Probiotics and prebiotics

in pediatric practice
APEPEOKHA
June 04,2010
outline
 Introduction
Historical perspective
Definition
Normal intestinal micro ecology
Types
Key properties of probiotics
Mechanism
Uses
Drawbacks
Prebiotics
Conclusion
Introduction
The concept of probiotics evolved at the turn of the
20th century from a hypothesis first proposed by
Nobel Prize winning Russian scientist Elie
Metchnikoff (Bibel, 1988)
He suggested that the long, healthy life of Bulgarian
peasants resulted from their consumption of
fermented milk products.
He believed that when consumed, the fermenting
bacillus (Lactobacillus) positively influenced the
microflora of the colon.
Modern civilisation is faced with a progressive
increase in immune-mediated gut-related health
problems such as allergies, autoimmune and
inflammatory diseases.
Microbial stimulation is required for the maturation
of the immune system to fight allergic disease.
The human diet once contained several thousand
times more bacteria than it does today
Industrial processing has led to extensive
pasteurisation and sterilisation.
Probiotics provide a safe microbial stimulus for the
maturation of the gut-associated lymphoid tissue.
A Brief History of Probiotics
Metchnikoff – 1907 – ingesting yogurt with
Lactobacilli reduces toxic bacteria of the gut and
prolongs life
Kipeloff – 1926 – stressed importance of Lactobacillus
acidophilus for good health
Rettger – 1930’s – early clinical application of
Lactobacillus
Parker – 1974 – 1st to use the term probiotics
Fuller – 1989 – defined probiotics
Definition
Probiotics are defined as live microbial food ingredients
that have a beneficial effect on human health (Salminen et
al., 1998).

prebiotics—non digestible food ingredients that

selectively stimulate the growth and activity of beneficial
microorganisms already in people’s colons. In common
terms, prebiotics are food for bacterial species that are
considered beneficial for health and well-being.
When probiotics and prebiotics are mixed together, they
form a synbiotic.
Intestinal Flora: A symbiotic relationship
with the host
Human GI tract contains 10x more bacteria (1014)
than eukaryotic cells in the body
Protects the host
Stimulates immune function
Produces antimicrobial substances
Trophic effect on intestinal epithelium
Maintains the enterohepatic circulation of bile acids
Involved in metabolic processes (i.e., fermentation)
in the colon
Intestinal Microflora: Location & Prevalence
Rare in the esophagus
Uncommon in the stomach
primarily gram (+)
102 - 104
105 in the jejunum – primarily aerobes
1010 – 1012 in the colon
primarily anaerobes
1000x more anaerobes than aerobes
There are up to 400 different bacterial species in the colon and the vast
majority (99.9%) are strict anaerobes.
Genus Log10 bacteria per gram
feces
Non-sporing anaerobes
Bacteriodes spp. 10- 11
Bifidobacterium spp. 10- 11
Eubacterium spp. 9 - 11
Propionibacterium spp. 9 - 11
Veillonella spp. 5-8

Sporing anaerobes
Clostridium spp. 5-9

Sporing aerobes
Bacillus spp.


Microaerophiles
Lactobacillus spp. 7-9
Streptococcus spp. 7-9
Enterococci 5-7
Facultative organisms
Coliforms 7-9
other Enterobacteria 5 -9
Key Properties of Probiotics
Bacteria of human origin
Safe to use in large amounts in clinical practice
Resist secretions of the upper GI tract
Survive passage through the GI tract
Adhere to human intestinal cells
Key Properties of Probiotics
Able to colonize the lumen of the GI tract
Help to protect the cells against invasion by pathogens
Produce antimicrobial substances
hydrogen peroxide
organic acids
bacteriocins
Antagonize carcinogenic and pathogenic flora
 The Big players
Lactobacillus acidophilus
Lactobacillus acidophilus is found primarily in the
small intestine
It produces natural antibiotics (lactocidin &
acidophilin), thereby, increasing the immune
system's resistance against harmful bacteria and
fungus i.e. Candida albicans, Salmonella, E. coli,
and Staphylococcus aureus
It implants itself on the intestinal walls, the lining of the
vagina, cervix and urethra
For years it was assumed that Lactobacillus acidophilus
was the most beneficial form of the good bacteria.
However, recent research has revealed that Lactobacillus
rhamnosus is just as important for good bacteria
supplementation.
Bifidobacterium bifidum
 Bifidobacterium bifidum reside mainly in the mucous
membrane of the large intestine and vaginal tract
 Digests lactose
 Produces the most beneficial form of lactic acid and acetic acid
 Ferments indigestible fibers which produces more energy
 Synthesizes some vitamins and aids mineral absorption
(calcium, magnesium and zinc)
 Inhibits the growth of Salmonella sp., Listeria, Shigella, E. coli
and Clostridium perfringens by crowding out these bad
bacteria and eating their nutrients
 Fights the harmful bacteria in the body by lowering the
intestinal pH through production of fatty acids
 Absorbs large quantities of ferrous ions, inhibiting the growth
of bad bacteria
Lactobacillus rhamnosus 
 Lactobacillus rhamnosus is a healthier species of good
bacteria and colonizes gut mucosa
 Relieves hypersensitivity reactions and intestinal
inflammation in individuals with eczema and food
allergies
 Excellent stability over a wide range of temperatures and
pH levels
 Inhibits the growth of harmful bacteria
 Enhances the immune system's resistance
 Demonstrated antitumor activity
 Prevents food allergies caused by a "leaky gut" condition
 Minor Players
Lactobacillus plantarum

Helps produce lactolin, a natural antibiotic

Synthesizes the amino acid, L-lysine, which is anti-viral

Bifidobacterium infantis
 Present in the intestines of infants and adults
 Present in the vaginal tract

Lactobacillus salivarius
 Destroys harmful bacteria
 Aids in bowel disorders

Lactobacillus bulgaricus
 Used in fermenting natural yogurt
 Produces lactic acid
 Provides a good environment for Lactobacilli and Bifidobacterium to grow
Lactobacillus casei
 Close relative to Lactobacillus acidophilus

Secretes "peptidoglycan" a recognized substance that supports the body's
natural defenses
Lactobacillus brevis
 Produces lactic acid
 Synthesizes Vitamins D & K
Streptococcus thermophilus
 Breaks down milk products by producing lactase (helps individuals that are lactose
intolerant)
 Destroys Pseudomonas sp., E. coli, Staphylococcus aureus, Salmonella sp., and
Shigella
 Produces Methanol acetone, a potent anti-pathogenic agent
Undesirable types such as E. coli, Klebsiella,
Clostridium and Candida albicans.
Mechanism
Aid in lactose digestion -Bacterial lactase hydrolyses
lactose
Resistance to enteric pathogens
Colonization resistance Secretory immune effect
Alteration of intestinal conditions to be less favorable for
pathogenicity (pH, short chain fatty acids, bacteriocins)
Alteration of toxin binding sites
Influence on gut flora populations
Adherence to intestinal mucosa, interfering with
pathogen adherence
Up regulation of intestinal mucin production, interfering
with pathogen attachment to intestinal epithelial cells
Anti-colon cancer effect
Mutagen binding
Carcinogen deactivation
Inhibition of carcinogen-producing enzymes of
colonic microbes
Immune response
Influence on secondary bile salt concentration
Small bowel bacterial overgrowth
Influence on activity of flora, decreasing toxic
overgrowth metabolite production
Alteration of intestinal conditions to be less favorable
to overgrowth of flora populations
Immune system modulation
Strengthening of non-specific defence against
infection and tumors
Adjuvant effect in antigen-specific immune responses
Enhancement of secretory IgA production
Allergy
Prevention of antigen translocation into blood stream
Blood lipids, heart disease
Assimilation of cholesterol within bacterial cell
Increased excretion of bile salts due to deconjugation
by bile salt hydrolase
Antioxidative effect
Antihypertensive effect
Peptidase action on milk protein yields tripeptides
which inhibit angiotensin 1 converting enzyme
Cell wall components act as angiotensin converting
enzyme inhibitors
Urogenital infections
Adhesion to urinary and vaginal tract cells
Colonization resistance
Inhibitor production (H2O2)
Hepatic encephalopathy -Inhibition of urease-
producing gut flora

Infection caused by Helicobacter pylori - Production

of inhibitors of H. pylori (lactic acid and others)
Immune modulation by probiotics
Microbiotic therapy
Indications for use:
Crohn's disease, ulcerative colitis
 Intestinal disturbances, gas and bloating,
constipation, diarrhea, yeast-overgrowth, irritable
bowel syndrome,
Autoimmune conditions, lupus, AIDS,
rheumatoid arthritis,
During and post antibiotic use, post
chemotherapy, post radiation
 Food allergies
• Infection with Helicobacter pylori
• Tooth decay and periodontal disease
• Vaginal infections
Diarrhoea dx and respiratory infections that children
acquire in day care
Skin infections.
 Prevent and manage atopic dermatitis (eczema) in
children.
Drawbacks
LGG Bacteremia -children with short gut-4
Bacteremia -children with central catheters -2
Endocarditis -1
Liver abscess-1
Lactobacillus rhamnosus Endocarditis-1
 B subtilis Bacteremia-5
L acidophilus Bacteremia-1
S boulardii Fungemia (including an ICU outbreak)-23
Increased mortality in probiotic group in pancreatitis
 Concern about antibiotic resistance
transfer in the GI tract between probiotics and
pathogenic bacteria
Transfer of native lactobacillus plasmids is rare
 Lactobacillus GG does not appear to have any
plasmids any plasmids
Prebiotics
Simply put they are substrates for probiotics
1-should resist host digestion and absorption in
the stomach and the small intestine

2-reach the large bowel unmodified, where it is

fermented by the microflora colonizing the
gastrointestinal system.
3-Selectively stimulate the
growth or activity of
potentially beneficial bacteria,
bifidobacteria &lactobacilli,
4-Decreasing the number
of facultative anaerobic strains
such as Escherichia coli and
Clostridia
 CHEMICAL STRUCTURE
They are oligosaccharides,
(molecules containing a small
number (three to about ten) of
monosaccharide residues
connected by glycosidic
linkages.
 MOST IMPORTANT AND
POPULAR PREBIOTICS

Fructo oligosaccharides
(FOS).
 inulin
Lactulose
Galacto oligosaccharides
(GOS).
 CHEMICAL STRUCTURE

INULIN & FOS - consist of short chains of fructose
molecules
 (GOS), which also occur naturally, consist of short chains of
galactose molecules.
INULIN
 MECHANISM OF ACTION
PREBIOTICS
LARGE BOWELS

BETA-FRUCTOSIDASE
BETA-GALACTOSIDASE
PREBIOTICS

DEGRADATION
( FERMENTATION)
LACTATE , ACETATE , BUTYRATE. SCFA .

1- DECREASE THE INTRALUMINAL PH

2- DIRECTLY INHIBITING THE GROWTH AND
ACTIVITIES OF HARMFUL MICRORGANISMS
3- CONTRIBUTING TO STIMULATION OF THE
GROWTH OF BIFIDOBACTERIA
Genestra Brands Form Seroyal
New! Oct 2004, all HMF probiotics contain a substantial increase in potency (double) and no price
increase.

 HMF Replete contains…

 Lactobacillus acidophilus
 Lactobacillus salivarius
 Bifidobacterium bifidum
 Bifidobacterium lactis

 Fructo-oligosaccharides
 high concentrations ensure
rapid establishment and
dominance of probiotic cultures
in the GI

 Indicated during and following

antibiotic therapy and
chemotherapy. 
Conclusion
Perhaps our ancestors lived long because of probiotic
Modern food processing industry destroyed that
natural protection
Revolution in modern medicine is restoring what we
lost
It is a new field of applied medicine
More studies are needed to establish their short and
long term effect.