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Vikas Kumar
Associate Professor of Pharmacology
Indian Institute of Technology (Banaras Hindu University)
Varanasi, India
Potential Clinical Applications
of
Probiotics
Probiotics - the Science
Microbial ecosystem and mucosal immunity
The intestine contains extensive microbiota (1010
bacteria cells), located mainly in the colon
The small intestine has a larger bacterial load that
consists of facultative anaerobes such as
Lactobacilli, Streptococci and Enterobacteria as
well as anaerobes such as Bifidobacterium,
Bacteroides and Clostridium at levels of 104-108
cells/gm of contents
2
The intestine is the body’s most important immune
function–related organ
60% of the body’s immune cells are present in the
intestinal mucosa
The immune system controls immune responses
against:
Dietary proteins
Prevention of food allergies
 Pathogenic microorganisms
Viruses (Rotavirus, Poliovirus)
Bacteria (Salmonella, Listeria, Clostridium etc.)
Parasites (Toxoplasma)
Contd….
3
Probiotics health effects exerted by live and viable
microorganisms
Probiotics application is independent of the site of
action and route of administration
Probiotics application include sites such as the oral
cavity, the intestine, the vagina and the skin
In case of probiotic foods, the health effect is usually
based on alteration of the gastrointestinal micro flora
and therefore based on survival during
gastrointestinal transit
Probiotics - Health Concept
4
Beneficial Effects of Probiotics
 Promote lactose digestion
 Build resistance to enteric pathogens
 Digest food and compete for nutrients with pathogens
 Produce bacteriocins to inhibit pathogens
 Modulate immune system
 Decrease blood lipids and aid in heart diseases
 Enhance intestinal barrier function
 Stimulate epithelial mucin production
 Scavenge superoxide radicals
 Compete for adhesion with pathogens
 Modify pathogen-derived toxins
5
Probiotics - Mode of Action
Tiwari et al, 2012
6
Probiotics - Clinical Applications
 Diarrhea
 Colon cancer
 Cardiovascular diseases
 Prevention of Helicobacter pylori infection
 Allergy
 Hepatic encephalopathy
 Inflammatory bowel disease (IBD)
 Irritable bowel syndrome (IBS)
 Lactose malabsorption
 Urogenital infections
7
8
Johannes, 2012
9
URL: http://fermentingsolutions.files.wordpress.com/2014/03/probiotics-benefits.png?w=361&h=356
Probiotic strains Lactobacillus reuteri, L. rhamnosus GG,
L. casei and Saccharomyces cerevisiae (boulardii)
significantly decreases the duration of diarrhea in children
Probiotics against Diarrhea
Probiotics
Oral Rehydration
Salts
Shortens the duration of
acute diarrheal illness in children
10
Modulation of gut microbiota
Production of antimicrobial substances
Competition for adhesion sites
Stimulation of mucus secretion
Modulation of immune response
Probiotics
Prevention of Diarrhea
Contd….
11
Antibiotic Associated Diarrhea
Disease Antibiotic treatment
Disturbance of
gut microbiota
Clostridium overgrowth
produces toxins
Diarrhea 12
Balance
Microbiota
Probiotics
Probiotics and Cancer
Enzymes of Gut Flora
Glycosidase
β- glucuronidase
Azoreductase
Nitroreductase
Probiotics
 Oligofructose plus two probiotic strains (L. acidophilus and
L. casei) supplementation in humans helped to decrease
levels of these gut flora enzymes
13
Binding/inactivation of mutagenic compounds
Production of anti-mutagenic compounds
Suppression of growth of pro-carcinogenic bacteria
Reduction of the absorption of carcinogens
Enhancement of immune function
Influence on bile salt concentrations
Contd….
Probiotics
Prevents Cancer Growth 14
Assimilation of cholesterol by bacterial cells
Deconjugation of bile acids by bacterial acid hydrolases
Cholesterol-binding to bacterial cell walls
Reduction of hepatic cholesterol synthesis
Redistribution of cholesterol from plasma to liver
Bacterial production of short-chain fatty acids
Probiotics
Reduction of blood cholesterol level
Probiotics and Heart Diseases
15
Production of antimicrobial substances
Stimulation of the mucus secretion
Competition for adhesion sites
Stimulation of specific and non-specific immune responses
Probiotics
Prevention of Helicobacter
pylori infection
Helicobacter pylori Infection
16
Reverse increased intestinal permeability
 Enhance gut-specific IgA responses
Promote gut barrier function
Modulation of immune response
Enhance IL-10 and cytokines production that promote
production of IgE antibodies
Probiotics
Beneficial in Allergy and
Atopic diseases
Probiotics and Allergy
17
Decrease portal blood ammonia by reduced bacterial
urease activity
Decrease portal blood pH due to less ammonia absorption
Decrease inflammation and oxidative stress due to reduced
ammonia toxins
Reduce uptake of other toxins
Probiotics
Prevention of Hepatic
Encephalopathy
Hepatic Encephalopathy
18
Inflammatory Bowel Disease
Modulation of immune response
Modulation of gut microbiota
Probiotics
Beneficial in Inflammatory
Bowel Disease
19
The probiotic strain E. coli Nissle may be equivalent to
Mesalazine in maintaining remission of ulcerative colitis
Probiotics have shown efficacy to induce and maintain
remission in children and adults with mild-to-moderate
ulcerative colitis
20
Ulcerative colitis
Reduction of intestinal gas production
Modulation of gut microbiota
Probiotics
Beneficial in Irritable Bowel
Syndrome
Irritable Bowel Syndrome
Probiotic strains Bifidobacterium Infantis in addition to
Lactobacillus reuteri may improve Colicky symptoms
within one week of treatment 21
Lactose Malabsorption
Action of bacterial β-galactosidase on lactose
Probiotics
Relief from Lactose Indigestion
Streptococcus thermophilus and L. delbrueckii subsp.
bulgaricus improve lactose digestion and reduce
symptoms related to lactose intolerance
22
Urogenital Tract Disorders
Production of antimicrobial substances
Competition for adhesion sites
Competitive exclusion of pathogens
Probiotics
Relief from Urogenital Infection
23
 Bacterial vaginosis, increases the risk of preterm labour
and infant mortality
 Probiotics decrease the risk of bacterial vaginosis and
maintain normal Lactobacilli vaginal flora
 L. rhamnosus GG and B. lactis BB12 can prevent atopic
dermatitis of newborn babies in 50% of cases, if mothers
ingest probiotics during pregnancy and newborns ingest
them during the first 6 months of life
Probiotics in Pregnancy
24
Probiotics in Skincare Products
Probiotic skincare product NUDE Skincare© was first
introduce in 2007 by NUDE Brands Ltd., UK/USA
Probiotics help balance internal digestion and also stabilize
microflora on the skin
Yogurt increases certain probiotic strains in skin that
protect skin from environmental stressors, soothes skin
and improves moisture retention
25
Future Trends and Research
The benefits of probiotics go way beyond gut health
Inflammatory cytokines
Neurotransmitter release
Useful in Depression
&
Anxiety
26
Probiotics
Probiotics
Reduces pathogenic bacteria in the nasal passages
Balances microflora in the nasal cavity
Useful in Nasal Congestion
&
sinusitis
Contd….
27
Contd….
Probiotics
Inflammatory cytokines in
skin
Microbial flora in skin
Useful in Acne,
Psoriasis, Eczema
and Dermatitis
28
Contd….
Probiotics
Development of new strains
Improves insulin sensitivity
Facilitates glucose transport
Reduces blood LDL level
Useful in Type-2 Diabetes
&
Obesity
29
Contd….
Probiotics
Production of antibiotic that
kills pathogenic microbes
Probiotic strains incorporate into
antiseptic powder and lotions
Development of oral
hygienic products
30
Conclusion
Probiotics have clearly established as an adjuvant in the
management of lactose malabsorption and acute diarrhea,
particularly acute infant diarrhea
Probiotic agents appear promising for the management of
C. difficile colitis, atopic disease, necrotizing enterocolitis
and other gut conditions, such as inflammatory bowel
disease
Further, well-designed clinical trials, involving large
numbers of patients, are mandatory to achieve definite
evidence of the preventive and curative role of probiotics in
medical practice
31
32
Thank you
for your attention !

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Clinical Application of Probiotics

  • 1. Vikas Kumar Associate Professor of Pharmacology Indian Institute of Technology (Banaras Hindu University) Varanasi, India Potential Clinical Applications of Probiotics
  • 2. Probiotics - the Science Microbial ecosystem and mucosal immunity The intestine contains extensive microbiota (1010 bacteria cells), located mainly in the colon The small intestine has a larger bacterial load that consists of facultative anaerobes such as Lactobacilli, Streptococci and Enterobacteria as well as anaerobes such as Bifidobacterium, Bacteroides and Clostridium at levels of 104-108 cells/gm of contents 2
  • 3. The intestine is the body’s most important immune function–related organ 60% of the body’s immune cells are present in the intestinal mucosa The immune system controls immune responses against: Dietary proteins Prevention of food allergies  Pathogenic microorganisms Viruses (Rotavirus, Poliovirus) Bacteria (Salmonella, Listeria, Clostridium etc.) Parasites (Toxoplasma) Contd…. 3
  • 4. Probiotics health effects exerted by live and viable microorganisms Probiotics application is independent of the site of action and route of administration Probiotics application include sites such as the oral cavity, the intestine, the vagina and the skin In case of probiotic foods, the health effect is usually based on alteration of the gastrointestinal micro flora and therefore based on survival during gastrointestinal transit Probiotics - Health Concept 4
  • 5. Beneficial Effects of Probiotics  Promote lactose digestion  Build resistance to enteric pathogens  Digest food and compete for nutrients with pathogens  Produce bacteriocins to inhibit pathogens  Modulate immune system  Decrease blood lipids and aid in heart diseases  Enhance intestinal barrier function  Stimulate epithelial mucin production  Scavenge superoxide radicals  Compete for adhesion with pathogens  Modify pathogen-derived toxins 5
  • 6. Probiotics - Mode of Action Tiwari et al, 2012 6
  • 7. Probiotics - Clinical Applications  Diarrhea  Colon cancer  Cardiovascular diseases  Prevention of Helicobacter pylori infection  Allergy  Hepatic encephalopathy  Inflammatory bowel disease (IBD)  Irritable bowel syndrome (IBS)  Lactose malabsorption  Urogenital infections 7
  • 10. Probiotic strains Lactobacillus reuteri, L. rhamnosus GG, L. casei and Saccharomyces cerevisiae (boulardii) significantly decreases the duration of diarrhea in children Probiotics against Diarrhea Probiotics Oral Rehydration Salts Shortens the duration of acute diarrheal illness in children 10
  • 11. Modulation of gut microbiota Production of antimicrobial substances Competition for adhesion sites Stimulation of mucus secretion Modulation of immune response Probiotics Prevention of Diarrhea Contd…. 11
  • 12. Antibiotic Associated Diarrhea Disease Antibiotic treatment Disturbance of gut microbiota Clostridium overgrowth produces toxins Diarrhea 12 Balance Microbiota Probiotics
  • 13. Probiotics and Cancer Enzymes of Gut Flora Glycosidase β- glucuronidase Azoreductase Nitroreductase Probiotics  Oligofructose plus two probiotic strains (L. acidophilus and L. casei) supplementation in humans helped to decrease levels of these gut flora enzymes 13
  • 14. Binding/inactivation of mutagenic compounds Production of anti-mutagenic compounds Suppression of growth of pro-carcinogenic bacteria Reduction of the absorption of carcinogens Enhancement of immune function Influence on bile salt concentrations Contd…. Probiotics Prevents Cancer Growth 14
  • 15. Assimilation of cholesterol by bacterial cells Deconjugation of bile acids by bacterial acid hydrolases Cholesterol-binding to bacterial cell walls Reduction of hepatic cholesterol synthesis Redistribution of cholesterol from plasma to liver Bacterial production of short-chain fatty acids Probiotics Reduction of blood cholesterol level Probiotics and Heart Diseases 15
  • 16. Production of antimicrobial substances Stimulation of the mucus secretion Competition for adhesion sites Stimulation of specific and non-specific immune responses Probiotics Prevention of Helicobacter pylori infection Helicobacter pylori Infection 16
  • 17. Reverse increased intestinal permeability  Enhance gut-specific IgA responses Promote gut barrier function Modulation of immune response Enhance IL-10 and cytokines production that promote production of IgE antibodies Probiotics Beneficial in Allergy and Atopic diseases Probiotics and Allergy 17
  • 18. Decrease portal blood ammonia by reduced bacterial urease activity Decrease portal blood pH due to less ammonia absorption Decrease inflammation and oxidative stress due to reduced ammonia toxins Reduce uptake of other toxins Probiotics Prevention of Hepatic Encephalopathy Hepatic Encephalopathy 18
  • 19. Inflammatory Bowel Disease Modulation of immune response Modulation of gut microbiota Probiotics Beneficial in Inflammatory Bowel Disease 19
  • 20. The probiotic strain E. coli Nissle may be equivalent to Mesalazine in maintaining remission of ulcerative colitis Probiotics have shown efficacy to induce and maintain remission in children and adults with mild-to-moderate ulcerative colitis 20 Ulcerative colitis
  • 21. Reduction of intestinal gas production Modulation of gut microbiota Probiotics Beneficial in Irritable Bowel Syndrome Irritable Bowel Syndrome Probiotic strains Bifidobacterium Infantis in addition to Lactobacillus reuteri may improve Colicky symptoms within one week of treatment 21
  • 22. Lactose Malabsorption Action of bacterial β-galactosidase on lactose Probiotics Relief from Lactose Indigestion Streptococcus thermophilus and L. delbrueckii subsp. bulgaricus improve lactose digestion and reduce symptoms related to lactose intolerance 22
  • 23. Urogenital Tract Disorders Production of antimicrobial substances Competition for adhesion sites Competitive exclusion of pathogens Probiotics Relief from Urogenital Infection 23
  • 24.  Bacterial vaginosis, increases the risk of preterm labour and infant mortality  Probiotics decrease the risk of bacterial vaginosis and maintain normal Lactobacilli vaginal flora  L. rhamnosus GG and B. lactis BB12 can prevent atopic dermatitis of newborn babies in 50% of cases, if mothers ingest probiotics during pregnancy and newborns ingest them during the first 6 months of life Probiotics in Pregnancy 24
  • 25. Probiotics in Skincare Products Probiotic skincare product NUDE Skincare© was first introduce in 2007 by NUDE Brands Ltd., UK/USA Probiotics help balance internal digestion and also stabilize microflora on the skin Yogurt increases certain probiotic strains in skin that protect skin from environmental stressors, soothes skin and improves moisture retention 25
  • 26. Future Trends and Research The benefits of probiotics go way beyond gut health Inflammatory cytokines Neurotransmitter release Useful in Depression & Anxiety 26 Probiotics
  • 27. Probiotics Reduces pathogenic bacteria in the nasal passages Balances microflora in the nasal cavity Useful in Nasal Congestion & sinusitis Contd…. 27
  • 28. Contd…. Probiotics Inflammatory cytokines in skin Microbial flora in skin Useful in Acne, Psoriasis, Eczema and Dermatitis 28
  • 29. Contd…. Probiotics Development of new strains Improves insulin sensitivity Facilitates glucose transport Reduces blood LDL level Useful in Type-2 Diabetes & Obesity 29
  • 30. Contd…. Probiotics Production of antibiotic that kills pathogenic microbes Probiotic strains incorporate into antiseptic powder and lotions Development of oral hygienic products 30
  • 31. Conclusion Probiotics have clearly established as an adjuvant in the management of lactose malabsorption and acute diarrhea, particularly acute infant diarrhea Probiotic agents appear promising for the management of C. difficile colitis, atopic disease, necrotizing enterocolitis and other gut conditions, such as inflammatory bowel disease Further, well-designed clinical trials, involving large numbers of patients, are mandatory to achieve definite evidence of the preventive and curative role of probiotics in medical practice 31
  • 32. 32 Thank you for your attention !