides) amongst intestinal microbiota,
probiotics and pathogens may occur. Bifidobacterium
adolescentis S2-1 can better utilize vitamin K and inhibit
the growth of Porphyromonas gingivalis by competing for
the growth factor [50]. Lactobacillus plantarum 423 is
able to colonize intestinal epithelial cells, thus preventing
the adhesion of pathogenic Clostridium sporogenes and
Enterococcus faecalis [46].
2.2.4. Intestinal Barrier Function
The mucus layer is the first line barrier where
pathogens penetrate it to reach the epithelial cells during
infection, thus it provides protection by shielding the
epithelium from potentially harmful antigens [51].
Disruption of epithelial barrier function or a loss of tight
junction formation in the intestinal epithelium cells are
another major reasons of intestinal pathogenic infections.
Probiotics maintain a tight junction protein expression and
enhancement of host mucin production, which improves
the ability of the mucus layer to act as an antibacterial
shield by preventing the increase of apoptotic ratio
[36,52,53]. Probiotics can reduce the epithelial injury that
follows exposure to E. coliO157:H7 and E. coli O127:H6
[54].
2.2.5. Immunomodulation
Several studies have shown an interesting physiological
action of probiotics that modulate the immune system.
Probiotics might be able to modulate the host's defenses
including the innate as well as the acquired immune
system [55]. One of the more precise mechanisms of
action of probiotics is modulation of GI immunity by
altering inflammatory cytokine profiles and down
regulating proinflammatory cascades [56]. They enhance
the production of serum IgA secretory IgA, as well as
natural killer cells and phagocytosis, which play a crucial
role in intestinal immunity. They prevent apoptosis and
suppress T cell proliferation, thus preventing various
inflammatory conditions [56,57,58]. Lactobacillus reuteri
strains from human breast milk, either stimulate the key
pro inflammatory cytokine, human tumor necrosis factor
(TNF), or suppress its production by human myeloid cells
[56,58]. Both in vitro production of g-IFN, IL-12, and
IL-18 by lymphocytes and enhanced capacity to produce
g-IFN in response to different lactic bacteria strains.
L. paracasei is a potent stimulator of IL-12. However,
IL-12 may down regulate the Th-2 response, decreasing
IL-4 and IgE production. It may prevent an allergic
tendency in humans.
Probiotics can also modulate toxin receptors and
block toxin-mediated pathology by using enzymatic
mechanisms. For example; S. boulardii degrades
Clostridium difficile toxin receptors and blocks
cholera-induced secretion in rat jejunum by the production
of polyamines [59]. The presence of several probiotic
bacteria regulate human beta defensin 2 (hBD-2) via the
transcription factor NF-κB that would strengthen intestinal
defenses [60].

Journal of Food and Nutrition Research 219
Table 5. Classification of Bacteriocin
Class Characteristics Bacteriocin produced FDA Approved
Class I
 small, cationic, hydro-phobic and heat-stable peptides.
 usually contain unusual amino acids (e.g. the thioether amino
acids lanthionine and/or 3 -methyl-lanthionine)
 Lantibiotics
 Nisin No
Yes
Class II  small, cationic, heatstable peptides
 Pediocin PA-1.
 Mesentericin Y105
 Enterocin P, A

Curvacin A.
No
Class III  large, heat-labile proteins
 Helveticin J
 Lectacins A and B
No
Class IV  Complex
 Sublancin
 Glycocin F
No
2.3. Clinical Implications of Probiotics
in Gut Health
A disturbed gut microflora, results in a wide range of
symptoms, compromising the gut health and resulting
in gastroenteritis. Gastroenteritis is caused by several
pathogens such as Shigellae, Salmonellae, Escherichia
coli, Vibrio cholera, and Clostridium, which may first
colonize and then grow in the gastrointestinal tract. Then
they invade the host tissue, or may secrete toxins that
disrupt the function of the intestinal mucosa and normal
gut flora (both their activity and balance) causing nausea,
vomiting and diarrhea.
Diarrhea has become a foremost global health problem
of late. It may be classified as (1) acute diarrhea (duration
is less than 2 wk), (2) persistent diarrhea (duration varies
from 2 to 4 wk), and (3) chronic diarrhea (duration is more
than 4 wk). In many developing countries, infectious
gastroenteritis such as shigellosis, traveller’s diarrhea
(TD), antibiotic associated diarrhea (AAD), acute diarrhea
(AD), inflammatory bowel syndrome and irritable bowel
syndrome are the common fatal diseases caused by more
than 50 different pathogens including virus, bacteria,
fungus and protozoa. Rotavirus and entero pathogenic E.
coli (EPEC) are the leading causes of endemic pediatric
diarrhea and Traveller’s diarrhea. They affect all age
groups. It has been estimated that severe enteric pathogenic
diarrhea and dehydration are the main cause of morbidity
and mortality each year worldwide [61]. Evidence
suggests that oral consumption of microorganisms may
have some preventive as well as curative effects on the gut
flora [62]. They have a long history of safe use in foods
and exert antagonistic effects on the growth of invasive
and opportunistic pathogenic bacteria such as
Staphylococcus aureus, Salmonella typhimurium, Shigella,
Yersinia enterocolitica, Vibrio cholera and Clostridium
perfringens [63].
2.3.1. Salmonellosis
Salmonellosis is an important health concern caused by
Salmonella. A protective role of probiotic stains such as
Lactobacillus acidophilus Bar13, L. plantarum Bar10,
Bifidobacterium longum Bar33, Enterococcus faecium
PCD71 and Lactobacillus fermentumACA-DC179 and B.
lactis Bar30 strains suppress the growth of Salmonella
typhimurium and S. enteritidi [64,65,66].
2.3.2. Antibiotic-associated Diarrhea (ADD)
Diarrhea is the most common gastrointestinal side
effect of antibiotic therapy often associated with
C. difficile infections in adults and children. Certain drugs
(ampicillin, amoxicillin, cephalosporins and clindamycin)
cause changes in the composition of intestinal microflora
resulting in the proliferation of bacterial strains such as
C. difficile, C. perfringens type A, S. aureus, K. oxytoca,
Salmonella spp., Candida spp. The opportunistic
proliferation of intestinal pathogens after breakdown of
colonization resistance due to antibiotic administration
releases two protein exotoxins, toxin A and toxin B
responsible for diarrhea and colitis [67].
The role of probiotic strains of Lactobacillus
(L. rhamnosus), Lactococcus spp., Leuconostoc cremoris,
Bifidobacterium species, Bacillus spp., Saccharomyces
spp., or Streptococcus spp. probiotics strains have
been reported as a complementary therapy in the treatment
of ADD [2,68]. The antimicrobial substances produced
by Lactobacillus GG show a broad-spectrum activity
against infectious C. difficile bacteria to control ADD.
The most commonly used probiotics are administered
as doses from 107 to 1011 for durations ranging from
5-49 days, generally paralleling the duration of antibiotic
therapy [69] (McFarland, 2009). It was reported that
after the completion of antibiotic therapy, administration
of a mixture of certain probiotic strains notably, L. casei,
L. bulgaricus, and S. thermophilus reduced the incidence
of AAD [70]. The combination of two Lactobacillus
strains, L. acidophilus and L. casei has been proved to be
an effective oral therapy in the treatment of antibiotic
associated diarrhea [71].
2.3.3. Traveller’s Diarrhoea (TD)
TD commonly affect is healthy travelers in developing
countries characterized by the excretion of a minimum
of three unformed stools per day. Table 6 presents
the classification of E. coli. E. coli produces one or
more Shiga toxins that induce production of lesions on
host intestinal epithelial cells, thus reducing intestinal
epithelial barrier function [72]. Enteropathogenic E. coli
(EPEC), rarely Campylobacter, Shigella and Salmonella
are the main causative agent of TD responsible for
inconvenience and discomfort [73]. In different clinical
studies, the prevention of TD by the administration of
L. acidophilus, L. bulgaricus, Streptococcus thermophilus
and S. cerevisiae exhibit the antimicrobial potency of
probiotics. Lactobacillus GG strains in a dose of 2 × 109
CFU for two weeks and S. boulardii probiotic yeast
5×109 - 1×1010 CFU for three weeks are effective against
TD [74].

220 Journal of Food and Nutrition Research
Table 6. Classification of Diarrheagenic E.coli
Categories
Enteropathogenic E. coli (EPEC)
Enterotoxigenic E. coli (ETEC)
Enteroinvasive E. coli (EIEC)
Enteroaggregative E. coli (EAggEC)
Enterohemorrhagic E. coli (EHEC)
Diffusely adherent E. coli (DAEC)
2.3.4. Acute Diarrhea
Acute diarrheal infection by rotaviruses is a major
health problem worldwide. Acute diarrhea is defined as
more often than usual bowel movements lasting 10-14
days. In a randomized study, it was reported that number
of infectious pathogens like rotavirus, adenovirus,
Salmonella spp, Escherichia coli, Yersinia enterocolitica,
Clostridium difficile, parasitices (Giardia lamblia,
Cryptosporidium parvum) are the main cause of this
diarrhea [75]. Rotaviruses invade the columnar cells
of the small intestinal epithelium where they replicate
resulting partial disruption of the intestinal mucosa with
loss of microvilli and increase intestinal permeability.
Lactobacillus rhamnosus GG, L. casei Shirota, L. reuteri,
L. acidophilus spec., Bifidobacterium animalis ssp. Lactis
BB-12, Enterococcus faecium SF68, Saccharomyces
boulardii are some of best-documented probiotic strains
effective against acute diarrhea [76,77].
The mechanisms of actions by which Lactobacilli and
Bifidobacterium bifidum reduce rotavirus-induced diarrhea,
includes production of antimicrobial compounds,
enhancement of the immune response and competitive
blockage of receptor sites when lactobacilli bind to
receptors [1,78]. The treatment with Lactobacillus GG
promotes systemic and local immune response to rotavirus
by enhancing IgA specific antibody-secreting cells (sASC)
and serum IgA antibody level at convalescence, thereby,
strengthening the gut immunological barrier. An analysis
of the impact of probiotic strains as a milk supplement
shows Bifdobacterium lactis in an amount of 1.9 × 108
CFU per 1 g of powder milk reduces the risk of rotavirus
infection [79].
2.3.5. Helicobacter Pylori Gastroenteritis
Helicobacter pylori is an important etiologic agent of
chronic gastritis, gastric and duodenal ulcers and increases
the risk of gastric cancer as well as stomach carcinoma.
Pathogenic H. pylori produces urease, which can
hydrolyse urea to ammonium resulting in elevated pH in
the stomach [81]. Clinical studies have established the
value of probiotics, viz., Lactobacillus acidophilus,
L. casei strain Shirota and Lactobacillus fermentum etc
in treatment of Helicobacter pylori gastroenteritis [80]. In
addition, the outcome of using a probiotic combination of
Lactobacillus rhamnosus GG, L. rhamnosus LC705,
Propionibacterium freudenreichii JS and Bifidobacterium
lactis Bb12 for 8 weeks decreases urease and gastrin-17
activities found in H. Pylori-infected patients; whereas the
probiotic Lactobacillus reuter suppresses H. pylori
binding to the glycolipid receptors [82].
2.3.6. Inflammatory Bowel Syndrome
Inflammatory bowel syndrome (mainly Crohn’s disease
and ulcerative colitis) is more common among young
people. Crohn’s disease (CD) is chronic and idiopathic
inflammation occuring from the mouth to the anus with
the terminal part of the ileum mainly affected. Crohn’s
disease is associated with impairment of the barrier function
and causes inflammation that extends much deeper into
the layers of the intestinal wall. In general, it tends to
involve the entire bowel wall, whereas ulcerative colitis
affects only the lining of the bowel with characteristic
patchy transmural lesions containing granulomas [83,84].
Ulcerative colitis is a chronic inflammatory disease of the
inner lining (mucosa membrane) of the intestine or colon
whereby, the colon becomes inflamed (red and swollen)
and causes necrosis, ulceration (open, painful wounds),
and perforation of the intestine along with diarrhea. Blood
and mucus is f found in feces [83].
The administration of a formulated VSL#3 consisting
of 8 probiotic strains (L. acidophilus, L. casei, L.
delrueckii subs. bulgaricus, L. plantarum, B. breve, B.
longum, B. infantis, and Streptococcus salivarius subs.
thermophilus) in the amount of 3.6 × 1012 CFU twice daily,
for 12 weeks provides a notable improvement in ulcerative
colitis [85]. Moreover, inflammatory bowel syndrome
diseases show a positive response to probiotics such as
LGG, E. coli, Nissle1917,or a mixed culture preparation,
containing 4 strains of Lactobacilli, 3 strains of
bifidobacteria, and Streptococcus thermophilus (VSL#3)
[86]. Studies on probiotic, VSL#3 for 9-12 months have
reported a positive outcome in the prevention and
treatment of pouchitis [87,88].
2.3.7. Irritable Bowel Syndrome (IBS)
Irritable Bowel Syndrome (IBS) is the most common
functional gastrointestinal disorder with a collection of
symptoms such as abdominal pain, bloating, incomplete
evacuation, intestinal gas, straining, bowel function and
constipation. The altered microflora or induction of an
altered inflammatory state in the bowel may lead to
malabsorption of bile acids in the colon and increased
fluid and mucus secretion through the mucosa resulting
in diarrhea and IBS symptoms [89]. This disease is
chronic and 20% of adults, especially the women are
predominantly affected. Bifidobacterium infantis 35624,
E. coli Nissle1917, Lactobacillus GG and L. plantarum
299 v (Lp 299 v) are efficient against IBS [90,91,92].
3. Conclusion
The uses of probiotics in foods in on the rise and is
gradually attracting attention. The applications of
probiotics in food to preserve a healthy gut are one of the
viable methods to maintain good health. The proposition
of different foods as a vehicle to transfer probiotics in the
body is a sustainable method. However, strain selection,
processing, inoculation of starter cultures and selecting
appropriate foods as a vehicle, needs strict regulations for
transfer of health benefits to humans. Further studies are
required to validate the interactions between probiotics,
gut microflora and the gastrointestinal tract, across all

Journal of Food and Nutrition Research 221
ages of the lifespan. Identification of new variants of
probiotics derived from the microbiomes may be a good
strategy to promote gut health in future.
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