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Probiotics, Prebiotics:
Emerging importance in
Pharmacology
Overview of Presentation
• Introduction
• History
• Facts about intestine
• Probiotics
• Definition
• Criteria
• Mechanism of action
• Safety issues
• Assosiated benefits
• Drug interactions
• Precautions &
contraindications
• Prebiotics
• Definition
• Criteria
• Mechanism of action
• Potential benefits
• Assosiated risks
• Clinical applications
• Regulatory guidelines
• Challenges
• Postbiotics, synbiotics etc.
• Conclusion
Introduction
• Quality healthcare is the foundation of any prosperous nation.
• Long before the existence of microorganisms was known or recognized,
fermented products were used therapeutically, to treat colds, fevers, and
ailments of the gastro intestinal tract such as constipation and diarrhea.
• Research has shown that Probiotics and Prebiotics are useful in achieving
positive health effects and well being to the host.
• It however gained momentum only recently.
• India is also fast emerging as a potential market for these.
• Probiotic product industries in India were estimated to be around Rs 20.6
million with a projected annual growth rate of 22.6% until 2015
Intestine is a paradise of disease
“Death sits in the bowels; a bad digestion is the root
of all evil” - Hippocrates, ca. 400 BC
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
hypothesised that consuming large amounts of fermented
milk products that contained Lactobacillus bacteria (“soured
milk”) could prolong and improve the quality of life.
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 in 1954 to indicate substances that were
required for a healthy life
• Probiotics term coined in 1965 by Lilly And Stillwell
• Japanese were the first to recognise the value of non-digestible
oligosaccharides
• It was not until 1995 that the scientific concept for human gut microbiota
modulation by “prebiotics” was introduced
• 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, Payer’s patches and
mesenteric lymph nodes)
• Our Intestine = 400 square meter surface…
i.e. the surface area of a tennis court
Largest immune organ
• 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, Bifidis and
Acidophilus comprise the
majority of healthy bacteria
in the colon along with other
disease producing bacteria.
• Normal ratio is 4:1.
Facts about Intestine
• Dysbiosis is the abnormal microbial colonization of the
intestine , where changes in quantity and quality of flora
become pathological & harmful.
• Common cause of dysbiosis:
• Antibiotic therapy
• Others are fast paced lifestyle, stress, food habits, chlorine in drinking
water, Alcohol intake and cigarrete smoking
• Age
• Autoimmune conditions (rheumatoid), IBD etc.
Dysbiosis
Terminologies
• Prebiotics (before life)- A substance that cannot be digested but
thus promote the growth of beneficial bacteria and probiotics.
• Probiotics (for life)- live microorganisms which when
administered in adequate amounts confer a health benefit on the
host.
• Synbiotics (plus life)- substance containing both above.
• Antibiotics (against life)-A substance that can destroy or
inhibit the growth of other microorganisms. Antibiotics are
widely used in the prevention and treatment of infectious
diseases.
Terminology
• Biotherapeutic agent: A therapeutic material produced
using biological means, including recombinant DNA
technology eg. interferons, interleukins, and growth factors
• Functional foods- defined as products that are similar in
appearance to conventional foods that are consumed as
part of a normal diet and have demonstrated physiological
benefits, and/or have the potential to reduce the risk of
chronic disease beyond nutritive function, i.e. they contain
bioactive compounds.
• 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 :- Engineered grain, cereals supplemented with
vitamins or minerals, genetically manipulated soybean and
canola oil without trans-fatty acids
Nutraceuticals
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
Probiotics
Definition
• Probiotics - live microorganisms which, when
administered in adequate amounts, confer a
health benefit on the host ( FAO/WHO 2001)
Characteristics of Effective Probiotics
Probiotic microorganisms should be:
• Able to Maintain good viability
• Able to survive the passage through the digestive system
• Must not deconjugate bile salts
• Able to attach to the intestinal epithelia and colonize
• Carry no antibiotic resistance genes that can be transferred to pathogens
• Able to utilize the nutrients and substrates in a normal diet
• Capable of exerting a beneficial effect on the host
• Produce Antimicrobial Compound
• Organic acids
• Hydrogen peroxide
• Carbon dioxide
• Diacetyl
• Acetaldehyde
• Bacteriocins
• To be safe, noninvasive, noncarcinogenic and
nonpathogenic
• Coaggregate to form a normal balanced flora
• Strain must not induce an immune reaction in the host
Levels of action
Mechanism of action
(1) Competition for dietary ingredients as growth substrates,
(2) Bioconversion of, for example, sugars into fermentation products
(3) Production of growth substrates, for example vitamins, for other
bacteria
(4) Direct antagonism by bacteriocins
(5) Competitive exclusion for binding sites
(6) Improved barrier function
(7) Reduction of inflammation, thus altering intestinal properties
(8) stimulation of innate immune response (by unknown mechanisms)
Beneficial effects of probiotics
• Immunological benefits-
• Activate local macrophages to increase antigen
presentation to B lymphocytes and increase IgA
production locally
• Modulate cytokine profile
• Induce hyporesponsiveness to food allergies
• Lower blood ammonia levels
• Lower serum cholesterol levels
• Produce vitamins eg: vitamin B,K, folic acid
• Promote normalization of intestinal flora after antibiotic
therapy
• Act as immunomodulator- by promoting attacks on
malignant cells
• Nonimmunologic benefits-
• Digest food and compete for nutrients with
pathogens
• Alter local pH
• Produce bacteriocin to inhibit pathogen
• Scavange superoxide radical
• Stimulate epithelial mucin production
• Enhance intestinal barrier function
• Compete for adhesion with pathogen
• Modify pathogen derived toxins
Forms and Dosage of probiotics
• Most common forms for probiotics are dairy
products and probiotic-fortified foods
• Formulations: drops, chewable tablets,
lozenges, capsules, straws, bottle caps and
bacteria in freeze-dried form are also available
• Sporolac, ViBact, Darolac, Biglac, Bifilac etc.
• Dose needed depending on the strain and
product.
• Over the counter dose is 1-10 billion cfu/dose
• Bifidobacterium infantis for IBS-100 million cfu/dose
• Dose-Varies greatly with product
• Live and active cultureYogurts must contain >108
[100 million]
• L.rhamnosus GG has 10 billion
• Duration: probiotics are taken daily for 2weeks to
2 months
• Often taken empty stomach
• If taken along with antibiotics, gap of 2 hrs.
Fecal microbiota transplantation
(FMT)
• FMT is the process of transplantation of fecal bacteria from a healthy
individual into a recipient patient for the treatment of C. difficile
infection.
• The procedure can be carried out via enema (simplest and most
acceptable) through the colonoscope, or through a nasogastric or
nasoduodenal tube.
• Most patients with C. difficile infection recover and have it eradicated
after just one treatment.
Established Probiotics
• The majority of probiotics are incorporated into dairy products such as milk powders,
yoghurt, cheese and ice cream
• Non-dairy products such as malt-based beverages and fruit juices meat sausages,
capsules, and freeze-dried preparations.
• Most common micro-organisms which are used:-
BIFIDOBACTERIUM
• Infantis (breastmilk)
• lactis
• longum
• breve
• Bifidum
LACTOBACILLUS(first and largest group)
• reuteri
• casei
• ramnosus
• Acidophilus
LACTOCOCCUS, SACCHAROMYCES, STREPTOCOCCUS,THERMOPHILUS, ENTEROCOCCUS
Drug Interactions
• Concurrent administration of antibiotics could kill a large number of
the organisms, reducing the efficacy of the Lactobacillus and
Bifidobacterium species. Patients should be instructed to separate
administration of antibiotics from these bacteria-derived probiotics
by at least two hours.
• S. boulardii might interact with antifungals, reducing the efficacy of
this probiotic
Precautions and Contraindications
• Critically ill or severely immunocompromised patients, probiotic
strains of Lactobacillus have been reported to cause bacteraemia,
endocarditis, meningitis.
• Short-bowel syndrome can have bacteremia, possibly due to altered
gut integrity.
• Caution is also taken in patients with central venous catheters.
• Lactobacillus preparations are contraindicated in persons with a
hypersensitivity to lactose or milk.
• S. boulardii is contraindicated in patients with a yeast allergy.
• No contraindications are listed for bifidobacteria, since most species
are considered nonpathogenic and nontoxigenic.
Prebiotics
Definition
• Prebiotics are defined as nondigestible food ingredients
(oligosaccarides) that are resistant to digestion and absorption , are
fermented by cecal /colonic microbiota, and selectively stimulate growth
and/or activity of bacteria that contribute to colonic and host health
• Prebiotics; are simply speaking the preferential “FOOD” for Friendly
Beneficial Bacteria colonizing the digestive tract.
• They are dietary supplements that play a role in Balancing the Intestinal
Mucosal Immune System
Colonic food
Criteria for eligibility as
prebiotics
1. Resistance to gastric acidity, to hydrolysis by
mammalian enzymes, and to gastrointestinal
absorption
2. Selective stimulation of the growth and/or activity of
intestinal bacteria that contribute to health and well-
being
3. Fermentation by intestinal microflora; to produce
SCFA & gas.
4. Induce LUMINAL or SYSTEMIC beneficial effects.
Gibson et al., 2007
Established prebiotics
Name Obtained from/manufactured by
Inulin Extraction from chicory root, Wheat, banana, onions,
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 Original they represent the third largest
component of Human Milk 20 - 23 gm/l in colostrum & 12- 14 gm/ in
mature milk
Aliment Pharmacol Ther 24, 701–714
Potential prebiotics
• Mannanoligosaccharides (yeast
cell wall)
• Glucooligosaccharides
• Lactose
• Arabinogalactan (radishes, carrots,
tomatoes and wheat)
• Polydextrose
• Glucuronic acid
• Sugar alcohols
• Pectin oligosaccharides (apple
pectin, citrus pectin)
• Whole grains
• gum arabic, guar gum
• Potential applications for prebiotics as food ingredients to improve the
gastrointestinal health include beverages, bakery products, table
spreads, sauces, infant formulae and weaning foods, cereals,
confectionery, snack bars, soups, salad dressings and dairy products
Mechanism of action
• Mechanisms by which prebiotics provide health
benefits
• Increases the amount of lactic acid producing
bacteria (lactobacilli and bifidobacteria)
• Increases the amount of Short Chain Fatty Acids
(SCFAs)- Butyrate, Acetate, Lactate etc…
• Activates carbohydrate receptor immune cells
Journal of Family Ecology and Consumer Sciences, Vol 35, 2007
Potential benefits
1. Fermentation of oligofructose in the colon results in a large
number of physiologic effects
• Increase mineral absorption( as they do not bind them)
• Shortening gastrointestinal transit time
• lowering blood lipid levels (decrease requirement of fat in
food because of their gel like property)
• Increasing fecal weight (decreases constipation)
• The increase in colonic bifidobacteria has been assumed to
benefit human health by
• producing compounds to inhibit potential pathogens
• reducing blood ammonia levels
• producing vitamins and digestive enzymes.
2. Production of short chain fatty acids (SCFA) eg: Acetate,
Propionate, and Butyrate and Lactic acid
• Increase water and sodium absorption
• Increase mucosal blood flow and mucosal cell proliferation hence
mucus production
• Improvement of the epithelial barrier function (by regulating tight
junction protein genes)
• Promoting homeostatic immunoregulation by the induction of
interleukin (IL)-10, transforming growth factor (TGF)-b and by the
inhibition of tumor necrosis factor (TNF)-a and IL-12 synthesis
• Prevent colon inflammation
• Decrease lymphocyte proliferation
• Inhibit C.K production
• Induce T lymphocyte apoptosis
• Activates G-Protein coupled receptors (supply fuel to immune cells)
Associated risks
• Fructose malabsorption (with FOS & Inulin)
• Can irritate GIT if taken in high dose and Ca+2
content is low (produced lactic acid irritates wall
of intestine)
• GI Disturbances:
• Constipation/ Diarrhoea
• Abdominal pain
• Flatulence
• Bloating
This is advantageous as it allows a relatively
broad “therapeutic window”
Forms and dosage
• Ispaghula husk as a loose powder. A good dose is 10 grams (= 2 heaped
teaspoons) twice daily. For IBS
• FOS (fructooligosaccharides) loose powder. A good dose is 2.5 grams (= 1
level teaspoon) twice daily.
• Inulin powder/syrups 2.5 grams (= 1 level teaspoon) twice daily (better
prebiotic than FOS)
• GOS (Galactooligosaccharides) 5 grams daily.
• Butyric acid capsules- Provide most of the benefits of probiotics, without
actually taking probiotics for upset of gut
• Start with lower doses for a few days, otherwise may experienced some
constipation.
• Caution is taken with antibacterial herbs or supplements that are taken
alongwith, which may inhibit the good bacteria as well as the bad.
The Wonders of Prebiotic.Hip, Oct 6, 2010.
Clinical application of probiotics and
prebiotics
Proven Benefit
• Diarrheal Illness (viral) - treatment and prevention
• Prevention of antibiotic-associated diarrhea
• Constipation
Suggested Benefit
• Food allergies
• Inflammatory bowel disease
• Lactose intolerance
• Treatment of recurrent Clostridium dificile infection (Clostridium dificile is a bacteria
that can cause serious infection in the intestine).
• Eczema
Holds Promise
• Cystic fibrosis
• Dyslipidemia/ Cardiovascular
dieases
• Liver disease
• Rheumatoid arthritis
• Traveler’s diarrhea / bacterial
enteritis
• Vaccine immuno-augmentation
• Genitourinary tract infections
• Necrotising enterocolitis
• Allergic rhinitis
• Asthma
• Attention deficit disorder (ADD)
/ Attention deficit hyperactivity
disorder (ADHD)
• Autism
• Colic
• Colon cancer prevention
• Obesity
Treating Infection
Antibiotic Associated Diarrhea
• Associated with C.difficile which may cause pseudomembraneous
colitis
• Lactobacillus GG successful in eradicating C.difficile
• Saccharomyces boulardii in DBC study reduced recurrence from
22% to 9.5%
• Useful in reducing the severity and duration of acute infectious
diarrhea in children
• Probiotics used in prevention and as adjuvant therapy in AAD.
Guandalini. J Clin Gastroenterol, 2008
Childhood diarrhea
• Metanalysis revealed length of course of childhood diarrhea
reduced 1–1.5 d, decreased frequency of infections, decreased
shedding of rotaviruses or promotion of systemic or local
immune response, increase in the production of rotavirus-specific
antibodies when probiotic added to treatment
• Probiotics given as suspended in oral rehydration solutions
• By stimulating rotavirus specific IgA production of through B
cells
Traveller’s diarrhea
• Incidence reduced from 71 to 43% in tourist study with S.boulardii
Floch. JClinGastro 2005;40:275
Allergy
• Atopic eczema, Dermatitis, Allergic rhinitis, Asthma, food allergies with
milk, eggs, peanuts, tree nuts, soy, wheat gluten, fish, shellfish and shrimp
• Atopic children tend to have a degree of dysbiosis, with more clostridia
and fewer bifidobacteria
•  IgE thought to be caused by a skewed balance between Th1 and T
helper type 2 cells
• Probiotics improving the Th1/Th2 balance in favour of a predominance of
Th1 cells
• Lactobacillus GG has been used to treat cow milk allergy and atopic
eczema
• prebiotic-supplemented infant formula reduce susceptibility to atopy but
that the benefits persist up to 2 years of age
Genitourinary
• Recurrent Candida Vaginitis and Bacterial Vaginosis have been
successfully treated by administration of both oral and vaginal
Lactobacilli
• Vaginal suppositories with 1 billion cfu
• Recent study in 185 Nigerian woman with vaginosis –
L.rhamnosus + L.reuteri + metronidazole more effective than
metronidazole alone – 88% to 40%*
Floch. JClinGastro 2005;40:275
IBD
• IBD is associated with a breakdown of the normal barrier function
provided by the gut epithelial lining and its associated mucus
commensal bacteria might be altered.
• Use of probiotics and prebiotics giving good results in
maintaining remission in UC but not of much in CD
• Usually 1x109, or 1 billion colony forming units (CFU) is a good
daily dose
IBS
• Prebiotics relieve constipating symptoms-
• Increased bacterial mass and osmotic water-binding capacity making
stools bulky
• Increased stool frequency and softer stools
• Butyrate, have a positive effect on the endothelium and on peristalsis,
which improves transit
• A reduction in abdominal bloating and flatulence as a result of
probiotic treatments is a consistent finding
• some strains may ameliorate pain and provide global relief (B.
infantis 35624), Lactobacillus reuteri may improve colicky
symptoms within one week
• 108 cfu of the freeze-dried probiotic bacteria B. infantis spec.
Prevention of Carcinogenesis &
Tumor Growth
• Prevention or delay in tumor development by lactobacilli
• By binding to Mutagenic compound in the intestine & decreasing
absorption of these mutagenic heterocyclic amines.
• Lactobacillus (GG) decrease activity of following and helps to prevent
procarcinogen to carcinogen
• β glucoronidase
• Nitroreductase
• Cholylglycine hydrolase
• SCFA like Butyrate is the preferred energy substrate for the
colonocyte, it provides fuel (nutrition) for ileal and colonic epithelial
cells, which help maintain the integrity of the colon.
• Reduction in DNA damage and a reduction in cell proliferation in colon
biopsies.
Immunoregulation
• Probiotics helps to Increase IgA production by B- cells
• Endowed with antiviral property, induce NO synthase (a virus
infected cell death mechanism)
• Production of gamma intereferon, TNF-alph,IL-1 by mononuclear
cells incubated with Lactobacillus. Increase cytotoxic potential of
NK cells, increasing IL-10 synthesis thus preventing acute
infectious disease (nosocomial diarrhea in children, influenza
episodes in winter)
• Adherant Lactobacilli and Bifidobacteria significantly increase
phagacytosis.
Hepatic encephalopathy –
• By reducing level of ammonia in blood
• synbiotic preparation-four probiotic strains and four fermentable
fibers, including inulin and resistant starch reverse it in 30 days
Obesity-
• Fructans, daily consumption helps in reducing appetite. SCFA-
stimulated secretion of gut peptides such as glucagon-like
peptide (GLP)-1, peptide YY (PYY) and oxytomodulin and reduced
secretion of ghrelin, all of which are secreted by endocrine-type
cells in the mucosa.
• lowering body weight or fat mass, and improving glucose
tolerance
Reduces the incidence and severity of sepsis in intensive care units
Challenges
• Retention of viability of the probiotic bacteria
• A serious problem of shelf instability had been encountered with dried Cultures.
difficulty backing up label claims
• Refrigerated products also have short lives due to negative effects of low temperature
and formation of crystals on bacterial cells
• Manufacturer must incorporate an excess of cells at the time the tablets are
manufactured. This practice increases the cost and makes the use instructions
inaccurate
• Extreme temperatures, high pressure, shear forces can destroy the preperations
• Survival of most bifidobacteria in most dairy products is poor due to low pH and/or
exposure to oxygen
• Difficulty in assessment of efficacy of pro and prebiotics
M.S. Thantsha et al.Probiotics – What They Are, their Benefits and Challengeswww.intechopen.com
Regulatory guidelines
S.No Parameter Indian regulatory guidelines
1 Regulatory category of
probiotics
Drugs and functional foods
2 Regulatory authority for
approval
1. Functional food are regulated by regulated by
PFA (Prevention of Food Adulteration Act) as per
The Food Safety and Standards
Act (FSSA).
2. Drugs are regulated by FDA.
3 Recommended
regulatory guidelines
Guidelines are recommended for probiotics in
food and major stress is on identification and
evaluation of probiotic strain along with health
claims and labeling claims.
4 Assessment of safety
parameters
FDA is responsible for the safety of drugs and food
safety is responsibility of FSSA. ICMR guidelines
can also be used to identify and evaluate safety.
5 Requirements for approval Drugs:
1. Clinical data
2. Data to support study of products in
humans: CMC, Stability, Pharmacology/
toxicology
Functional foods:
1. Strain identification
2. Functional characterization
3. Safety assessment
4. Labeling requirement
6 Available probiotic
products
Sporolac, Yogurt, Darolac,
Biglac, Bifilac etc.
Biological products require pre-market review and
approval by the FDA; however, dietary supplements
do not
Int. Jn of Biotechnology for Wellness Industries, 2013 Vol. 2, No. 2
Differences
PREBIOTICS PROBIOTICS
PREBIOTICS are a special form of dietary
fiber
PROBIOTICS are live bacteria in yogurt, dairy
products and pills. There are hundreds of
probiotic species available. Which of the
hundreds of available probiotics is best is still
unknown.
PREBIOTIC powders are not affected by heat,
cold, acid or time
PROBIOTIC bacteria must be kept alive. They
may be killed by heat, stomach acid or simply
die with time
Wide range of health benefits to the
otherwise healthy person. Most of these
have been medically proven
PROBIOTICS are still not clearly known to
provide health benefits to the otherwise
healthy
Nourish the good bacteria that everyone
already has in their gut
Must compete with the over 1000 bacteria
species already in the gut
May be helpful or preventative for irritable
bowel (IBS), or inflammatory bowel disease
(Crohn’s Disease,Ulcerative Colitis), colon
polyps and cancer and those people with a
leaky gut
Certain PROBIOTIC species have been shown
to be helpful for irritable bowel disease and
for recurrence of certain bowel infections
such as C. difficile
Prebiotic index
• questions can be formulated as follows:
• 1) Are the different prebiotics equally effective?
• 2) Can a dose-effect relation be established?
• To answer this, required thing is PI
• Increase in the absolute number of bifidobacteria
expressed(cfu per gm of feces) divided by the daily dose of
prebiotic ingested(gms)
• For inulin-type fructans, such a prebiotic index is of the order
of a few (average . 4.00 ± 0.082) 108 cfu/g,
jn.nutrition.org Effects of Probiotics and Prebiotics
Symbiosis
• Commensalism is a class of relationship between two organisms
•  Mutualism: (facultative) both organisms benefit
 Parasitism: (obligate) one organism benefits and the other one is
harmed.
Synbiotics
• nutritional supplements combining probiotics and prebiotics in a form of
synergism. term "synbiotic" be used only if the net health benefit is
synergistic
• Probiotics may colonise the upper intestine to avoid the adhering of
pathogens to the intestinal tract and may help in digestion and prebiotic
stimulate the microflora in the large intestine, combination thus works
separately in the small and large intestine, but synergistically as they increase
the overal gut health
Eg: Bifidobacteria and fructo-oligosaccharides (FOS)
Jn of Leukocyte Biology Volume 89, May 2011
Postbiotics
 Probiotics provide benefit by way of metabolites such as enzymes, peptides,
bacterions, and organic acids, called postbiotics. So culture supernatant of
these bacteria mediates the immunomodulatory effect conferred to the host
 They are important anions in the colonic lumen, affecting both Colonocyte
Morphology (Proliferation / Differentiation) & Function (Tight Colonic Junction /
Inflammatory Suppression).
 Postbiotics biggest benefit? Nutrients, enzymes and peptides deliver an overall
anti-inflammatory effect to slow or halt disease process in its tracks.
 Use of postbiotic components as a safer alternative for clinical applications,
especially in chronic inflammatory conditions like inflammatory bowel disease,
where probiotics have not yet given encouraging results as far as induction of
remission is concerned.
Probiotics + prebiotics + postbiotics
The Probiotic Paradox
• The Probiotic Paradox is that both live and dead bacteria in
probiotic products can generate biological responses
• Live probiotic cells influence both the gastrointestinal microflora
and the immune response whilst the components of dead cells
exert an anti-inflammatory response in the gastrointestinal tract
• Difficult to assess the relative proportions of live and dead cells in
a probiotic culture.
• Contribute to the variation in response often seen with live
probiotic cultures
• Use of dead probiotics as biological response modifiers has
several attractive advantages; such products would be very safe
and have a long shelf-life.
Conclusion
• Advocated by many health care professionals because of their
evidence based health benefits in specific clinical scenarios
• Prevention and alleviation of nonspecific and irregular complaints
of the gastrointestinal tracts in healthy people
• Prebiotics have great potential as agents to improve or maintain
a balanced intestinal microflora to enhance health and wellbeing.
• Still the rational usage, selection and design of probiotics remain
important challenges for the scientific community in concern with
their safety factors and an urgent need to address the quality,
safety and efficacy issues of probiotics
References
• Probiotics and prebiotics World Gastroenterology
Organisation, 2008
• Probiotics – What They Are,Their Benefits and Challenges.
New Advances in the Basic and Clinical Gastroenterology
www.intechopen.com.
• Comparative Insight of Regulatory Guidelines for Probiotics
in USA, India and Malaysia: A Critical Review. International
Journal of Biotechnology for Wellness Industries, 2013, 2, 51-
64.
• Prebiotics and Probiotics: A Critical Analysis by Vijay
Prakash. Chap 57
Summary
Microflora Mode of action
Bifidobacteria species Reduced incidence of neonatal necrotizing enterocolitis
Treatment of rotavirus diarrhea, balancing of intestinal
microflora, treatment of viral diarrhea
Enterococcus faecium Decreased duration of acute diarrhoea from gastroenteritis
Lactobacillus strains pouchitis
Lactose digestion improved, decreased diarrhoea and symptoms
of intolerance in lactose intolerant individuals, children with
diarrhoea, and individuals with short-bowel syndrome, as an
adjunct to antibiotics
Improved mucosal immune function, mucin secretion and
prevention of disease
Vaccine adjuvant, adherence to human intestinal cells, balancing
of intestinal microflora
Saccharomyces boulardii Prevention of traveler’s diarrhea, prevention and
treatment of C. difficile diarrhea, Shortened
the duration of acute gastroenteritis
Bacillus Sp Heat stable oral vaccine delivery, prophylactics and
prevention of
gastrointestinal infections
Pediococcus Enhanced immune responses against infectious
coccidioidal diseases
Probiotics and prebiotics related to pharmacology
Probiotics and prebiotics related to pharmacology

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Probiotics and prebiotics related to pharmacology

  • 2. Overview of Presentation • Introduction • History • Facts about intestine • Probiotics • Definition • Criteria • Mechanism of action • Safety issues • Assosiated benefits • Drug interactions • Precautions & contraindications • Prebiotics • Definition • Criteria • Mechanism of action • Potential benefits • Assosiated risks • Clinical applications • Regulatory guidelines • Challenges • Postbiotics, synbiotics etc. • Conclusion
  • 3. Introduction • Quality healthcare is the foundation of any prosperous nation. • Long before the existence of microorganisms was known or recognized, fermented products were used therapeutically, to treat colds, fevers, and ailments of the gastro intestinal tract such as constipation and diarrhea. • Research has shown that Probiotics and Prebiotics are useful in achieving positive health effects and well being to the host. • It however gained momentum only recently. • India is also fast emerging as a potential market for these. • Probiotic product industries in India were estimated to be around Rs 20.6 million with a projected annual growth rate of 22.6% until 2015
  • 4. Intestine is a paradise of disease “Death sits in the bowels; a bad digestion is the root of all evil” - Hippocrates, ca. 400 BC
  • 5. 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 hypothesised that consuming large amounts of fermented milk products that contained Lactobacillus bacteria (“soured milk”) could prolong and improve the quality of life.
  • 6. 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 in 1954 to indicate substances that were required for a healthy life • Probiotics term coined in 1965 by Lilly And Stillwell • Japanese were the first to recognise the value of non-digestible oligosaccharides • It was not until 1995 that the scientific concept for human gut microbiota modulation by “prebiotics” was introduced
  • 7. • 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, Payer’s patches and mesenteric lymph nodes) • Our Intestine = 400 square meter surface… i.e. the surface area of a tennis court Largest immune organ
  • 8. • 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, Bifidis and Acidophilus comprise the majority of healthy bacteria in the colon along with other disease producing bacteria. • Normal ratio is 4:1. Facts about Intestine
  • 9. • Dysbiosis is the abnormal microbial colonization of the intestine , where changes in quantity and quality of flora become pathological & harmful. • Common cause of dysbiosis: • Antibiotic therapy • Others are fast paced lifestyle, stress, food habits, chlorine in drinking water, Alcohol intake and cigarrete smoking • Age • Autoimmune conditions (rheumatoid), IBD etc. Dysbiosis
  • 10. Terminologies • Prebiotics (before life)- A substance that cannot be digested but thus promote the growth of beneficial bacteria and probiotics. • Probiotics (for life)- live microorganisms which when administered in adequate amounts confer a health benefit on the host. • Synbiotics (plus life)- substance containing both above. • Antibiotics (against life)-A substance that can destroy or inhibit the growth of other microorganisms. Antibiotics are widely used in the prevention and treatment of infectious diseases.
  • 11. Terminology • Biotherapeutic agent: A therapeutic material produced using biological means, including recombinant DNA technology eg. interferons, interleukins, and growth factors • Functional foods- defined as products that are similar in appearance to conventional foods that are consumed as part of a normal diet and have demonstrated physiological benefits, and/or have the potential to reduce the risk of chronic disease beyond nutritive function, i.e. they contain bioactive compounds.
  • 12. • 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 :- Engineered grain, cereals supplemented with vitamins or minerals, genetically manipulated soybean and canola oil without trans-fatty acids Nutraceuticals
  • 13. 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
  • 15. Definition • Probiotics - live microorganisms which, when administered in adequate amounts, confer a health benefit on the host ( FAO/WHO 2001)
  • 16. Characteristics of Effective Probiotics Probiotic microorganisms should be: • Able to Maintain good viability • Able to survive the passage through the digestive system • Must not deconjugate bile salts • Able to attach to the intestinal epithelia and colonize • Carry no antibiotic resistance genes that can be transferred to pathogens • Able to utilize the nutrients and substrates in a normal diet • Capable of exerting a beneficial effect on the host
  • 17. • Produce Antimicrobial Compound • Organic acids • Hydrogen peroxide • Carbon dioxide • Diacetyl • Acetaldehyde • Bacteriocins • To be safe, noninvasive, noncarcinogenic and nonpathogenic • Coaggregate to form a normal balanced flora • Strain must not induce an immune reaction in the host
  • 19. Mechanism of action (1) Competition for dietary ingredients as growth substrates, (2) Bioconversion of, for example, sugars into fermentation products (3) Production of growth substrates, for example vitamins, for other bacteria (4) Direct antagonism by bacteriocins (5) Competitive exclusion for binding sites (6) Improved barrier function (7) Reduction of inflammation, thus altering intestinal properties (8) stimulation of innate immune response (by unknown mechanisms)
  • 20.
  • 21.
  • 22. Beneficial effects of probiotics • Immunological benefits- • Activate local macrophages to increase antigen presentation to B lymphocytes and increase IgA production locally • Modulate cytokine profile • Induce hyporesponsiveness to food allergies • Lower blood ammonia levels • Lower serum cholesterol levels • Produce vitamins eg: vitamin B,K, folic acid • Promote normalization of intestinal flora after antibiotic therapy • Act as immunomodulator- by promoting attacks on malignant cells
  • 23. • Nonimmunologic benefits- • Digest food and compete for nutrients with pathogens • Alter local pH • Produce bacteriocin to inhibit pathogen • Scavange superoxide radical • Stimulate epithelial mucin production • Enhance intestinal barrier function • Compete for adhesion with pathogen • Modify pathogen derived toxins
  • 24. Forms and Dosage of probiotics • Most common forms for probiotics are dairy products and probiotic-fortified foods • Formulations: drops, chewable tablets, lozenges, capsules, straws, bottle caps and bacteria in freeze-dried form are also available • Sporolac, ViBact, Darolac, Biglac, Bifilac etc. • Dose needed depending on the strain and product. • Over the counter dose is 1-10 billion cfu/dose • Bifidobacterium infantis for IBS-100 million cfu/dose
  • 25. • Dose-Varies greatly with product • Live and active cultureYogurts must contain >108 [100 million] • L.rhamnosus GG has 10 billion • Duration: probiotics are taken daily for 2weeks to 2 months • Often taken empty stomach • If taken along with antibiotics, gap of 2 hrs.
  • 26. Fecal microbiota transplantation (FMT) • FMT is the process of transplantation of fecal bacteria from a healthy individual into a recipient patient for the treatment of C. difficile infection. • The procedure can be carried out via enema (simplest and most acceptable) through the colonoscope, or through a nasogastric or nasoduodenal tube. • Most patients with C. difficile infection recover and have it eradicated after just one treatment.
  • 27. Established Probiotics • The majority of probiotics are incorporated into dairy products such as milk powders, yoghurt, cheese and ice cream • Non-dairy products such as malt-based beverages and fruit juices meat sausages, capsules, and freeze-dried preparations. • Most common micro-organisms which are used:- BIFIDOBACTERIUM • Infantis (breastmilk) • lactis • longum • breve • Bifidum LACTOBACILLUS(first and largest group) • reuteri • casei • ramnosus • Acidophilus LACTOCOCCUS, SACCHAROMYCES, STREPTOCOCCUS,THERMOPHILUS, ENTEROCOCCUS
  • 28. Drug Interactions • Concurrent administration of antibiotics could kill a large number of the organisms, reducing the efficacy of the Lactobacillus and Bifidobacterium species. Patients should be instructed to separate administration of antibiotics from these bacteria-derived probiotics by at least two hours. • S. boulardii might interact with antifungals, reducing the efficacy of this probiotic
  • 29. Precautions and Contraindications • Critically ill or severely immunocompromised patients, probiotic strains of Lactobacillus have been reported to cause bacteraemia, endocarditis, meningitis. • Short-bowel syndrome can have bacteremia, possibly due to altered gut integrity. • Caution is also taken in patients with central venous catheters. • Lactobacillus preparations are contraindicated in persons with a hypersensitivity to lactose or milk. • S. boulardii is contraindicated in patients with a yeast allergy. • No contraindications are listed for bifidobacteria, since most species are considered nonpathogenic and nontoxigenic.
  • 31. Definition • Prebiotics are defined as nondigestible food ingredients (oligosaccarides) that are resistant to digestion and absorption , are fermented by cecal /colonic microbiota, and selectively stimulate growth and/or activity of bacteria that contribute to colonic and host health • Prebiotics; are simply speaking the preferential “FOOD” for Friendly Beneficial Bacteria colonizing the digestive tract. • They are dietary supplements that play a role in Balancing the Intestinal Mucosal Immune System Colonic food
  • 32. Criteria for eligibility as prebiotics 1. Resistance to gastric acidity, to hydrolysis by mammalian enzymes, and to gastrointestinal absorption 2. Selective stimulation of the growth and/or activity of intestinal bacteria that contribute to health and well- being 3. Fermentation by intestinal microflora; to produce SCFA & gas. 4. Induce LUMINAL or SYSTEMIC beneficial effects. Gibson et al., 2007
  • 33. Established prebiotics Name Obtained from/manufactured by Inulin Extraction from chicory root, Wheat, banana, onions, 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 Original they represent the third largest component of Human Milk 20 - 23 gm/l in colostrum & 12- 14 gm/ in mature milk Aliment Pharmacol Ther 24, 701–714
  • 34. Potential prebiotics • Mannanoligosaccharides (yeast cell wall) • Glucooligosaccharides • Lactose • Arabinogalactan (radishes, carrots, tomatoes and wheat) • Polydextrose • Glucuronic acid • Sugar alcohols • Pectin oligosaccharides (apple pectin, citrus pectin) • Whole grains • gum arabic, guar gum • Potential applications for prebiotics as food ingredients to improve the gastrointestinal health include beverages, bakery products, table spreads, sauces, infant formulae and weaning foods, cereals, confectionery, snack bars, soups, salad dressings and dairy products
  • 35. Mechanism of action • Mechanisms by which prebiotics provide health benefits • Increases the amount of lactic acid producing bacteria (lactobacilli and bifidobacteria) • Increases the amount of Short Chain Fatty Acids (SCFAs)- Butyrate, Acetate, Lactate etc… • Activates carbohydrate receptor immune cells Journal of Family Ecology and Consumer Sciences, Vol 35, 2007
  • 36.
  • 37. Potential benefits 1. Fermentation of oligofructose in the colon results in a large number of physiologic effects • Increase mineral absorption( as they do not bind them) • Shortening gastrointestinal transit time • lowering blood lipid levels (decrease requirement of fat in food because of their gel like property) • Increasing fecal weight (decreases constipation) • The increase in colonic bifidobacteria has been assumed to benefit human health by • producing compounds to inhibit potential pathogens • reducing blood ammonia levels • producing vitamins and digestive enzymes.
  • 38. 2. Production of short chain fatty acids (SCFA) eg: Acetate, Propionate, and Butyrate and Lactic acid • Increase water and sodium absorption • Increase mucosal blood flow and mucosal cell proliferation hence mucus production • Improvement of the epithelial barrier function (by regulating tight junction protein genes) • Promoting homeostatic immunoregulation by the induction of interleukin (IL)-10, transforming growth factor (TGF)-b and by the inhibition of tumor necrosis factor (TNF)-a and IL-12 synthesis • Prevent colon inflammation • Decrease lymphocyte proliferation • Inhibit C.K production • Induce T lymphocyte apoptosis • Activates G-Protein coupled receptors (supply fuel to immune cells)
  • 39. Associated risks • Fructose malabsorption (with FOS & Inulin) • Can irritate GIT if taken in high dose and Ca+2 content is low (produced lactic acid irritates wall of intestine) • GI Disturbances: • Constipation/ Diarrhoea • Abdominal pain • Flatulence • Bloating This is advantageous as it allows a relatively broad “therapeutic window”
  • 40. Forms and dosage • Ispaghula husk as a loose powder. A good dose is 10 grams (= 2 heaped teaspoons) twice daily. For IBS • FOS (fructooligosaccharides) loose powder. A good dose is 2.5 grams (= 1 level teaspoon) twice daily. • Inulin powder/syrups 2.5 grams (= 1 level teaspoon) twice daily (better prebiotic than FOS) • GOS (Galactooligosaccharides) 5 grams daily. • Butyric acid capsules- Provide most of the benefits of probiotics, without actually taking probiotics for upset of gut • Start with lower doses for a few days, otherwise may experienced some constipation. • Caution is taken with antibacterial herbs or supplements that are taken alongwith, which may inhibit the good bacteria as well as the bad. The Wonders of Prebiotic.Hip, Oct 6, 2010.
  • 41. Clinical application of probiotics and prebiotics Proven Benefit • Diarrheal Illness (viral) - treatment and prevention • Prevention of antibiotic-associated diarrhea • Constipation Suggested Benefit • Food allergies • Inflammatory bowel disease • Lactose intolerance • Treatment of recurrent Clostridium dificile infection (Clostridium dificile is a bacteria that can cause serious infection in the intestine). • Eczema
  • 42. Holds Promise • Cystic fibrosis • Dyslipidemia/ Cardiovascular dieases • Liver disease • Rheumatoid arthritis • Traveler’s diarrhea / bacterial enteritis • Vaccine immuno-augmentation • Genitourinary tract infections • Necrotising enterocolitis • Allergic rhinitis • Asthma • Attention deficit disorder (ADD) / Attention deficit hyperactivity disorder (ADHD) • Autism • Colic • Colon cancer prevention • Obesity
  • 43. Treating Infection Antibiotic Associated Diarrhea • Associated with C.difficile which may cause pseudomembraneous colitis • Lactobacillus GG successful in eradicating C.difficile • Saccharomyces boulardii in DBC study reduced recurrence from 22% to 9.5% • Useful in reducing the severity and duration of acute infectious diarrhea in children • Probiotics used in prevention and as adjuvant therapy in AAD. Guandalini. J Clin Gastroenterol, 2008
  • 44. Childhood diarrhea • Metanalysis revealed length of course of childhood diarrhea reduced 1–1.5 d, decreased frequency of infections, decreased shedding of rotaviruses or promotion of systemic or local immune response, increase in the production of rotavirus-specific antibodies when probiotic added to treatment • Probiotics given as suspended in oral rehydration solutions • By stimulating rotavirus specific IgA production of through B cells Traveller’s diarrhea • Incidence reduced from 71 to 43% in tourist study with S.boulardii Floch. JClinGastro 2005;40:275
  • 45. Allergy • Atopic eczema, Dermatitis, Allergic rhinitis, Asthma, food allergies with milk, eggs, peanuts, tree nuts, soy, wheat gluten, fish, shellfish and shrimp • Atopic children tend to have a degree of dysbiosis, with more clostridia and fewer bifidobacteria •  IgE thought to be caused by a skewed balance between Th1 and T helper type 2 cells • Probiotics improving the Th1/Th2 balance in favour of a predominance of Th1 cells • Lactobacillus GG has been used to treat cow milk allergy and atopic eczema • prebiotic-supplemented infant formula reduce susceptibility to atopy but that the benefits persist up to 2 years of age
  • 46. Genitourinary • Recurrent Candida Vaginitis and Bacterial Vaginosis have been successfully treated by administration of both oral and vaginal Lactobacilli • Vaginal suppositories with 1 billion cfu • Recent study in 185 Nigerian woman with vaginosis – L.rhamnosus + L.reuteri + metronidazole more effective than metronidazole alone – 88% to 40%* Floch. JClinGastro 2005;40:275
  • 47. IBD • IBD is associated with a breakdown of the normal barrier function provided by the gut epithelial lining and its associated mucus commensal bacteria might be altered. • Use of probiotics and prebiotics giving good results in maintaining remission in UC but not of much in CD • Usually 1x109, or 1 billion colony forming units (CFU) is a good daily dose
  • 48. IBS • Prebiotics relieve constipating symptoms- • Increased bacterial mass and osmotic water-binding capacity making stools bulky • Increased stool frequency and softer stools • Butyrate, have a positive effect on the endothelium and on peristalsis, which improves transit • A reduction in abdominal bloating and flatulence as a result of probiotic treatments is a consistent finding • some strains may ameliorate pain and provide global relief (B. infantis 35624), Lactobacillus reuteri may improve colicky symptoms within one week • 108 cfu of the freeze-dried probiotic bacteria B. infantis spec.
  • 49. Prevention of Carcinogenesis & Tumor Growth • Prevention or delay in tumor development by lactobacilli • By binding to Mutagenic compound in the intestine & decreasing absorption of these mutagenic heterocyclic amines. • Lactobacillus (GG) decrease activity of following and helps to prevent procarcinogen to carcinogen • β glucoronidase • Nitroreductase • Cholylglycine hydrolase • SCFA like Butyrate is the preferred energy substrate for the colonocyte, it provides fuel (nutrition) for ileal and colonic epithelial cells, which help maintain the integrity of the colon. • Reduction in DNA damage and a reduction in cell proliferation in colon biopsies.
  • 50. Immunoregulation • Probiotics helps to Increase IgA production by B- cells • Endowed with antiviral property, induce NO synthase (a virus infected cell death mechanism) • Production of gamma intereferon, TNF-alph,IL-1 by mononuclear cells incubated with Lactobacillus. Increase cytotoxic potential of NK cells, increasing IL-10 synthesis thus preventing acute infectious disease (nosocomial diarrhea in children, influenza episodes in winter) • Adherant Lactobacilli and Bifidobacteria significantly increase phagacytosis.
  • 51. Hepatic encephalopathy – • By reducing level of ammonia in blood • synbiotic preparation-four probiotic strains and four fermentable fibers, including inulin and resistant starch reverse it in 30 days Obesity- • Fructans, daily consumption helps in reducing appetite. SCFA- stimulated secretion of gut peptides such as glucagon-like peptide (GLP)-1, peptide YY (PYY) and oxytomodulin and reduced secretion of ghrelin, all of which are secreted by endocrine-type cells in the mucosa. • lowering body weight or fat mass, and improving glucose tolerance Reduces the incidence and severity of sepsis in intensive care units
  • 52. Challenges • Retention of viability of the probiotic bacteria • A serious problem of shelf instability had been encountered with dried Cultures. difficulty backing up label claims • Refrigerated products also have short lives due to negative effects of low temperature and formation of crystals on bacterial cells • Manufacturer must incorporate an excess of cells at the time the tablets are manufactured. This practice increases the cost and makes the use instructions inaccurate • Extreme temperatures, high pressure, shear forces can destroy the preperations • Survival of most bifidobacteria in most dairy products is poor due to low pH and/or exposure to oxygen • Difficulty in assessment of efficacy of pro and prebiotics M.S. Thantsha et al.Probiotics – What They Are, their Benefits and Challengeswww.intechopen.com
  • 53. Regulatory guidelines S.No Parameter Indian regulatory guidelines 1 Regulatory category of probiotics Drugs and functional foods 2 Regulatory authority for approval 1. Functional food are regulated by regulated by PFA (Prevention of Food Adulteration Act) as per The Food Safety and Standards Act (FSSA). 2. Drugs are regulated by FDA. 3 Recommended regulatory guidelines Guidelines are recommended for probiotics in food and major stress is on identification and evaluation of probiotic strain along with health claims and labeling claims. 4 Assessment of safety parameters FDA is responsible for the safety of drugs and food safety is responsibility of FSSA. ICMR guidelines can also be used to identify and evaluate safety.
  • 54. 5 Requirements for approval Drugs: 1. Clinical data 2. Data to support study of products in humans: CMC, Stability, Pharmacology/ toxicology Functional foods: 1. Strain identification 2. Functional characterization 3. Safety assessment 4. Labeling requirement 6 Available probiotic products Sporolac, Yogurt, Darolac, Biglac, Bifilac etc. Biological products require pre-market review and approval by the FDA; however, dietary supplements do not Int. Jn of Biotechnology for Wellness Industries, 2013 Vol. 2, No. 2
  • 55. Differences PREBIOTICS PROBIOTICS PREBIOTICS are a special form of dietary fiber PROBIOTICS are live bacteria in yogurt, dairy products and pills. There are hundreds of probiotic species available. Which of the hundreds of available probiotics is best is still unknown. PREBIOTIC powders are not affected by heat, cold, acid or time PROBIOTIC bacteria must be kept alive. They may be killed by heat, stomach acid or simply die with time Wide range of health benefits to the otherwise healthy person. Most of these have been medically proven PROBIOTICS are still not clearly known to provide health benefits to the otherwise healthy Nourish the good bacteria that everyone already has in their gut Must compete with the over 1000 bacteria species already in the gut May be helpful or preventative for irritable bowel (IBS), or inflammatory bowel disease (Crohn’s Disease,Ulcerative Colitis), colon polyps and cancer and those people with a leaky gut Certain PROBIOTIC species have been shown to be helpful for irritable bowel disease and for recurrence of certain bowel infections such as C. difficile
  • 56. Prebiotic index • questions can be formulated as follows: • 1) Are the different prebiotics equally effective? • 2) Can a dose-effect relation be established? • To answer this, required thing is PI • Increase in the absolute number of bifidobacteria expressed(cfu per gm of feces) divided by the daily dose of prebiotic ingested(gms) • For inulin-type fructans, such a prebiotic index is of the order of a few (average . 4.00 ± 0.082) 108 cfu/g, jn.nutrition.org Effects of Probiotics and Prebiotics
  • 57. Symbiosis • Commensalism is a class of relationship between two organisms •  Mutualism: (facultative) both organisms benefit  Parasitism: (obligate) one organism benefits and the other one is harmed. Synbiotics • nutritional supplements combining probiotics and prebiotics in a form of synergism. term "synbiotic" be used only if the net health benefit is synergistic • Probiotics may colonise the upper intestine to avoid the adhering of pathogens to the intestinal tract and may help in digestion and prebiotic stimulate the microflora in the large intestine, combination thus works separately in the small and large intestine, but synergistically as they increase the overal gut health Eg: Bifidobacteria and fructo-oligosaccharides (FOS) Jn of Leukocyte Biology Volume 89, May 2011
  • 58. Postbiotics  Probiotics provide benefit by way of metabolites such as enzymes, peptides, bacterions, and organic acids, called postbiotics. So culture supernatant of these bacteria mediates the immunomodulatory effect conferred to the host  They are important anions in the colonic lumen, affecting both Colonocyte Morphology (Proliferation / Differentiation) & Function (Tight Colonic Junction / Inflammatory Suppression).  Postbiotics biggest benefit? Nutrients, enzymes and peptides deliver an overall anti-inflammatory effect to slow or halt disease process in its tracks.  Use of postbiotic components as a safer alternative for clinical applications, especially in chronic inflammatory conditions like inflammatory bowel disease, where probiotics have not yet given encouraging results as far as induction of remission is concerned. Probiotics + prebiotics + postbiotics
  • 59. The Probiotic Paradox • The Probiotic Paradox is that both live and dead bacteria in probiotic products can generate biological responses • Live probiotic cells influence both the gastrointestinal microflora and the immune response whilst the components of dead cells exert an anti-inflammatory response in the gastrointestinal tract • Difficult to assess the relative proportions of live and dead cells in a probiotic culture. • Contribute to the variation in response often seen with live probiotic cultures • Use of dead probiotics as biological response modifiers has several attractive advantages; such products would be very safe and have a long shelf-life.
  • 60. Conclusion • Advocated by many health care professionals because of their evidence based health benefits in specific clinical scenarios • Prevention and alleviation of nonspecific and irregular complaints of the gastrointestinal tracts in healthy people • Prebiotics have great potential as agents to improve or maintain a balanced intestinal microflora to enhance health and wellbeing. • Still the rational usage, selection and design of probiotics remain important challenges for the scientific community in concern with their safety factors and an urgent need to address the quality, safety and efficacy issues of probiotics
  • 61. References • Probiotics and prebiotics World Gastroenterology Organisation, 2008 • Probiotics – What They Are,Their Benefits and Challenges. New Advances in the Basic and Clinical Gastroenterology www.intechopen.com. • Comparative Insight of Regulatory Guidelines for Probiotics in USA, India and Malaysia: A Critical Review. International Journal of Biotechnology for Wellness Industries, 2013, 2, 51- 64. • Prebiotics and Probiotics: A Critical Analysis by Vijay Prakash. Chap 57
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  • 64.
  • 65. Summary Microflora Mode of action Bifidobacteria species Reduced incidence of neonatal necrotizing enterocolitis Treatment of rotavirus diarrhea, balancing of intestinal microflora, treatment of viral diarrhea Enterococcus faecium Decreased duration of acute diarrhoea from gastroenteritis Lactobacillus strains pouchitis Lactose digestion improved, decreased diarrhoea and symptoms of intolerance in lactose intolerant individuals, children with diarrhoea, and individuals with short-bowel syndrome, as an adjunct to antibiotics Improved mucosal immune function, mucin secretion and prevention of disease Vaccine adjuvant, adherence to human intestinal cells, balancing of intestinal microflora
  • 66. Saccharomyces boulardii Prevention of traveler’s diarrhea, prevention and treatment of C. difficile diarrhea, Shortened the duration of acute gastroenteritis Bacillus Sp Heat stable oral vaccine delivery, prophylactics and prevention of gastrointestinal infections Pediococcus Enhanced immune responses against infectious coccidioidal diseases

Notas del editor

  1. The prebiotic concept developed more recently . initially in animal feed where their addition to the feed of piglets helped relieve and prevent scouring (diarrhoea).
  2. When intestinal flora equilibrium is disturbed
  3. Probiotic bacteria can interfere with the growth or survival of pathogenic micro-organisms in the gut lumen (level 1). Probiotic bacteria can improve the mucosal barrier function and mucosal immune system (level 2) and, beyond the gut, have an effect on the systemic immune system, as well as other cell and organ systems such as liver and brain (level 3)
  4. Prebiotics pass through the upper GIT unfermented and are only utilized in the colon and are therefore called ‘colonic food’ Scientific studies in Japan indicated that consumption of prebiotics increases the populations of bifidobacteria and other beneficial microorganisms even in the absence of probiotics in diet
  5. Not all dietary carbohydrates are prebiotics, and clear criteria need to be established for classifying a food ingredient as a prebiotic.
  6. Honey, fruits and vegetables such as artichoke, asparagus, banana, barley, chicory, garlic, leeks, oats, onion, rye, soybeans, tomatoes and wheat are sources of non-digestible oligosaccharides, Taking foods containing prebiotic oligosaccharides is not enough for modulation of gut flora as they are present in only small concentrations in these foods. Instead, prebiotics are extracted from these foods and transferred into more commonly ingested foodstuffs like biscuits and other carbohydrate based materials (
  7. Butyrate helps in transcription. Significantly affect histone acetylation
  8. Another option is taking activated charcoal tablets with prebiotics; charcoal significantly reduces intestinal gas. This might eliminate the pain produced from bloating. Charcoal also absorbs toxins, so it is another useful detoxifier (but note that charcoal can also absorb some of your medications, if you are taking any
  9. A study showed that a decrease in Bifidobacteria population occurs within 2 or 3 week of stopping FOS supplementation. So the message here is to keeping taking your prebiotics, in order to maintain friendly gut flora populations, and prevent the bad bacteria from re-establishing themselves.
  10. results are promising but not yet conclusive.
  11. barrier or if a breakdown of the barrier allows inflammation to develop is not clear
  12. Many active cultures die during manufacturing, storage or transport of the finished product. and also during the passage to the intestine. The numbers of viable bacteria continually decrease with time during refrigerated storage (Excesses of 50 to 200 % cells have been incorporated into products in an attempt to make-up for cells that die during storage
  13. Host-Bacteria interaction responsible for the effectiveness of gut immune related mechanisms.
  14. For a probiotic to work it must arrive alive. In practice it may not be possible to feed only live bacteria to a subject. There will always be the possibility that an unknown amount of dead cells are being administered with the live cells.
  15. If comparative information is to be gathered on structure-function relations in prebiotic oligosaccharides, a rigorous approach to the evaluation of these molecules will be required. Such thorough comparative studies will allow intelligent choices in incorporating prebiotics into functional foods a