Dr Soumya

Junior Resident
 Overview
• Introduction
• History
• Concept of probiotics
• MOA and examples of probiotics
• Prebiotics and its examples
• Clinical applications of pre/pro biotics
• Synbiotics
• Current status of probiotics in India
• References
Intestine is a Paradise of disease

• Death sits in
the bowels; a
bad digestion
is the root of
all evil” -
Hippocrates,
400 BC
 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”
 History contd.
• In early 1930’s, in Japan, Minoru Shirota
developed a fermented milk product called
Yakult with a special strain of Lactobacillus
casei shirota.

• 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

Stillwell.
 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
lymph nodes)
• 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
bacteria !!!!!!!!
• Over 500 species of bacteria
present in human colon.
• Lactobacillus,Bifidobacterium
and Acidophilus comprise the
majority of healthy bacteria in
the colon along with other
disease producing bacteria.
 Factors affecting the intestinal micro
ecosystem
• During infancy :
 Mother’s microbiology
 Mode of delivery
 Feeding practices

• Later in life :
Antibiotics and other drug intake
Microbial infections
Diet (highly processed, low fiber)
Chronic diarrhea
Stress
Chlorinated water
 Gut Flora in
Breast Fed vs Formula Fed Babies
 Dysbiosis
 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
cigarette smoking
 Nutraceuticals
 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
acids

– 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

 ‘‘Live microorganisms
which when administered
in adequate amounts
confer a health benefit on
the host’’
(WHO)
Why are Probiotics important for Human health?

Antibiotics Destroy the Problems in

gut micro flora digestion

Alcohol
consumption Problems in
Emergence of absorption of
antibiotic nutrients in the
resistant strains body

Stress

Probiotics
 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.

Contd….
 Key properties of probiotic
 Good adhesion/ colonization to human intestinal tract
and influence on gut mucosal permeability.

 Antagonistic against carcinogenic/ pathogenic

organisms.

 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
Lactobacillus species Bifidobacterium species
L. acidophilus B. bifidum
L. casei (rhamnosus) B. longum
L. reuteri B. breve
L. bulgaricus B. infantis
L. plantarum B. lactis
L. johnsonii B. adolescentis
L. lactis
Others
Bacillus cereus
Non pathogenic Escherichia coli
Saccharomyces cerevisiae (yeast)
Enterococcus faecalis
Streptococcus thermophilus
 Mechanism of action
 Bioconversion of, for example, sugars into fermentation
products

 Production of growth substrates, like vitamins B and K, for

other bacteria

 Direct antagonism by antimicrobial substances:

– hydrogen peroxide
– organic acids
– Bacteriocin
– acidophilin
 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

intestinal properties

 Stimulation of innate immune response

 PROBIOTICS

Normalise Metabolic
Immunomodulation
Intestine effects

Suppression of Production of
Strengthens
PPMs vitamins;
immunity
improves digestion

Intestinal Alleviate
mucosal integrity food allergy symptoms Lactose tolerance

Regulation of Lowers cholesterol

bowel movement Control of IBD (Bile acid deconjugation
IBS & Secretion)
 Foods containing Probiotics
• Milk
• Soya milk
• Tofu
• Milk products- Sour cream, Butter milk, Yoghurt
• Fermented Indian foods like
 Idlis
 Dosas, uttapam
 Dhoklas
 Vadas
 Kadhi
 Probiotic products marketed in
India
 India is an emerging market for probiotic
products, being the largest producer of
milk.
 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
“PREBIOTICS”
 Prebiotics
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."
 Prebiotics- examples
Garlic, Onions
Chicory root
Asparagus
Wheat
 Rye , Barley
breast milk
tomatoes, berries
bananas
 Established prebiotics
Name Obtained from/manufactured by
Extraction from chicory root, Wheat, banana, onions,
Inulin garlic, leek

Fructo-oligosaccharides Tranfructosylation from sucrose, or hydrolysis of chicory

inulin
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
mature milk
 Clinical application of probiotics and
prebiotics
Proven Benefits
• 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)

Suggested Benefits
• Food allergies

• Eczema
 Clinical application of probiotics and
prebiotics
Holds Promise
• Cystic fibrosis
• Allergic rhinitis
• Dyslipidemia/
• Asthma
Cardiovascular diseases
• Colic
• Rheumatoid arthritis
• Colon cancer prevention
• Traveller’s diarrhea /
• Obesity
bacterial enteritis
• Hypertension
• Genitourinary tract
• In elderly
infections
Probiotics in the Treatment of Gastrointestinal
Disorders
Diarrhea
Acute infectious
Antibiotic-associated
C. difficile H. pylori
Eradication

Lactose
IBD
Intolerance
Ulcerative colitis
Crohn’s disease
Pouchitis
Constipation
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

Probiotics
Disturbance of
intestinal microbiota

Microbiota Clostridium overgrowth

in balance produces toxin
 Lactose intolerance
 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
disorders.

 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
cells,
 to produce a high quantity of lactic acid, and
 to proliferate rapidly.
 Hypercholesterolemia

Lactic acid bacilli

Increases production of Increases bile

Short chain Fatty Acid
.
Bile syn. Increases
Inhibits cholesterol syn
by liver
More cholesterol is used up

Decreases blood chlesterol

Decreases cholesterol
 Probiotics and Cancer

Enzymes (Glycosidase, B- glucuronidase , azoreductase ,

and nitroreductase) of the intestinal flora convert the
precarcinogens to active carcinogens giving rise to
colon CA.

Probiotics reduce
 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
Prebiotics are defined as nonliving
non-digestible special form of fiber
or carbohydrates.
The powder form of prebiotics
can survive heat, cold, acid.
Prebiotics perform their role by
nourishing the bacteria that live
in the intestines.
Probiotics
Probiotics are referred to as live
active microorganisms that when
administered in adequate amount will
have beneficial effects to its host.
• more fragile.
• vulnerable to heat.
• may be killed over time.
Probiotics fight the harmful
bacterial species present in the
gut.
 Adverse effects
 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 patients.

 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
drugs.
 Are probiotics supplements
necessary?
 Probiotics supplements are not necessary for normal,
healthy individuals.

 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
intestines.
 Synbiotics
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
bacteria

• Activation of metabolism of beneficial bacteria,

antagonistic toward pathogenic bacteria
 Probiotic market
 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.
Source: http://www.bccresearch.com/market-research/food-
and-beverage/probiotics-market-fod035d.html
 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
piggery.

• 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
in India

Central Food Technology And Research Institute,

Mysore, India

National dairy research institute, Karnal, Haryana, India

• Institute of microbial technology, Chandigarh, India

• National dairy development board, Anand, Gujarat,

India

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.