pro bio tics in pediatric practice

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APEPEOKHA

June 04,2010


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outliney Introductiony Historical perspectivey Definitiony Normal intestinal micro ecologyy Typesy Key properties of probioticsy Mechanismy

Usesy Drawbacksy Prebioticsy Conclusion


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Introductiony The concept of probiotics evolved at the turn of the

20th century from a hypothesis first proposed by

Nobel Prize winning Russian scientist ElieMetchnikoff (Bibel, 1988)

y He suggested that the long, healthy life of Bulgarianpeasants resulted from their consumption of

fermented milk products.y He believed that when consumed, the fermenting

bacillus (Lactobacillus) positively influenced themicroflora of the colon.


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y Modern civilisation is faced with a progressive increasein immune-mediated gut-related health problems

such as allergies, autoimmune and inammatorydiseases.

y Microbial stimulation is required for the maturation ofthe immune system to ght allergic disease.

yThe human diet once contained several thousandtimes more bacteria than it does today


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y Industrial processing has led to extensive

pasteurisation and sterilisation.y Probiotics provide a safe microbial stimulus for the

maturation of the gut-associated lymphoid tissue.


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A Brief History of Probioticsy Metchnikoff 1907 ingesting yogurt with

Lactobacilli reduces toxic bacteria of the gut andprolongs life

y Kipeloff 1926 stressed importance of Lactobacillusacidophilus for good health

y Rettger 1930s early clinical application ofLactobacillus

y Parker 1974 1st to use the term probioticsy Fuller 1989 defined probiotics


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Definitiony Probiotics are defined as live microbial food ingredients

that have a beneficial effect on human health (Salminen etal., 1998).

y prebioticsnon digestible food ingredients that selectivelystimulate the growth and activity of beneficialmicroorganisms already in peoples colons. In common

terms, prebiotics are food for bacterial species that areconsidered benecial for health and well-being.

y When probiotics and prebiotics are mixed together, theyform a synbiotic.


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Intestinal Flora: A symbiotic relationship

with the host

y Human GI tract contains 10x more bacteria (1014)than eukaryotic cells in the body

y

Protects the hosty Stimulates immune function

y Produces antimicrobial substances

y Trophic effect on intestinal epithelium

y Maintains the enterohepatic circulation of bileacids

y Involved in metabolic processes (i.e.,fermentation) in the colon


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Intestinal Microflora: Location & Prevalence

y Rare in the esophagus

y Uncommon in the stomach

y primarily gram (+)y 102 - 104

y 105 in the jejunum primarily aerobes

y 1010 1012 in the colon

y primarily anaerobes

y 1000x more anaerobes than aerobes


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There are up to 400 different bacterial species in the colon and the vast

majority (99.9%) are strict anaerobes.

Genus Log10 bacteriaper gram fecesy Non-sporing anaerobes

y Bacteriodes spp. 10- 11y Bifidobacterium spp. 10- 11

y Eubacterium spp. 9 - 11y Propionibacterium spp. 9 - 11y Veillonella spp. 5 - 8

y Sporing anaerobesy Clostridium spp. 5 - 9

y Sporing aerobesy Bacillus spp.


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y Microaerophiles

yLactobacillus spp. 7 - 9

yStreptococcus spp. 7 - 9yEnterococci 5 - 7

y Facultative organisms

yColiforms 7 - 9yother Enterobacteria 5 -9


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Key Properties of Probioticsy Bacteria of human origin

y Safe to use in large amounts in clinical practice

y Resist secretions of the upper GI tracty Survive passage through the GI tract

yAdhere to human intestinal cells


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Key Properties of ProbioticsyAble to colonize the lumen of the GI tract

y Help to protect the cells against invasion by pathogens

y Produce antimicrobial substancesy hydrogen peroxide

y organic acids

y bacteriocins

yAntagonize carcinogenic and pathogenic flora


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The Big playersyLactobacillus acidophilusy Lactobacillus acidophilus is found primarily in the

small intestiney

It produces natural antibiotics (lactocidin &acidophilin), thereby, increasing the immunesystem's resistance against harmful bacteria andfungus i.e. Candida albicans, Salmonella, E. coli,and Staphylococcus aureusy

It implants itself on the intestinal walls, the lining of thevagina, cervix and urethray For years it was assumed that Lactobacillus acidophilus

was the most beneficial form of the good bacteria.However, recent research has revealed that Lactobacillusrhamnosus is just as important for good bacteriasupplementation.


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yBifidobacterium bifidum

y Bifidobacterium bifidum reside mainly in the mucousmembrane of the large intestine and vaginal tract

y Digests lactosey Produces the most beneficial form of lactic acid and acetic acidy Ferments indigestible fibers which produces more energyy Synthesizes some vitamins and aids mineral absorption

(calcium, magnesium and zinc)y

Inhibits the growth ofSalmonella sp., Listeria, Shigella, E. coliand Clostridium perfringens by crowding out these badbacteria and eating their nutrients

y Fights the harmful bacteria in the body by lowering theintestinal pH through production of fatty acids

y Absorbs large quantities of ferrous ions, inhibiting the growthof bad bacteria


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yLactobacillus rhamnosusy Lactobacillus rhamnosus is a healthier species of good

bacteria and colonizes gut mucosay Relieves hypersensitivity reactions and intestinal

inflammation in individuals with eczema and foodallergies

y Excellent stability over a wide range of temperatures andpH levels

y Inhibits the growth of harmful bacteriay Enhances the immune system's resistancey Demonstrated antitumor activityy Prevents food allergies caused by a "leaky gut" condition


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Minor Players

y Lactobacillus plantarumy Helps produce lactolin, a natural antibioticy Synthesizes the amino acid, L-lysine,which is anti-viral

y

Bifidobacterium infantisy Present in the intestines of infants and adultsy Present in the vaginal tract

y Lactobacillus salivariusy Destroys harmful bacteriay

Aids in bowel disorders

y Lactobacillus bulgaricusy Used in fermenting natural yogurty Produces lactic acidy Provides a good environment for Lactobacilli and Bifidobacterium to grow


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y Lactobacillus caseiy Close relative to Lactobacillus acidophilus

y Secretes "peptidoglycan" a recognized substance that supports the body'snatural defenses

y Lactobacillus brevisy Produces lactic acidy Synthesizes Vitamins D & K

y Streptococcus thermophilusy Breaks down milk products by producing lactase (helps individuals that are lactose

intolerant)y Destroys Pseudomonas sp., E. coli, Staphylococcus aureus, Salmonella sp., and

Shigellay ProducesMethanol acetone, a potent anti-pathogenic agent

y Undesirable types such as E. coli, Klebsiella,Clostridium and Candida albicans.


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MechanismyAid in lactose digestion -Bacterial lactase hydrolyses

lactose


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Resistance to enteric pathogensy Colonization resistance Secretory immune effect

y Alteration of intestinal conditions to be less favorable for

pathogenicity (pH, short chain fatty acids, bacteriocins)y Alteration of toxin binding sites

y Influence on gut flora populations

y Adherence to intestinal mucosa, interfering with pathogen

adherencey Up regulation of intestinal mucin production, interfering

with pathogen attachment to intestinal epithelial cells


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Anti-colon cancer effecty Mutagen binding

y Carcinogen deactivation

y Inhibition of carcinogen-producing enzymes ofcolonic microbes

y Immune response

y Influence on secondary bile salt concentration


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Small bowel bacterial overgrowthy Influence on activity of flora, decreasing toxic

overgrowth metabolite production

y

Alteration of intestinal conditions to be less favorableto overgrowth of flora populations


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Immune system modulationy Strengthening of non-specific defence against

infection and tumors

y

Adjuvant effect in antigen-specific immune responsesy Enhancement of secretoryIgA production


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Allergyy Prevention of antigen translocation into blood stream


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Blood lipids, heart diseaseyAssimilation of cholesterol within bacterial cell

y Increased excretion of bile salts due to deconjugation

by bile salt hydrolaseyAntioxidative effect


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Antihypertensive effecty Peptidase action on milk protein yields tripeptides

which inhibit angiotensin 1 converting enzyme

y

Cell wall components act as angiotensin convertingenzyme inhibitors


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Urogenital infectionsyAdhesion to urinary and vaginal tract cells

y Colonization resistance

y Inhibitor production (H2O2)


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Immune modulation by probiotics


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Microbiotic therapyy Indications for use:

y Crohn's disease, ulcerative colitis

yIntestinal disturbances, gas and bloating,constipation, diarrhea, yeast-overgrowth,irritable bowel syndrome,

yAutoimmune conditions, lupus, AIDS,

rheumatoid arthritis,y During and post antibiotic use, post

chemotherapy, post radiation

y Food allergies


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Infection with Helicobacter pylori

Tooth decay and periodontal disease

Vaginal infectionsy Diarrhoea dx and respiratory infections that children

acquire in day care

y Skin infections.

y Prevent and manage atopic dermatitis (eczema) inchildren.


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Drawbacksy LGG Bacteremia -children with short gut-4

y Bacteremia -children with central catheters -2

y Endocarditis -1y Liver abscess-1


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y Lactobacillus rhamnosus Endocarditis-1

y B subtilis Bacteremia-5

y L acidophilus Bacteremia-1y S boulardii Fungemia (including an ICU outbreak)-23

y Increased mortality in probiotic group in pancreatitis


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y Concern about antibiotic resistance

y transfer in the GI tract between probiotics and

pathogenic bacteriay Transfer of native lactobacillus plasmids is rare

y Lactobacillus GG does not appear to have anyplasmids any plasmids


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Prebioticsy Simply put they are substrates for probiotics


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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.


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3-Selectively stimulate thegrowth or activityofpotentially beneficial bacteria,

bifidobacteria &lactobacilli,4-Decreasing the number

of facultative anaerobic strainssuch as Escherichia coli andClostridia


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They are oligosaccharides,(molecules containing a small

number (three to about ten) ofmonosaccharide residues

connected byglycosidiclinkages.


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MOST IMPORTANT AND

POPULAR PREBIOTICS

yFructo oligosaccharides(FOS).y inulinyLactuloseyGalacto oligosaccharides(GOS).


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CHEMICAL STRUCTURE

y INULIN & FOS - consist of short chains offructose

molecules

y (GOS),which also occur naturally, consist of short chains of

galactose molecules.INULIN


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LARGEBOWELS

BETA-FRUCTOSIDASEBETA-GALACTOSIDASE

PREBIOTICS

DEGRADATION( FERMENTATION)

LACTATE , ACETATE , BUTYRATE. SCFA .

1- DECREASE THE INTRALUMINAL PH

2- DIRECTLY INHIBITING THE GROWTH ANDACTIVITIESOFHARMFULMICRORGANISMS3- CONTRIBUTING TOSTIMULATIONOF THE

GROWTHOFBIFIDOBACTERIA


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Genestra Brands Form SeroyalNew! Oct 2004, all HMF probiotics contain a substantial increase in potency (double) and no price

increase.

y HMF Replete containsy Lactobacillus acidophilusy Lactobacillus salivariusy Bifidobacterium bifidumy Bifidobacterium lactis

y Fructo-oligosaccharidesy high concentrations ensure

rapid establishment anddominance of probiotic cultures

in the GI

y Indicated during and followingantibiotic therapy andchemotherapy.


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Conclusiony Perhaps our ancestors lived long because of probiotic

y Modern food processing industry destroyed that

natural protectiony Revolution in modern medicine is restoring what we

lost

y It is a new field of applied medicine

y More studies are needed to establish their short andlong term effect.


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pro bio tics in pediatric practice

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