Prof. Dr. R.V.S.N. Sarma,MD., M.Sc (Canada), RCGP, FCGP, FIMSA,Senior Consultant Physician,Cardio-Metabolic and Chest SpecialistHonorary National Professor of Medicine (CGP)
visit: www.drsarma.inwww.youtube.com/user/drsarmaji
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Antibotics
Probiotics
Synbiotics
Prebiotics
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Potential benefits of Lactobacillus~125 yrs ago
1905: Concept of Probiotics
Starts immediately after birth Place of birth Type of Delivery Feeding: Time, Type Pre-lacteals vs Exclusive breast feed. Premature vs. Full term Sick babies
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1st Year;: > 200 bacterial species
Adult : 500-600 bacterial species
Elderly: 300 Bact. Species
Chr. Intestinal disorders
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For context – Total Cells Theirs ~ 100,000 billion. Ours ~ 10,000 billion.
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Friendly bacteria – ProbioticsUnfriendly / harmful Bacteria – Pathogens
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Staph. Aureus, albus Nose & skin
Mouth, Colon, Vagina Lactobacilus Sp, Bifidobact..
Candida albicans Mouth, Colon, Vagina
Vagina, Outer urethra E. Coli.
Haemophilus Sp. Nasophyrinx & Conjunctiva
Pseudomonas aeruginosa Colon & skin
Facultative Anaerobes Strict anaerobes
LACTOBACILLUS: BIFIDOBACTERIA: SACCHAROMYECES:
Probiotics(Friendly Bacteria)
NormaliseIntestine
Immunomodulation Metabolic effects
Suppression of PPMs
Intestinal mucosal integrity
Regulation of bowel movement
IBS
Strengthens immunity
Alleviate food allergy symptoms
Conrol of IBD
Production of vitamins; improves digestion
Lactose tolerance
Lowers cholesterol(Bile acid deconjugation
&Secretion)
Inhibit Potentially Pathogenic Microorganisms (PPMs)
Reduction in Intestinal pH ( through production of
SCFAs)
Production of bacteriocins
Competitive blocking of adhesion sites
Competition for nutrients
Most abundant Probiotic in GI Lactobacillus:
Acidophilus, Rhamnosus, GG Plantarum, Reuteri, Bulgaricus, Sporogens Casei
Action only in Small intestine
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Bifidobacteria 32 different species : Longum, Bifidum, infantis etc Most abundant probiotic next to lactobacilli Sp. in the GIT Action : Large Intestine
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Apart from the general Probiotics effect ,
Bifidobacteria helps is Glutamine synthesis
Glutamine helps in maintaining the mucosal integrity
NH3 + Glutamic acid ------------> GlutamineBifidobacteria
Saccharomyeces:
Boullardii,
Salivarium,
Thermophilus
Non colonising yeast – so needs repeated readministration
Action in large intestine
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6. Must be of human origin
3. Exert a beneficial effect on the host
1. Be nonpathogenic and nontoxic to the host
7. Contain a large number of viable cells and remain viable
during storage and use
4. Capable of surviving, colonizing and proliferating in the
gut (should not be killed by gastric juice / bile acids)
2. Be antagonistic to pathogens
5. Able to inhabit in the S & L intestine
Bifidobacteria is an Important Probiotic as it maintains the mucosal integrity
Hence Bifidobacteria supplementation is useful in conditions like Gastroenteritis where the GI mucosa is severely damaged
However, all the marketed preparation contains only 1 – 3 species of Bifidobacteria as against 32 required
Hence it is ideal to supplement with probiotic which give nutrient to Bifidobacteria so all 32 species can proliferate
• Non-digestible dietary supplements, which provide
‘’nutrition’’ for Probiotics
• Oligosaccharides (fructo-oligosaccharides or FOS),
Inulin, Lactulose, Lactitol
• Mutated Bacterial Species (Streptococcus faecalis,
Clostridium butyricum, Bacillus mesentericus)
• Advantage of Prebiotics in bacterial form : Addl.
Probiotic activity ( Intrinsic Probiotic activity)
Should promote the proliferation of beneficial bacteria (Lactiobaccillus , Bifidobacteria)
Supply nutrient to beneficial bacteria
Should escape digestion in the stomach and reach Intestine
Probiotics Prebiotics
Nature of the Prep
Microorganism Food supplement (eg: FOS) or Microorganism (eg : S.F )
Prime Fn To kill harmful pathogen
To supply nutrition(Killing the pathogen is an additional effect)
FOS – Recommended daily dose is 2 - 6 gm
Marketed prep. offer 100, 250 mg of FOS – Which is inadequate dose
Also at high dose , FOS cause flatulence and GI discomfort
Hence using a live mutated bacteria is beneficial as it would ensure the continuous colony count (nutrient) with out any side effect
1. Infective diarrhea (viral, bacterial)
2. Antibiotic associated diarrhea
3. Lactose intolerance
4. Recurrent aphthous ulcers and stomatitis
6. Inflammatory IBD (Ulcerative colitis, Crohn’s)
7. Irritable bowel syndrome
5. Travelers’ diarrhea
9. Pouchitis
8. Post operative state
10. Diverticular disease of colon
Due to bacteria, Virus or Protozoa
Viral diarrhoea : Rotavirus Mx : ORS / Infusion
Bacterial Diarrhoea : E.coli , Salmonella , Shigella , V. Cholerae Mx : Antibacerial
Protozoal Diarrhoea : E.Histolytics Mx : Metrinadozole
An all the 3 types , there is a disturbance of the Intestinal microflora. Hence supplementation with Bifilac normalises the gut flora by displacing the PPMs and hence reduce the duration of diarrhoea
BacteriocinBacteriocin
Bioactive peptidesBioactive peptides
Short chain fatty acidsShort chain fatty acids
Neutralization of
dietary carcinogens
Neutralization of
dietary carcinogens
Free amino acidsFree amino acids
Organic acidsOrganic acids
β-Galactosidase activityβ-Galactosidase activity
OligosaccharidesOligosaccharides
Cholesterol assimilationCholesterol assimilation
Survival and adhesion
competitions with
pathogenic bacteria
Survival and adhesion
competitions with
pathogenic bacteria
AntioxidantAntioxidant
ImmunostimulatoryImmunostimulatoryProbioticsProbiotics
LAPC
IgA
Tumors
Th0
Th1
B
IL-2 ↑
IFN- γ ↑
Th2
Antibody mediated response
Cell mediated response
Viruses
TGF-β↓IL-4 ↓IL-10 ↓
+
IL-2 ↑
IFN-γ ↑
TNF-α ↑
IFN-α ↑
Natural killer cells ↑
Macrophages ↑
Cytotoxic T-lymphocytes ↑
LL
L
Immune Response
MIntestinal Epithelium
Microorganisms
BIgG ↑
IgM ↑
IgE ↓
Non-adhesive Adhesive
M = M cells of intestinal epithelium
L = Lymphocytes
APC = Antigen presenting cells
Th = T-helper cells
IL = Interleukines
TGF = Tumour growth factor
IFN = Interferon
TNF = Tumour necrosis factor
Ig = Immunoglobulin
Protection of intestinal epithelial barrier function
Regulation of intestinal epithelial homeostasis
Regulation of intestinal microbial environment
Modifications to commensal and probiotic bacteria to enhance diarrhea prevention
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Most common antibiotics that cause diarrhea
Alteration in composition of normal intestinal bacterial micro
flora by antibiotic makes the GI tract susceptible to infection
by fungus (Candida) or bacteria, Clostridium difficile
Fungus alters absorptive surface of GI tract – diarrhea
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Pseudomembranous ColitisVolcano lesions in AAD
•Relative risk of diarrhea reduced by 40 %. By LGG / Saccharomyces•5-10 billion viable organisms X 3-4 times/day•Probiotics to be separated from Antibiotics by couple of Hours
• The incidence of AAD can go up to 26% of
patients on antibiotics,
• Broad-spectrum antibiotics are associated
with the highest rate of AAD because of
their disruptive impact on the normal
intestinal flora.
(2006) 3, 606-607
Diarrhea is a common adverse effect of antibiotic
treatments.
Antibiotic associated diarrhea occurs in about 5-30%
of patients
Almost all antibiotics, particularly those that act on
anaerobes, can cause diarrhea, but the risk is higher with
aminopenicillins, a combination of aminopenicillins and
clavulanate, cephalosporin's, and clindamycin.
BMJ 2002;324:1345-1346 (8 JUNE)
International Microbiology 2004 ; Mar 7(1) 59-62
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Lactase digests lactose commonly present in milk and milk products.
Lactose is not digested when there is a deficiency in lactase and results in diarrhea.
Supplementation with probiotics has been shown to mitigate the symptoms of lactose intolerance.
Superficial ulcers or fissures in mucosa of mouth.
Painful condition.
Each episode lasts 8 -14 days.
Exact etiology not known.
Stress appears to play a role.
Mx : B complex / multivitamin, probiotics and antiseptic or tetracycline mouth wash.
Affects tourists traveling ; Shigella
Transmission of infection:
Feco-oral route / fingers and flies.
Travelers’ diarrhea can be prevented by regular prophylactic intake of beneficial bacteria
One week before travel, during travel, one week after completion of travel.
Chronic medical condition characterized by
abdominal pain, discomfort and results in change
in the bowel frequency & consistency in the stools
Cause : Alteration in the bowel motility & transit (
due to anxiety)
Symptoms : Bloating , gas , dyspepsia ,
constipation, diarrhea , diarrhea alternating with
constipation, dysentery
Inflammation in GI Tract
Crohn’s Disease
Small & Large intestine
Ulcerative Colitis
Large intestine (Rectum & Colon)
Ulcerative colitisCrohn’s disease
Symptom : Diarrhoea / Dysentery / fever / Wt.loss
Rx : Sulphasalazine , Steroids , Immuno-suppresants
Rationale for Probiotic : IBD patients have a
compromised bowel flora due to inflammation.
Supplementation with probiotic helps to normalize
the bowel flora and there by reduces the
inflammation
Probiotics promotes the antigen specific IgA immune
response and shortens the diarrheal phase .
Also reduces the relapse rate
Inflammation of an internal pouch created in patients who
have part of their colon removed to treat ulcerative colitis
Why Probiotics : Low levels of bacterial flora in intestine
Diverticula - Formation of small bulges / bags in the colon
Diverticulitis – Inflammation/ Infection in the diverticula
Mixture of Pre and Probiotic
Probiotics – Helps in reducing the PPMs
Prebiotics – Helps in Providing food for Probiotics
Lactobacillus sporogenes 50 million
( Probiotic)
Streptococcus faecalis T-110 30 million
( Prebiotic)
Clostridium butyricum TO-A 2 million
( Prebiotic)
Bacillus mesentericus TO-A 1 million
( Prebiotic)
Streptococcus faecalis T-110 30 million
( Prebiotic)
Clostridium butyricum TO-A 2 million
( Prebiotic)
Bacillus mesentericus TO-A 1 million
( Prebiotic)
On ingestion, 3 mutated
live bacteria continue to
proliferate in the GI tract
by a process of
Symbiosis
Symbiosis : Biological
association of two or
more species to their
mutual benefit.
