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PROBIOTICS AND

PREBIOTICS
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 :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)

 A Probiotic is proven to
survive the passage through
the the passage through the
gastro-intestinal tract.
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
L.monocytogenes (FNCC 0156) S.aureus (FNCC 0047) E.coli (FNCC 0091)

D44a D44b D44c

The inhibitory effect of bacteriocins were also observed by the formation


of clear zone around agar wells
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


Administration of probiotics

• “The specific microorganisms shall be viable, active &


abundant at the level of at least 107 cfu /g in the product to
the date of minimum durability”
• Minimum Consumption: 100g of a probiotic food with 107
cfu/ g.
Strains of bacteria one should look for in a probiotic:

• It is important to choose a high quality formula that contains


the right strains of bacteria for optimum results .
• It is best to choose a probiotic that contains the entire family
of lactobacillus bacteria.
• The family members are : L. acidophilus, L. delbrueckii, L.
casei, L. bulgaricus, L. caucasicus, L. fermenti, L. plantarum,
L. brevis, L. helveticus, L. leichmannii, L. lactis, L. bifidus,
and L.sporogenes.
• It is important that the complete family of 13 strains is
present. Most people don’t realize this family works in
harmony only if the complete family is present.
• A good probiotic should have most of these strains:
• Bifidobacterium bifidum - Protects the body against
invasive pathogens, salmonella and rotavirus. Helps
suppress tumors and reduce inflammation. Helps
protect against diarrhea and intestinal infections and
strengthens immune system.
• Bifidobacterium breve - Helps prevent rotavirus-induced
diarrhea and activates your immune system. Also helps
IBS.
• Bifidobacteria infantis - Inhibitory effect on some strains of
E. coli. Protects against gastroenteritis (inflammation of
the stomach and bowels) and is useful in the prevention
and therapy of solid tumors (breast tumors).
• Bifidobacteria lactis - Enhances resistance to oral
salmonella typhimurium. Enhances natural immune
function. Helps alleviate constipation, prevents diarrhea
and decreases chronic inflammation of the colon.
• Bifidobacterium longum - Able to eliminate harmful
nitrates commonly found in foods. Inhibits the
development and growth of colon, liver and breast
cancers in laboratory animals. Helps prevent diarrhea
caused by antibiotic use, helps constipation and reduces
fecal odor.
• Lactococcus lactis - A natural antibiotic that reduces the
ability of pathogenic microbes to grow and cause
infection.
• Lactobacillus salivarius - Produces a high amount of
lactic acid, thus completely inhibiting the growth of
Helicobacter pylori (H. pylori) bacteria, which are now
known to be the major cause of peptic ulcers. It is also
effective against Salmonella typhimurium
• Lactobacillus casei- Provides protective activity against Listeria
bacteria which have been found to cause the inflammation and
infection of the brain and spinal cord (Spinal Meningitis).
Inhibits activity in tumor cells and stimulates beneficial
activity in normal cells.
• Lactobacillus reuteri - Controls Cryptosporidium parvum (C.
Parvum), a parasite that survives the chlorination process,
sometimes found in springs or water wells, infection causing
nausea, diarrhea, fever and abdominal cramps. Beneficial in
the treatment of diarrhea associated with rotavirus, E. coli and
Salmonella.
• Lactobacillus sporogenes – Can reduce LDL (harmful)
cholesterol levels, while increasing HDL (healthy).
• Streptococcus thermophilus -Its antioxidant activity scavenges
the body for free radicals. Effective in maintaining vaginal and
intestinal health.
Foods containing Probiotics
• Milk
• Soya milk
• Tofu
• Milk products- Sour cream, Butter milk, Yoghurt
• Fermented Indonesian foods like
 Dadih
 Urutan
 Tempoyak
Probiotic products marketed in
Indonesia
 Indonesia an emerging market for
probiotic products, being the largest
producer of milk.
 Yakult , Acitivia, Cimory, Yogurt
Streptococcus faecalis T-110 30 million
Clostridium butyricum TO-A 2 million
Bacillus mesentericus TO-A 1 million
Lactobacillus sporogenes 50 million
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."
• Human could consume nearly 10 g of non-digestible
fermentable carbohydrates without noticeable side
effects and recommended a dose of 5 to 8 g of
oligofructose and 10 g of inulin per person.
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
Concept of Probiotics and Prebiotics:

Harish and Varghese, 2006


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.
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
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.
Japanese probiotic milk-like product made
by fermenting a mixture of skimmed milk
with a special strain of the bacteria
Lactobacillus casei Shirota.

By Minoru Shirota in 1930

Standard Yakult (excludes variations such as in Yakult


Light) contains :

Sugar (sucrose) to balance sourness with sweetness.


Skim milk powder
Dextrose
Natural flavours
Live Lactobacillus casei strain Shirota , 6.5 billions per
65 mL bottle (concentration of 108 CFU/mL)
Water
Prebiotics vs Probiotics
Prebiotics Probiotics
Prebiotics are defined as nonliving Probiotics are referred to as live
non-digestible special form of fiber active microorganisms that when
or carbohydrates. administered in adequate amount will
have beneficial effects to its host.

The powder form of prebiotics • more fragile.


can survive heat, cold, acid. • vulnerable to heat.
• may be killed over time.

Prebiotics perform their role by Probiotics fight the harmful


nourishing the bacteria that live bacterial species present in the
in the intestines. 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

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