• Concept of probiotics
• MOA and examples of probiotics
• Prebiotics and its examples
• Clinical applications of pre/pro biotics
• Current status of probiotics in India
Intestine is a Paradise of disease
• Death sits in
the bowels; a
is the root of
all evil” -
History of Probiotics
• At the start of the 20th century, Russian Nobel prize
winner and father of modern immunology, Elie
Metchnikoff , a scientist at the Pasteur Institute,
was the first to conceptualize “Probiotics”
• In early 1930’s, in Japan, Minoru Shirota
developed a fermented milk product called
Yakult with a special strain of Lactobacillus
• The word “probiotic” (origins: Latin pro
meaning “for” and Greek bios meaning “life”)
was first used to indicate substances that
were required for a healthy life
• Probiotics term coined in 1965 by Lilly And
Largest immune organ
• It participates in protection of the host through strong
defense mechanisms from the external environment
• Defense task is based on three barriers:
• 1- The ecological barrier (normal inhabitant flora within intestine)
• 2- Mechanical barrier (mucous epithelia)
• 3- Immune barrier (GALT, secretory IgA, intraepithelial lymphocytes,
macrophages, neutrophils, natural killer cells, Peyer’s patches and mesenteric
• Our Intestine = 400 square meter surface…
i.e. the surface area of a tennis court
Facts about Intestine
• Trillions living bacteria exist
in the human intestine
• We have more bacteria in our
bodies (10 times greater) than
the total number of our
somatic and germ cells
• We carry about 2 kg of
• Over 500 species of bacteria
present in human colon.
and Acidophilus comprise the
majority of healthy bacteria in
the colon along with other
disease producing bacteria.
Factors affecting the intestinal micro
• During infancy :
Mode of delivery
• Later in life :
Antibiotics and other drug intake
Diet (highly processed, low fiber)
Dysbiosis is the abnormal microbial
colonization of the intestine ,
where changes in Quantity and
Quality of flora become
Pathological & Harmful.
Common causes of dysbiosis:
• Antibiotic therapy
• Autoimmune conditions , IBD
• Others are fast paced lifestyle,
stress, food habits, Alcohol intake and
The term “Nutraceutical” was coined from
“Nutrition” & “Pharmaceutical” in 1989 by
Stephen De Felice.
Nutraceutical can be defined as
“ A food or part of food or nutrient, that
provides health benefits, including the
prevention and treatment of a disease.”
Includes :- GE foods, cereals supplemented with
vitamins or minerals, genetically manipulated
soybean and canola oil without trans-fatty acids
Classification of nutraceuticals
Based on chemical constituents:
– Nutrients :- Substances with established nutritional
functions, such as vitamins, minerals, amino acids and fatty
– Herbals :- Herbs or botanical products as concentrates and
extracts, such as aloe vera juice, evening primose oil
– Dietary Supplement :- products that contain a dietary
ingredient intended to add something to the foods we eat
such as prebiotics, probiotics
Defining a probiotic
which when administered
in adequate amounts
confer a health benefit on
Why are Probiotics important for Human health?
gut micro flora
nutrients in the
Key properties of probiotic
Non-pathogenic, non-toxic and non-allergic.
Capable of surviving and metabolizing in upper G.I.
tract e.g. Resistant to low pH, organic acids, bile juice,
saliva and gastric acid
Human in origin, genetically stable and capable of
remaining viable for long periods in field condition.
Able to modulate immune response and provide
resistance to disease through improved immunity or by
the production of antimicrobial substance in the guts.
Key properties of probiotic
Good adhesion/ colonization to human intestinal tract
and influence on gut mucosal permeability.
Antagonistic against carcinogenic/ pathogenic
Clinically proven health benefit, e.g. gastrointestinal
disorders, diarrhoea, clostridium difficle colitis,
antibiotics associated diarrhoea, acute gastroenteritis.
Technologic properties for commercial viability such as
stability of desired characteristics during processing,
storage and transportation.
Examples of probiotics
Non pathogenic Escherichia coli
Saccharomyces cerevisiae (yeast)
L. casei (rhamnosus)
Mechanism of action
Bioconversion of, for example, sugars into fermentation
Production of growth substrates, like vitamins B and K, for
Direct antagonism by antimicrobial substances:
– hydrogen peroxide
– organic acids
Mechanism of action
Competitive exclusion for binding sites
Improved barrier function
Production of β- D- galactosidase enzymes that
break down lactose .
Reduction of inflammation, thus altering
Stimulation of innate immune response
food allergy symptoms
Control of IBD
(Bile acid deconjugation
Probiotic products marketed in
India is an emerging market for probiotic
products, being the largest producer of
Amul , Mother dairy, Nestle Nesvita
(first India’s Dahi with probiotics) and
Yakult are the major brands.
Streptococcus faecalis T-110 30 million
Clostridium butyricum TO-A 2 million
Bacillus mesentericus TO-A 1 million
Lactobacillus sporogenes 50 million
The concept of prebiotic was introduced by
Gibson & Roberfroid, in 1995
“Non-digestible food ingredients that
beneficially affect the host by selectively
stimulating the growth and/or activity of one
or a limited number of bacteria in the colon
that can improve host health."
Name Obtained from/manufactured by
Inulin Extraction from chicory root, Wheat, banana, onions,
Fructo-oligosaccharides Tranfructosylation from sucrose, or hydrolysis of chicory
Galacto-oligosaccharides Produced from lactose by b-galactosidase, milk
SOS (soy-oligosaccharides) Extracted from soya bean whey
XOS (xylo-oligosaccharides) Enzymic hydrolysis of xylan
IMO (isomalto oligosaccharides) Transgalactosylation of maltose
Pyrodextrins Pyrolysis of potato or maize starch
Breast Milk oligosaccharides They represent the third largest
component of Human Milk 20 - 23 gm/l in colostrum & 12- 14 gm/l in
Clinical application of probiotics and
• Diarrheal Illness - treatment and prevention
• Prevention of antibiotic-associated diarrhea (AAD)
• Treatment of Clostridium difficile infection
• Inflammatory bowel disease (ulcerative colitis,CD)
• Lactose intolerance
• Necrotizing Enterocolitis (NEC)
• Food allergies
Probiotics in the Treatment of Gastrointestinal
Antibiotic associated diarrhea
Broad-spectrum antibiotics are associated with
the highest rate of AAD because of their
disruptive impact on the normal intestinal flora.
Commonly implicated antibiotics – broad spectrum
penicillins (ampicillin), Cephalosporins
(Cefixime,cefalexin), Clindamycin, Fluroquinolones.
Diarrhea is a common adverse effect of antibiotic treatments.
Antibiotic associated diarrhea occurs in about 5-30% of patients
Probiotics used in prevention and as adjuvant therapy in AAD.
Antibiotic associated diarrhea
Disease Antibiotic treatment
Microbiota Clostridium overgrowth
in balance produces toxin
Lactase digests lactose commonly present in milk
and milk products.
Lactose is not digested when there is a
deficiency in lactase and results in diarrhea.
Supplementation with probiotics has been shown
to mitigate the symptoms of lactose intolerance
by enzyme β- D- galactosidase.
Having yoghurt is a good way for a lactose
intolerant person to get calcium.
Helicobacter pylori Infections
Chronic gastritis, Peptic ulcers, Gastric
adenocarcinoma, and a number of non-gastrointestinal
Bifidobacteria and B. subtilis may inhibit the growth
or attachment of H. pylori.
Possible mechanisms eradicates H. pylori include
the ability of the probiotics to bind to gastric epithelial
to produce a high quantity of lactic acid, and
to proliferate rapidly.
Lactic acid bacilli
Increases production of
Short chain Fatty Acid
Inhibits cholesterol syn
Decreases blood chlesterol
Bile syn. Increases
More cholesterol is used up
Probiotics and Cancer
Enzymes (Glycosidase, B- glucuronidase , azoreductase ,
and nitroreductase) of the intestinal flora convert the
precarcinogens to active carcinogens giving rise to
Faecal concentrations of enzymes
Reduce absorption of harmful mutagens that may
contribute to colon carcinogenesis.
Activity of L. acidophilus and L. casei supplementation
in humans helps to decrease levels of these enzymes
Dosage of Probiotics
The dose of probiotics is usually expressed as the
number of colony forming units (CFUs).
Due to the multitude of strains, the FDA has not
approved any specific health claims for probiotics.
The varying strains also make it impossible to
establish an RDA for a probiotic.
Probiotic effects should be considered dose-specific
Dose listed on the label are based on studies that
show a beneficial health effect in humans.
Prebiotics vs Probiotics
Prebiotics are defined as nonliving
non-digestible special form of fiber
Probiotics are referred to as live
active microorganisms that when
administered in adequate amount will
have beneficial effects to its host.
The powder form of prebiotics
can survive heat, cold, acid.
• more fragile.
• vulnerable to heat.
• may be killed over time.
Prebiotics perform their role by
nourishing the bacteria that live
in the intestines.
Probiotics fight the harmful
bacterial species present in the
Probiotics side effects, if they occur, tend to be mild
and digestive symptoms. (such as gas or bloating).
May cause infections, especially in immuno-compromised
Diabetic patients should be doubly cautious about
taking probiotic drinks available in the market as they
contain high level of sugar.
Probiotic products taken as a dietary supplement are
manufactured and regulated as functional foods, not
Are probiotics supplements
Probiotics supplements are not necessary for normal,
In healthy individuals, daily consumption of
probiotics rich foods, particularly fermented dairy
products like yoghurt adequately supplies the amount
of probiotics required to maintain a healthy digestive
system and overall wellbeing.
A diet high in starches and fibre provide prebiotics,
which keep a healthy population of probiotics in our
Synbiotic = Probiotic + Prebiotic
The concept of synbiotics has been proposed to
characterize health-enhancing foods and supplements
used as functional food ingredients in humans
Potential synergy between pro- & prebiotics
Improve survival in upper GIT
More efficient implantation
Eg: Bifidobacteria and fructo-oligosaccharides (FOS)
Health benefits of Synbiotics
• Improved survival of live bacteria in food products,
prolonged shelf life
• Increased number of ingested bacteria reaching the
colon in a viable form
• Stimulation in the colon of the growth and
implantation of both exogenous and endogenous
• Activation of metabolism of beneficial bacteria,
antagonistic toward pathogenic bacteria
Increased from $14.9 billion in 2007 to an
estimated $15.9 billion by the end of 2008.
It is expected to reach $36.7 billion by
2018, a compound annual growth rate
(CAGR) of 6.2%.
Japan accounted for the largest share of
total sales in 2007 with 39.5%, driven
primarily by the country’s large and well-developed
probiotic foods segment.
Status of Probiotics in India
• Indian probiotic industry is in its infancy
stage and presently accounts for only a small
fraction i.e. less than 1% of the total world
market turnover in the probiotic industry.
• Apart from human use, also used as animal
feed supplements for cattle, poultry and
• The latest and recent addition to the list of
probiotics in India is ViBact (which is made up
of genetically modified Bacillus mesentricus),
which acts as an alternate to B-complex.
Institutes engaged in Probiotic research
Central Food Technology And Research Institute,
National dairy research institute, Karnal, Haryana, India
• Institute of microbial technology, Chandigarh, India
• National dairy development board, Anand, Gujarat,
Nestle Pvt Ltd, Panipat, Haryana, India
Human Microbiome Project
The Human Microbiome Project (HMP) 2008,
aims to characterize the microbial communities
found at several different sites in the human
body, including nasal passages, oral cavities,
skin, GI tract, and urogenital tract, and to
analyze the role of these microbes in human
health and disease.