Transcript Probiotics by Dr Sarma
PREBIOTICS AND PROBIOTICS
Prof. Dr. R.V.S.N. Sarma, MD., M.Sc (Canada), RCGP, FCGP, FIMSA, Senior Consultant Physician, Cardio-Metabolic and Chest Specialist Honorary National Professor of Medicine (CGP)
visit: www.drsarma.in
www.youtube.com/user/drsarmaji
Antibotics Probiotics Prebiotics Synbiotics
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LOUIS PASTEUR (1822 - 1895) METCHNIKOFF ELIE (1848-1916)
Potential benefits of Lactobacillus~125 yrs ago 1905: Concept of Probiotics 3
COLONIZATION OF GUT
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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COLONIZATION OF GUT 1 st Year;: > 200 bacterial species Adult : 500-600 bacterial species Elderly: 300 Bact. Species Chr. Intestinal disorders
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RELATIVE PROPORTION
For context – Total Cells
Theirs ~ 100,000 billion.
Ours ~ 10,000 billion.
GUT FLORA IN BREAST FED VS FORMULA FED BABIES
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Friendly bacteria Unfriendly / harmful Bacteria – Probiotics – Pathogens
COMMON FLORA
Facultative Anaerobes Staph. Aureus, albus Mouth, Colon, Vagina Candida albicans Vagina, Outer urethra Haemophilus Sp. Pseudomonas aeruginosa Strict anaerobes Nose & skin Lactobacilus Sp, Bifidobact.. Mouth, Colon, Vagina E. Coli. Nasophyrinx & Conjunctiva Colon & skin LACTOBACILLUS: BIFIDOBACTERIA: SACCHAROMYECES: 9
PROBIOTICS ( “FOR LIFE’’)
Probiotics (Friendly Bacteria) Normalise Intestine Suppression of PPMs Intestinal mucosal integrity Regulation of bowel movement IBS Immunomodulation Strengthens immunity Alleviate food allergy symptoms Conrol of IBD Metabolic effects Production of vitamins; improves digestion Lactose tolerance Lowers cholesterol (Bile acid deconjugation &Secretion)
MECHANISM OF ACTION Inhibit Potentially Pathogenic Microorganisms (PPMs) Reduction in Intestinal pH ( through production of SCFAs) Production of bacteriocins Competitive blocking of adhesion sites Competition for nutrients
MOA OF PROBIOTICS
TYPES OF PROBIOTICS
Most abundant Probiotic in GI Lactobacillus:
Acidophilus,
Rhamnosus, GG
Plantarum,
Reuteri,
Bulgaricus,
Sporogens
Casei Action only in Small intestine 14
TYPES OF PROBIOTICS
Bifidobacteria
32 different species : Longum, Bifidum, infantis etc
Most abundant probiotic next to lactobacilli Sp. in the GIT
Action : Large Intestine 15
UNIQUENESS OF BIFIDOBACTERIA
Apart from the general Probiotics effect , Bifidobacteria helps is Glutamine synthesis Glutamine helps in maintaining the mucosal integrity NH3 + Glutamic acid ------------> Glutamine Bifidobacteria
TYPES OF PROBIOTICS SACCHAROMYCES BOULARDII
Saccharomyeces:
Boullardii,
Salivarium,
Thermophilus
Non colonising yeast – so needs repeated readministration
Action in large intestine 17
IDEAL PROPERTIES OF A PROBIOTIC
1. Be nonpathogenic and nontoxic to the host 2. Be antagonistic to pathogens 3. Exert a beneficial effect on the host 4.
Capable of surviving, colonizing and proliferating in the gut (should not be killed by gastric juice / bile acids) 5. Able to inhabit in the S & L intestine 6. Must be of human origin 7. Contain a large number of viable cells and remain viable during storage and use
IS PROBIOTIC PREPN WITH BIFIDOBACTERIA USEFUL ?
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
PREBIOTICS
• 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)
PREBIOTICS – IDEAL CHARACTERS
Supply nutrient to beneficial bacteria
Should escape digestion in the stomach and reach Intestine
Should promote the proliferation of beneficial bacteria (Lactiobaccillus , Bifidobacteria)
PREBIOTICS & PROBIOTICS : IS THERE ANY DIFFERENCE ?
Probiotics Nature of the Prep Microorganism Prime Fn To kill harmful pathogen Prebiotics Food supplement (eg: FOS) or Microorganism (eg : S.F ) To supply nutrition (Killing the pathogen is an additional effect)
PREBIOTICS – WHICH IS BETTER ?
FOS OR LIVE MUTATED BACTERIA ?
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
PRE/PROBIOTICS - INDICATIONS
1. Infective diarrhea (viral, bacterial) 2. Antibiotic associated diarrhea 3. Lactose intolerance 4. Recurrent aphthous ulcers and stomatitis 5. Travelers’ diarrhea 6. Inflammatory IBD (Ulcerative colitis, Crohn’s) 7. Irritable bowel syndrome 8. Post operative state 9. Pouchitis 10. Diverticular disease of colon
INFECTIOUS DIARRHEA
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
PROBIOTICS IN PREVENTION AND TREATMENT OF DIARRHEA
PURPORTED MECHANISMS OF ACTION
Free amino acids Organic acids Neutralization of dietary carcinogens β-Galactosidase activity Probiotics Immunostimulatory Oligosaccharides Cholesterol assimilation Short chain fatty acids Bioactive peptides Bacteriocin Antioxidant Survival and adhesion competitions with pathogenic bacteria
Non-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 Immune Response
L L APC Adhesive M L L Th 0
Cell mediated response
IL-2 ↑ IFN- γ ↑
+
TGF-β↓ IL-4 ↓ IL-10 ↓
Antibody mediated response
Microorganisms Intestinal Epithelium B IgG ↑ IgM ↑ IgE ↓ B Th 2
IL-2 ↑ IFN-γ ↑ TNF-α ↑ IFN-α ↑ Natural killer cells ↑ Macrophages ↑ Cytotoxic T-lymphocytes ↑
Th 1 Viruses Tumors IgA
POTENTIAL MECHANISMS OF PROBIOTICS FOR PREVENTION OR TREATMENT OF DIARRHEA 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
ANTIBIOTIC ASSOCIATED DIARRHEA
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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PROBIOTICS DECREASE ADD
Volcano lesions in AAD Pseudomembranous Colitis
•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
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• 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.
HIGHEST RISK OF AAD…
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.
Diarrhea is a common adverse effect of antibiotic treatments . Antibiotic associated diarrhea occurs in about 5-30% of patients
BMJ 2002;324:1345-1346 (8 JUNE)
PROBIOTICS DECREASE DIARRHEA
International Microbiology 2004 ; Mar 7(1) 59-62
CLOSTRIDIUM DIFFICILE ASSOCIATED DIARRHEA (CDAD)
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CLOSTRIDIUM DIFFICILE ASSOCIATED DIARRHEA (CDAD)
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LACTOSE INTOLERANCE
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.
RECURRENT APHTHOUS ULCERS / STOMATITIS 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.
TRAVELER’S DIARRHEA
Transmission of infection:
Feco-oral route / fingers and flies.
Affects tourists traveling ; Shigella
Travelers’ diarrhea can be prevented by regular prophylactic intake of beneficial bacteria
One week before travel, during travel, one week after completion of travel.
IBS – IRRITABLE BOWEL SYNDROME
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
IBD – INFLAMMATORY BOWEL DISEASE
Inflammation in GI Tract
Crohn’s Disease Ulcerative Colitis Small & Large intestine Large intestine (Rectum & Colon) Crohn’s disease Ulcerative colitis
IBD – INFLAMMATORY BOWEL 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
POUCHITIS
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
DIVERTICULITIS
Diverticula - Formation of small bulges / bags in the colon
Diverticulitis – Inflammation/ Infection in the diverticula
SYMBIOTIC
Mixture of Pre and Probiotic
Probiotics – Helps in reducing the PPMs
Prebiotics – Helps in Providing food for Probiotics
BIFILAC
Lactobacillus
sporogenes
Streptococcus
faecalis
T-110 Clostridium
butyricum
TO-A Bacillus
mesentericus
TO-A 50 million ( Probiotic) 30 million ( Prebiotic) 2 million ( Prebiotic) 1 million ( Prebiotic)
PREBIOTICS IN BIFILAC
Streptococcus faecalis T-110 Clostridium butyricum TO-A Bacillus mesentericus TO-A 30 million ( Prebiotic) 2 million ( Prebiotic) 1 million ( Prebiotic)
PREBIOTICS – HOW DO THEY GET FOOD ?
Clostridium Butyricim ( Small & Large) Streptococcus faecalis ( Small ) Bacillus Mesentricus ( Small) 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.