use and scope of preprobiotics in various diseases. it also includes the basic mechanism by which probiotics would contribute to disease prevention as well as cure. this presentation would provide the basic idea about the history, mechanism and the role of synbiotic therapy in various diseases.

1. Pre - Probiotics

2. Definition
Probiotic
WHO:
Live microorganisms which when
administered in adequate amounts,
confer a health benefit to the host.

3. Ideal Probiotics
Ideal
Probiotic
Survives the
stomach acid
and bile
Adheres to
intestinal
lining
Imparts
health
benefits
Maintains
good viability
Non
pathogenic
and non toxic
Stability
during
processing
and storage

4. Definition
Prebiotic
• A non-digestible component which
beneficially affects the host by
selectively stimulating the growth
and/or activity of one or a limited
number of colonic bacteria.
• Examples- insulin, garlic, onions,
chicory root, Asparagus, whole
wheat, rye, barley

5. Characteristics of Prebiotics
• Should not be hydrolysed or absorbed in the upper GI
• Should be able to alter the colonic microflora towards a healthier composition or
selectively stimulates the growth of intestinal bacteria associated with health and
well being.
• Should help increase the absorption of certain minerals such as calcium and
magnesium.
• Favourable effect on the immune system and provide improved resistance
against infection.

6. Definition
Synbiotic
• PROBIOTICS + PREBIOTICS
• Foods containing the combination
of probiotics and prebiotics are
referred to as Synbiotics.

7. History
• Elie Metchnikoff
• Russian noble prize winner and
father of modern immunology
• First conceptualize “probiotics”

8. History
• In early 1930’s, Minoru shirota
developed a fermented milk
product called Yakult (probiotic
yogurt) in Japan
• Probiotic term coined in 1965 by
Lilly and Stillwell.

9. Mechanism of Action
Enhancement
of epithelial
barrier
Increased
adhesion to
intestinal
mucosa
Competitive
exclusion of
pathogens
Production
of
antimicrobial
substances
Ann Nutr Metab 2012;61:160–174
Modulation
of Immune
System

10. Enhancement of epithelial barrier
• Modulates the regulation of
several genes encoding
adherence junction proteins, such
as E-cadherin and β-catenin.
• Probiotics may initiate repair of
the barrier function after damage.
• Prevents cytokine-induced
epithelial damage
• Probiotics may promote mucous
secretion
Ann Nutr Metab 2012;61:160–174

11. Increased adhesion to intestinal mucosa
• Increase the synthesis of cell surface mucins and to modulate mucin gene
expression for the adhesion of bacterial cells to the intestinal epithelium
• Probiotics also cause qualitative alterations in intestinal mucins that prevent
pathogen binding
• Probiotic strains can also induce the release of defensins from epithelial cells
which stabilize the gut barrier function
Ann Nutr Metab 2012;61:160–174

12. Competitive exclusion of pathogens
• Creation of a hostile microecology
• Elimination of available bacterial receptor sites
• Production and secretion of antimicrobial substances and selective metabolites
• Competitive depletion of essential nutrients
Ann Nutr Metab 2012;61:160–174

13. Production of antimicrobial substances
• Probiotics induce the formation of LMW
compounds (<1,000 Da), such as organic acids,
and the production of antibacterial substances
termed bacteriocins (>1,000 Da).
• Organic acids, in particular acetic acid and
lactic acid, have a strong inhibitory effect
against Gram-negative bacteria
Ann Nutr Metab 2012;61:160–174

14. Production of antimicrobial substances
• Intestinal bacteria also produce a diverse array of health-promoting fatty
acids like conjugated linoleic acid
• Probiotic bacteria are able to produce so-called de-conjugated bile acids
which are said to be having strong anti microbial activities.
• Probiotics also produce antifungal substances, such as benzoic acid,
methylhydantoin, mevalonolactone and short-chain fatty acids.
Ann Nutr Metab 2012;61:160–174

15. Modulation of Immune system
• Probiotics have the ability to interact with epithelial and dendritic cells (DCs)
and with monocytes/macrophages and lymphocytes1
• Probiotics induce the production and expression of T helper 1 type cytokines,
TNFα, IL 2, IL 1β, IL6 and IL18 in the peripheral blood mononuclear cells.2
• Probiotics modulate the host immunity by characterization of the host families
of pattern-recognition molecules, such as TLR and NOD-like receptors, as well
as modulating key signaling pathways, such as NF- ĸB and MAPK.1
1Ann Nutr Metab 2012;61:160–174, 2Expert Rev Anti Infect Ther. 2006 Apr;4(2):261-75.

16. Various probiotic strains
• Lactobacillus species
• L. acidophilus
• L. plantarum
• L. casei subspecies rhamnosus
• L. brevis
• L. delbreuckii subspecies bulgaricus
• Bifidobacterium species
• B. adolescentis
• B. bifidum
• B. longum
• B. infantis
• B. breve
• Others
• Saccharomyces boulardii
• Streptococcus salivarius ssp.
thermophilus
• Lactococcus lactis ssp. lactis
• Lactococcus lactis s ssp. cremoris
• Enterococcus faecium
• Leuconostoc mesenteroides ssp.
dextranicum
• Propionibacterium freudenreichii
• Pediococcus acidilactici

17. Role in Various Diseases
• Antibiotic Associated Diarrhea
• Travelers' Diarrhea
• Acute Diarrhea in Children
• Irritable Bowel Syndrome
• Inflammatory Bowel Diseases
• Lactose Intolerance
• C Difficile associated diarrhea
• Necrotizing enterocolitis
• Allergies
• Rheumatoid arthritis
• Cancer
• Dental Caries

18. Antibiotic Associated Diarrhea
• Lactobacillus1 and Enterococcus2 as a probiotic
were found to be overall reducing the risk of
antibiotic associated diarrhea.
• Using probiotics for the prevention of antibiotic-
associated diarrhea reduces the risk of AAD by
51%3
• L. Rhamnosus GG followed by S. Boulardii were
found to be most effective strains for the
condition3
1Aliment. Pharmacol. Ther. 16(8), 1461-1467 (2002) 2Br. Med. J. 324(7350).1361 (2002) 3Antibiotics (Basel). 2017 Dec; 6(4): 21.

19. Traveler’ Diarrhea
• Diarrhea on travel, why?
• Travelers to underdeveloped
countries face high incidence of
diarrhea: 30 – 50% or more
• In a study, LGG strain was found
to be reducing the risk of
diarrhea up to 40% after the 1st
week.
• It provided a protection rate
against diarrhea of 47%
Expert Rev Anti Infect Ther. 2006 Apr;4(2):261-75

20. Travelers’ Diarrhea
• Another study evaluated L. Acidophilus vs L. fermentum vs Placebo,
which did not find significant results.
• A large Finnish study, evaluated the effects of probiotics in two
groups. One of which showed significant reduction in incidence of
diarrhea after taking probiotics and the other didn’t.
• Thus, the role of probiotics in Travelers’ diarrhea is conflicting.
Expert Rev Anti Infect Ther. 2006 Apr;4(2):261-75

21. Acute Diarrhea in Children
• Childhood diarrhea is very common in the world and in
developing countries, it is twice as common
• Various probiotic species like Lactobacillus, S.
Thermophilus, Enterococcus SF68 and Bifidobacterium
were found to be shortening the duration of diarrheal
illness.
Expert Rev Anti Infect Ther. 2006 Apr;4(2):261-75

22. Acute Diarrhea in Children
• A study by European Society for Pediatric Gastroenterology, Hepatology &
Nutrition (ESPGHAN) concluded that Patients receiving LGG had a shorter
duration and decreased severity of illness and shorter hospital stay.
• Another study using L. reuteri also concluded on conferring the similar
results.
• In conclusion, there is convincing evidence from may studies and a large
number of subjects that probiotics are effective in the treatment of acute
diarrhea, particularly in children.
Expert Rev Anti Infect Ther. 2006 Apr;4(2):261-75

23. Irritable Bowel Syndrome
• IBS is a common disease characterized by abdominal
pain and altered bowel function.
• There is strong evidence for a relationship between
commensal bacteria and intestinal health.
• The studies evaluating the role of Probiotics in IBS
showed mixed results
Expert Rev Anti Infect Ther. 2006 Apr;4(2):261-75

24. Irritable Bowel Syndrome
• Those studies showing positive results, were
associated with
• Improvement in abdominal pain
• Decreased daily bowel movements
• Decreased bloating
• Overall symptom reduction
Expert Rev Anti Infect Ther. 2006 Apr;4(2):261-75

25. Inflammatory Bowel Diseases
• IBD has been said to be affected by
dysbiosis in the bowel and dysregulation
of the immune system leading to
inflammation of GIT.
• Probiotics have been studied for
treatment of symptoms of IBD as well as
for maintaining remission and preventing
relapses specifically pouchitis.
Expert Rev Anti Infect Ther. 2006 Apr;4(2):261-75

26. Inflammatory Bowel Diseases
• Studies have shown conflicting results of use of probiotics in IBD
• Studies using L. Acidophilus, B. Lactis, VSL #3 were found to be
effective in decreasing clinical symptoms, relapse rate and histological
inflammation in patients of pouchitis.
• Study using B. Breve, B. Bifidum and L acidophilus significantly
decreased the rate of relapse in patients of UC.
Expert Rev Anti Infect Ther. 2006 Apr;4(2):261-75

27. Lactose Intolerance
• Use of probiotics in LI has been evaluated
using different strains like Bifidobacterium,
S. Boulardii, Lactobacillus and combination.1
• B. longum and B. animalis reduces lactose
intolerance by increasing production of the
enzyme ß-galactosidas.2
1Crit Rev Food Sci Nutr. 2018 Feb 9:1-9, 2Journal of Dairy Science 79 (5):750–757

28. Lactose Intolerance
• S. boulardii significantly shortens the
duration of diarrhea and allows quicker
weight regain than a standard formula.1
• Probiotic therapy has been associated with2
• Overall decrease in symptoms like
• Nausea
• Vomiting
• Abdominal pain
• Improvement in breath hydrogen test,
1Archives De Pediatrie 17 (5):459–465, 2Crit Rev Food Sci Nutr. 2018 Feb 9:1-9

29. C. Difficile Associated Diarrhea
• Mainly associated with altered
microflora after antibiotic usage.
• In a study done by Bennett, LGG
conferred overall cure rate of 94% in
C. Difficile associated diarrhea.1
• Lactobacillus and Bifidobacterium
were found to be non significantly
effective in the disease.2
1Nutr. Today 31(6), 35S-38S (1996), 2Int. Microbiol. 7(1), 59-62 (2004)

30. Necrotizing Enterocolitis
• Occurs in large population of very low birth
weight premature infants1
• A study used L. Acidophilus and B. Infantis
as a probiotic in 367 VLBW infants.2
• Probiotics were found to be decreasing the
incidence of death, necrotizing enterocolits
and culture proven sepsis.2
1Expert Rev Anti Infect Ther. 2006 Apr;4(2):261-75, 2Pediatrics 115(1), 1-4 (2005)

31. Others
• LGG has been shown to be effective in prevention as well as
treatment of allergy manifestations.1
• B. Lactis significantly improved skin condition in patients of
atopic eczema.1
• In preclinical studies, LGG significantly improved experimental
arthritis.2
• In an RCT, LGG was found to be decreasing number of
swollen joints and overall RA activity statistically
insignificantly.3
1Clin. Exp. Allergy 30(1),1604 – 1610 (2000), 2J Nutr 134(8), 1964-1969 (2004), 3Scand J Rheumatol 32(4),211-215 (2003)

32. Others
• In preclinical studies, probiotics are found to be
having anticarcinogenic properties by preventing
toxin induced DNA damage.1
• Amongst various probiotics tested, LGG and
Bifidobacterium were found to be most beneficial.2
• Several case control studies have suggested an
inverse association between yogurt consumption and
risk of colon cancer.3
1Nutr Cancer 26(3),365-380 (1996), 2Nutr Cancer 51(1),102-109(2005), 3Expert Rev Anti Infect Ther. 2006 Apr;4(2):261-75

33. Others
• Activity of LGG against Streptococcus spp. is
thought to be the major reason for effectiveness of
probiotics in dental caries.1
• In a study, probiotic milk was found to be having
significantly beneficial effects on the clinical
development of dental caries.2
• The viable counts of S mutans were significantly
reduced in the mouths of children of probiotic
group.1
1Expert Rev Anti Infect Ther. 2006 Apr;4(2):261-75, 2Caries Res 35(6), 412-420 (2001)

34. Safety
• Most of the probiotic use are found to be safe
• Care should be taken in severely ill or immune-compromised
patients
• Most common side effects
• Constipation
• Flatulence
• Hiccups
• Nausea
• Infection
• Lactobacillus bacteremia, D-lactic acidosis and liver abscess
formation have been observed rarely.
Clin Infect Dis 46, S104–S111, discussion S144–S151

35. Conclusion
• Probiotics have opened new doors in the field of GI ailments treatments.
• During various trials and study, the safety of the probiotics has been
established and thus if administered with care, it is devoid of any major
devastating side effects.
• In many of the GI diseases, pre probiotics have been found to be effective.
• In some other diseases, though some positive results are found, further
definitive trials are recommended.

36. THANK YOU