PROBIOTICS
Dr. Devendra Jain
Assistant Professor & PI (AINP-SBB)
Department of Molecular Biology and Biotechnology
Maharana Pratap University of Agriculture and Technology
Udaipur (Rajasthan), India
devendrajain@mpuat.ac.in; devroshan@gmail.com ; +91-9929840357
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Maharana Partap University of Agriculture
and Technology,Udaipur,India
HISTORY OF PROBIOTICS- 1900’S
• 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”
3
UNDERSTANDING THE
DEFINITIONS
•
•
Prebiotic - (greek - before life) a substance (usually an
oligosaccharide) that cannot be digested but does
promote the growth of beneficial bacteria or probiotics
Probiotic - (for life) a substance that contains
microorganisms or bacteria that are beneficial to the
host organism.
• Symbiotic - (plus life) a substance containing both a
prebiotic and probiotic.
4
DEFINING A PROBIOTIC
• The term probiotic
comes from the Latin or
Gree pro, “before,
forward”, and bios, or
“life” — thus probiotics
are life-promoting. In
this case, we use the
term probiotics to refer
to beneficial bacteria
5
HISTORY OF PROBIOTICS
Bulgarian yoghurt (sour milk), commonly
consumed plain, is popular for its taste, aroma,
and quality. The qualities arise from the
Lactobacillus bulgaricus and Streptococcus
thermophilus culture strains used in Bulgaria
In 1907 Metchnikoff proposed that the acid producing
bacteria in fermented milk products could prevent
“fouling" in the large intestine and, if consumed
regularly, lead to a longer, healthier life.
6
HISTORY OF PROBIOTICS- 1930’S
In early 1930’s, in Japan, Minoru Shirota
developed a fermented milk product called
Yakult
In 1935 he started marketing Yakult as a
probiotic yogurt-like product made by
fermenting a mixture of skimmed milk with
a special strain of Lactobacillus casei shirota
7
HISTORY OF PROBIOTICS- 1965
• Probiotics term coined in 1965 by Lilly And
Stillwell
• Probiotics defined as microorganisms that have a
beneficial effect on the host intestinal microbial
balance
• Probiotics, which means “for life” was meant to
contrast “antibiotics”, popularly prescribed and
known to also destroy beneficial organisms and
impact the immune system.
8
PROBIOTICS IN INDIAN FOODS
• In ancient Indian
society, it became
commonplace (and still
is) to enjoy a beforedinner yogurt drink
called a lassi. These
Indian traditions were
based on the principle
of using sour milk as a
probiotic delivery
system to the body.
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CHARACTERISTICS OF EFFECTIVE PROBIOTICS
Probiotic microorganisms are:
• Able to survive the passage through the digestive system
• Able to attach to the intestinal epithelia and colonize
• Able to Maintain good viability
• Able to utilize the nutrients and substrates in a normal diet
• Non-pathogenic and non-toxic
• Capable of exerting a beneficial effect on the host
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WHAT ARE PROBIOTICS
• Probiotic organisms are live microorganisms
thought to be beneficial to the host organism.
According to the currently adopted definition by
FAO/WHO, probiotics are: "Live microorganisms
which when administered in adequate amounts
confer a health benefit on the host". Lactic acid
bacteria (LAB) and bifidobacteria are the most
common types of microbes used as probiotics;
but certain yeasts and bacilli may also be used.
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PROBIOTICS ARE PART OF THE
INTESTINAL TRACT
• Probiotics are bacteria that help maintain the natural
balance of organisms (microflora) in the intestines
camera. The normal human digestive tract contains
about 400 types of probiotic bacteria that reduce the
growth of harmful bacteria and promote a healthy
digestive system. The largest group of probiotic
bacteria in the intestine is lactic acid bacteria, of which
Lactobacillus acidophilus, found in yogurt with live
cultures, is the best known. Yeast is also a probiotic
substance. Probiotics are also available as dietary
supplements
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Probiotic Food 1:
Natto
Fermented
soybeans
from Japan
High in protein,
vitamin K &
nattokinase
(enzyme)
Spicy pickled
cabbage
from Korea
High in vitamin A,
C, B1, B2, betacarotene, calcium,
iron, enzymes &
lactobacillus
kimchii (bacteria)
Probiotic Food 2:
Kimchi
Probiotic Food 3:
Miso
Soybean
paste from
Japan
High in
protein,
vitamin B12
& trace levels
of minerals
Probiotic Food 4:
Tempeh
Soybean cake
from
Indonesia
High in fiber,
protein &
Rhizopus
oligosporus
(bacteria)
Probiotic Food 5:
Sauerkraut
Pickled
cabbage
from Europe
High in vitamin C,
digestive
enzymes & lactic
acid bacteria
Probiotic Food 6:
Kefir
Fermented
milk from
from Europe
High in
protein &
lactic acid
bacteria
+
Lactobacillus bulgaricus
Activia®, a probiotic yogurt (Danone)
+
Streptococcus thermophilus
Bifidobacterium animalis
DN-173 010
+
Lactobacillus bulgaricus
+
Streptococcus thermophilus
Activia®, a probiotic drink (Danone)
Lactobacillus casei DN-114 001
PREBIOTICS DIFFERS FROM
PROBIOTICS
• A prebiotic is a nondigestible component
which beneficially affects the host by
selectively stimulating the growth and/or
activity of one or a limited number of
colonic bacteria, thereby improving the
health of the host , prebiotics are
nutrients that the bacteria use as a
fuel source; these include dietary fiber
and carbohydrates
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PREBIOTICS
• A prebiotic is a nondigestible component which
beneficially affects the host by selectively stimulating
the growth and/or activity of one or a limited number of
colonic bacteria, thereby improving the health of the
host
***In other words, prebiotics are nutrients that the
bacteria use as a fuel source; these include dietary
fiber and carbohydrates
PREBIOTICS- 3 CRITERIA
• Must not be hydrolyzed nor absorbed in the upper
gastrointestinal tract
•
Must be a substrate for growth or activity of one or a
limited number of beneficial colonic bacteria
• Must therefore be able to alter the colonic microflora
towards a healthier composition and to induce
luminal or systemic effects which are beneficial to the
health of the host
PREBIOTICS- EXAMPLES
• Inulin
• Garlic
• Onions
• Chicory root
• Asparagus
• Whole wheat
• Rye
• Barley
Potential Benefits
Lactose Intolerance: lactose to lactic acid
Prevention of Colon Cancer: LAB ability to bind with heterocyclic amines, which
are carcinogenic substances formed in cooked meat
Cholesterol Lowering
Lowering Blood Pressure: due to the ACE (Angiotensin-Converting Enzyme)
inhibitor-like peptides produced during fermentation
Improving Immune Function and Preventing Infections: improve immune
function by increasing the number of IgA-producing plasma cells, increasing or
improving phagocytosis as well as increasing the proportion of T lymphocytes and
Natural Killer cells
Helicobacter pylori and Antibiotic-associated diarrhea
Diarrhea: treat various forms of gastroenteritis. They might reduce both the
duration of illness and the frequency of stools. Fermented milk products (such as
yogurt) also reduce the duration of symptoms.
Reducing Inflammation: modulate inflammatory and hypersensitivity responses, due
to the regulation of cytokine function
Improving Mineral Absorption: correct malabsorption of trace minerals
Prevents Harmful Bacterial Growth Under Stress
Irritable Bowel Syndrome (IBS) and Colitis
symptom-based diagnosis characterized by chronic abdominal pain, discomfort,
bloating, and alteration of bowel habits. As a functional bowel disorder, IBS has no
known organic cause.
Onset of IBS is more likely to occur after an infection (post-infectious, IBS-PI), a
stressful life event, or onset of maturity.
The most common theory is that IBS is a disorder of the interaction between the
brain and the gastrointestinal tract, although there may also be abnormalities in the
gut flora or the immune system.
Antibiotic-associated diarrhea (AAD) results from an imbalance in the colonic
microbiota caused by antibiotic therapy.
Microbiota alteration changes carbohydrate metabolism with decreased short-chain
fatty acid absorption and an osmotic diarrhea as a result. Another consequence of
antibiotic therapy leading to diarrhea is overgrowth of potentially pathogenic
organisms such as Clostridium difficile. Probiotic treatment might reduce the
incidence and severity of AAD as indicated in several meta-analyses.
For example, treatment with probiotic formulations including Lactobacillus
rhamnosus may reduce the risk of antibiotic-associated diarrhea, improve stool
consistency during antibiotic therapy
Probiotics
Super infection: is a condition produced by sudden growth of a type of
bacteria different from the original offenders in a wound or lesion under treatment,
such as Clostridium difficile overgrowth post antibiotic treatment.
A classic example of a superinfection resulting from antibiotic administration is the
disease pseudomembranous enterocolitis caused by Clostridium difficile.
When a patient is treated with clindamycin, ampicillin, or cephalosporin, many
intestinal bacteria are killed, but C. difficile is not.
This intestinal inhabitant, which is normally a minor constituent of the population,
flourishes in the absence of competition and produces a toxin that stimulates the
secretion of a pseudomembrane by intestinal cells.
If the superinfection is not treated early with vancomycin, the pseudomembrane
must be surgically removed or the patient will die.
Fungi, such as the yeast Candida albicans, also produce superinfections when
bacterial competition is eliminated by antibiotics.
PROBIOTICS AND CANCER
• Enzymes (Glycosidase, B- glucuronidase , azoreductase ,
and nitroreductase ) of the intestinal flora convert the
precarcinogens to active carcinogens
•



Probiotics reduce:
Faecal concentrations of enzymes
Secondary bile salts
Reduce absorption of harmful mutagens that may
contribute to colon carcinogenesis.
• Activity of L. acidophilus and L. casei supplementation
in humans helped to decrease levels of these enzymes
• Several mechanisms have been proposed as to how
lactic acid bacteria may inhibit colon cancer:
 Enhancing the host’s immune response
 Altering the metabolic activity of the intestinal
microflora
 Binding and degrading carcinogens
 Producing antimutagenic compounds
 Altering the physiochemical conditions in the colon
(Harish and Varghese, 2006)
HEPATIC DISEASES
Mechanisms by which probiotics may treat Hepatic
Encephalopathy:
• Decreased portal blood ammonia by reduced bacterial
urease activity
• Decreased pH due to less ammonia absorption
• Less intestinal permeability and improved gut epithelium
•
Decreased inflammation and oxidative stress due to
reduced ammonia toxins
• Reduced uptake of other toxins
HELICOBACTER PYLORI INFECTIONS
•
It the most common chronic bacterial infection in humans and causes :
 Chronic gastritis
 Peptic ulcers
 Gastric adenocarcinoma
 Lymphoma and a number of non-gastrointestinal disorders.
• In vitro studies have suggested that lactic acid bacteria may inhibit or
kill H. pylori by acting as a bactericide .
• Bifidobacteria and B. subtilis may inhibit the growth or attachment of
H. pylori.
• Possible mechanisms by which L. salivarius eradicates H. pylori include
the ability of the former to bind to gastric epithelial cells, to produce a
high quantity of lactic acid, and to proliferate rapidly.
USE OF PROBIOTICS BEYOND GIT
• Allergy: Probiotics have the potential:
 To modify the structure of antigens
 Reduce their immunogenicity
 Reduce intestinal permeability
 Generation of proinflammatory cytokines that are
elevated in patients with a variety of allergic
disorders
Probiotics in Pregnancy:
• Bacterial vaginosis , increases the risk of preterm labour
and infant mortality .
• Probiotics decrease the risk of bacterial vaginosis and
maintain normal lactobacilli vaginal flora
• Studies using L. rhamnosus GG and B. lactis BB12 have
shown that atopic dermatitis, a condition that causes
severe skin rashes in up to 15% of babies, can be
prevented in 50% of cases if mothers ingest probiotics
during pregnancy and newborns ingest them during the
first 6 months of life
USE OF PROBIOTICS
• All probiotics works effectively, if taken after meals, when
stomach acid is lowest.
• Stomach acid destroys up to 99.9% of probiotics, if taken
before a meal but only about 90%, if taken after meal.
• Thus, after meal intake ensures maximum delivery to the
small intestine, where they reproduce rapidly, populating
the colon.
• They do most of their good work in the small and large
intestines, but they also help the mouth and esophagus to
remain uninfected.
POSSIBLE MODES OF ACTION OF PROBIOTICS
 production of inhibitory compounds
 competition for chemicals/available energy
 competition for adhesion sites (exclusion)
 enhancement of the immune response
 improvement of water quality
 interaction with phytoplankton
 a source of macro- and micro-nutrients
 enzymatic contribution to digestion
Most commonly used Probiotics are lactic acid bacteria Lactobacilli, Streptococci and Bifidobacteria
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PROBIOTIC MICROORGANISMS
AND MODE OF ACTION
Most commonly used Probiotics are lactic acid
bacteria - Lactobacilli, Streptococci and
Bifidobacteria
Possible modes of Action:
•
•
•
•
Competitive exclusion
Production of Bacteriocins
Production of organic acids
Altered absorption of the intestinal mucosa
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PROBIOTIC PRODUCTS - WHY DO THEY
MATTER?
 80% of our immune system is located in the digestive tract
 Probiotics play a fundamental role in human health
 Losing the balance
- Fast paced lifestyle
- Food
- Stress
- Alcohol/ Cigerettes
- Illness
- Antibotic medications
- Age
Representation of functions and health benefits of probiotics
ADVANTAGES
• Produce lactic acid- lowers the pH of intestines and inhibiting bacterial
villains such as Clostridium, Salmonella, Shigella, E. coli, etc.
• Decreases the production of a variety of toxic or carcinogenic metabolites.
• Aid absorption of minerals, especially calcium, due to increased intestinal
acidity.
•
Production of β- D- galactosidase enzymes that break down lactose.
•
Produce a wide range of antimicrobial substances -acidophilin and
bacteriocin etc. help to control pathogenic bacteria .
•
Produce vitamins (especially Vitamin B and vitamin K)
•
Act as barriers to prevent harmful bacteria from colonizing the intestines
Colon cancer – Certain probiotics (Lactobacillus bulcaricus) may help prevent
colon cancer by preventing the
breakdown of enzymes (βglucuronidase) that contribute to the growth of cancer causing agents.
Lowering cholesterol - a range of LAB able to break down
bile in the gut, thus inhibiting its reabsorption (which enters
the blood as cholesterol)
Blood pressure reduction -Consumption of milk fermented with various
strains of LAB may result in modest reductions in blood pressure, due to the ACE
inhibition-like peptides produced during fermentation.
•
Treat allergy –
1.
Degradation/structural modification of enteral antigens.
2.
Normalization of the properties of aberrant indigenous microbiota and of
gut barrier functions.
3.
Regulation of the secretion of inflammatory mediators, and promoting
development of the immune system.
4.
Prevents food allergy by promoting endogenous barrier mechanisms and
alleviating intestinal inflammation.
5.
Stimulating immune response and reduction of serum IgE levels.
6.
Reduction of Th2 cytokine response.
IDENTIFICATION OF STRAINS OF
PROBIOTICS
• Effects of probiotics are strain specific. Strain identity is
important to link a strain to a specific health effect as
well as to enable accurate surveillance and
epidemiological studies. Both phenotypic and genotypic
tests should be done using validated standard
methodology. Nomenclature of the bacteria must
conform to the current, scientifically recognized names
as per the International Committee on Systematics of
Prokaryotes (ICPS) (available at http://www.theicsp.org/)
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PROBIOTICS USE – IS IT SAFE ???
• Most probiotics are like what is
already in a person's digestive
system. Some probiotics have
been used for a very long time
throughout history, such as in
fermented foods and cultured
milk products. These don't
appear to cause illness. But
more study is needed on the
safety of probiotics in young
children, the elderly, and people
who have weak immune
systems.
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SIDE EFFECTS OF PROBIOTICS
• Rare cases cause bloating, diarrhea, abdominal pain.
• If in excess cause infection that require medical attentions.
• People having on underlying disease or compromised immune system
cause potential health problems like skin rash, fever, bloody stools etc.
• Sometimes interact with immunosupressive drugs leading to life threating
cnditions. So people taking such drugs should avoid it.
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 (Gibson, 2004).
 Potential synergy between pro- & prebiotics
 Improve survival in upper GIT
 More efficient implantation
 Stimulating effect of Probiotics
SOME OF THE MAJOR 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
• Production of antimicrobial substances (bacteriocins , hydrogen
peroxide, organic acids etc)
•
Immunostimulation
• Anti-inflammatory, Anti-mutagenic, Anti-carcinogenic, and production
of bioactive compounds (enzymes, vaccines, peptides etc)
(Nagpal et al, 2007)
PRODUCTS IN THE INTERNATIONAL MARKET
USING SYNBIOTIC HEALTH FOODS CONCEPT.
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Product
Actifit
Probioplus
Symbalance
Proghurt
Fysiq
Vifit
Fyos
“On Guard” (Liquid yoghurt)
Impact
Orafti’s synergy- 1
Synbiotic supplement
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Producer
Emmi, Switzerland
Migros, Switzerland
Tonilait, Switzerland
Ja naturlich naturprodukte, Austria
Mona, Netherlands
Sudmilch / Stassano, Belgium,
Germany, UK
• Nutricia, Belgium
• LBL Foods, US
• National Cancer Institute, USA
ADMINISTRATION OF PROBIOTICS
• “The specific microorganisms shall be viable, active &
abundant at the level of at least 10 7 cfu /g in the product to
the date of minimum durability”
• Minimum Consumption: 100g of a probiotic food with
107 cfu/ g.
PROBIOTIC RESEARCH
• Allergies - certain probiotics have an impact on the
mucosal barrier function of the intestinal tract. This
effects allergens entering the body and the activity of
inflammation producing cells
• Cholesterol – regular consumption of certain
probiotic dairy products may have an impact on
cholesterol level and may affect the levels of “good”
HDL in the blood
• Colon Cancer – Certain probiotics may help prevent
colon cancer by preventing the breakdown of
enzymes that contribute to the growth of cancer
causing agents
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PROBIOTIC RESEARCH
• Infant Health – Mother nature has long recognized the
benefits of Probiotics. Human breast milk contains a
protein that stimulates the growth of good bacteria to help
with digestion. Therefore a way to create and maintain a
perfect balance of gut bacteria in babies has been in
existence for as long as babies have been born
• Probiotics in Infant Formulas with the added protective
benefit of beneficial probiotic cultures like those naturally
promoted by breast milk, help support Baby’s healthy
immune system. High levels of Bifidobacteria in the
digestive tract are thought to be one of the reasons why
breastfed babies are generally so healthy
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PROBIOTIC RESEARCH
Continued clinical research to study the benefits of
probiotics in the areas of :
• Obesity and Weight Management (exopolysaccharide
producing probiotic strains)
• Prevention of osteoporosis (improved bioavailability
and absorption of nutrients)
• Growth development in children (improved
bioavailability and absorption of nutrients)
• Treating and preventing respiratory infections,
specially in children (boost immune system)
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PROBIOTIC RESEARCH
• Acne treatment and clearer skin (maintaining a healthy
balance of beneficial intestinal micro flora)
• Cancer control (bind, block or remove carcinogens,
activate the host’s immune system to antitumor
genesis, inhibit bacteria that directly or indirectly
convert procarcinogens to carcinogens)
• Animal health (boost immune system, maintain balance
of intestinal microflora)
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RESEARCH ON CANCER
STILL EXPERIMENTAL
• The strongest evidence for
the anti-cancer effects of
probiotics comes from
animal studies; evidence
from human studies
(epidemiology and
experimental) is still limited.
An important goal for the
future should be carefully
designed human clinical
trials to corroborate the
wealth of experimental
studies.
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THANK YOU