Probiotics Clinical Uses with pharmacology

Probiotics Clinical Uses with pharmacology. Various bacteria used in gut immunity

1. Probiotics In Human Health

2. Introduction
“Let food be thy medicine & medicine be thy food.”
- Hippocrates

3. 
Probiotics – “For Life” coined by Lilly & Stillwell.
Definition – “live microorganisms which when administered in
adequate amounts confer a health benefit on the host.” by WHO.
“Prolongation of life”- by Ellie metchinkoff in1908.

“Escherichia coli Nissle 1917” isolated by Alfred Nissle.

Henry Tisser isolated Bifidobacterium from breastfed infant.
History of Probiotics

4. Prebiotics – “Non digestible food ingredient which
beneficially affects the host by selectively stimulating the growth
of &/or activating the metabolism of health promoting bacteria in
intestinal tract”

Synbiotics- “Appropriate combinations of pre- and probiotic
are synbiotics.”

5. Criteria for Probiotics
Nonpathogenic, of human origin.

Stable in acid & bile, able to adhere G.I. mucosa.

Influence human metabolic activities, modulates immune
system response & produce antimicrobial substances.

Scientifically proven beneficial physiological effect &
safety.
 retain viability during storage & technical process.

6. Strains
The most common form for probiotics are dairy products
and probiotic fortified foods.
However, tablets, capsules, powders and sachets containing
the bacteria in freeze dried form are also used.
Probiotics can be bacteria, moulds, yeast.
 Probiotics are strain specific.

8. Bifidobacterium
25% of the bacteria in adult colon & 95% 0f that in breast-fed.
Produce vitamins – B group,
Digestive enzymes- casein phosphate, lysozomes
Produce lactate – lower the Ph.

9. Lactobacillus casei GG (LGG)
Resistant to gastric acid & bile digestion.
Colonize human colon.
Antibiotic resistance is stable
Inhibit anaerobic bacteria like clostridium, bacteroids, staphylococcus
etc.
Decrease pH & O2 Concentration
Produce bacteriocins.

10. Saccharomyces boulardii.
It is a Yeast.
Resist digestion in stomach & reach in colon.
Inhibit growth of pathogenic bacteria.
Unaffected by antibiotics

11. Benefits of Probiotics

12. Diarrheas
Probiotics reduce the incidence of diarrhea episodes & facilitate
the recovery.
Reduce the rotavirus shedding.

Antimicrobial agent associated diarrhea.
AIDS associated diarrhea.
 Treatment of Travelers diarrhea/ Necrotizing enterocolitis.
Lactobacilli GG, Bifidobacterium, S.boulardii, S. thermophilus.

13. Cl.difficile associated diarrhoea
Due to antimicrobial use.
Probiotics have preventive role.
They are effective for prevention of recurrences.
 S. boulardii when given with metronidazole or vancomycin
– lower relative risk of recurrence than placebo.
routine prophylactic use need larger studies.

14. Lactose intolerance
90% of Africans, Asian & south American adults are lactase
deficient.
Consumption of dairy products causes intolerance.
Use of S. thermophilus, Lactobacilli delbruckii, in yogurt is
effective.
provide lactase enzyme
 comparative studies favours use of probiotics.

15. Inflammatory bowel disease
Ulcerative colitis & Crohns disease.
Steroids & 5-ASA are main treatment.
L.casei,& S. boulardii down regulate the release of TNF-α.
Prebiotics & probiotics when given reduces the relapse to
33% Vs 63% in placebo group.
E. coli Nissle 1917 is as effective as mesalazine in
maintaining remission

16. Urogenital infections
Definitive role in managing recurrent & chronic cases.
Lactobacilli GR1/B54/RC-14 – intravaginal insertion or perineal
implantation.
Incidence reduced by 79% & recurrence to 21% (47%).
Also useful in treatment of bacterial vaginosis & Candida
infection.

17. Mechanism of action in diarrhea & UTI
Production of inhibitory substances: H2O2, organic acids,
bacteriocins, lactic acid.
Inhibition of pathogen attachment to epithelial surface.
Competition for nutrients.
Stimulation of IgA .

 Trophic effect on intestinal mucosa- butyrate.
Inhibition of action of microbial toxin- cl.difficile

18. H. Pylori infection
Causes gastric ulcers & cancer.
Preclinical studies shown that lactobacilli inhibit the
growth, colonization, & survival of this pathogen.
Human studies – control gastric infection but can not
eradicate H. pylori.
Given with antipylori therapy it is more effective.

19. Hypercholesterolemia
Yogurt containing E. faecium lowers LDL & total cholesterol.
Reduce the ratio of LDL to HDL from 3.24 to 2.48.
Mechanism of action -It causes assimilation of cholesterol by
bacterial wall.
- deconjugation by bacterial acid
hydrolase.
- inhibit cholesterol synthesis.

20. Hypertension
Studies with human reduced by 14.1 mmHg. After 8 weeks
& diastolic BP by 6.9 mmHg.
It may be due bacterial wall components.
ACE inhibitor like peptides generated by probiotics.
L. heveticus & S. cerevisiae are used.

21. Kidney stones
Patients of oxalate stone have low levels of oxalobacter
formigenes.
Absence of this bacteria – higher oxalate concentration &
hyperoxaluria.
Bifidobacterium breve - oxalate degrading capability.

22. Cancer prevention
Probiotics decreases the exposure to chemical carcinogen by
- detoxifying ingested carcinogens.
- decreases the population of bacteria.
- inhibit growth of tumor cells.
- stimulate the immune system.
- produce metabolic substances that improve apoptosis.
-Consumption of fermented dairy product with probiotics
decrease the incidence of breast & colon cancer.
-L.casei reduce the recurrence of superficial bladder cancer.

23. Allergy
Lactobacilli GG or Bb12 improve atopic dermatitis, Eczema,
& reduce markers of inflammation.
L .rhamosus & L. reutri for 6 weeks in atopic children's
higher improvement compared to placebo.
Induction of regulatory T-cells & counter regulation of Th1
cells.
Reduced immunogenicity of potential allergens.
Production of IgA – strengthen mucus defenses.

24. Safety concerns
Pathogenic potential of Probiotics is low.
May cause infection in severely debilitated or immunsuppressed
patients.
Some Severe cases of liver abscess, lactobacillemia.
 fungemia due to S.boulardii, endocarditis with lactobacillemia,
bifidobacterium.
Risk of transfer of resistance via Probiotics.
Safety concern with enterococci as Probiotics - bacteremia & antibiotic
resistance

25. Problem with probiotics
Viability of probiotics – processing conditions.
Those strains live through the stressful acidic condition &
bile are preferred.
Viability may improved by using medium, nutrients like
prebiotics.
Storage at 4
0
C temperature
Encapsulation in artificial sesame oil for storage.

26. Prebiotics
Gibson & Roberfroid coined this term in 1995.
Commercially available as foods, dietary supplements, &
clinical therapeutics with oral & non oral delivery.
Mostly Prebiotics are Oligosaccharides.
Fructo-oligosaccharides, pyrodextrins, soy oligosaccharides.
Improves bioavailability of minerals – calcium, magnesium,
iron.
Prevention of cancer.

27. Status in India
Mainly used as animal feed, that also imported.
For human use - Sporolac ( sporolactobacilli)
 - Saccharomyces boulardii.
 -yogurt (L.bulgaricus + L. thermophilus)
 - Lactobacillus solution.
 - ViBact. (Bacillus mesentricus )
In India only sporulating lactobacillus are produced.

28. 
THANK YOU !

29. References
Suvarna V. C, Boby V.U. Probiotics in human health: a current
assessment; Current science.2005,88(11):1144-48.
Almeghaiseeb E. Probiotics: an overview. The Soudi Journal of
Gastroenterology 2007.13(3):150-52.

Sanders M.E. Probiotics. Food technology. 99,53(13):67-78.
Sharma A.K, Mohan P. Probiotics : making come back. Indian J
Pharmacol 2005;37(6):358-365.
www.usprobiotics.org.