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 2 LOUIS PASTEUR (1822 - 1895) Potential benefits of Lactobacillus~125 yrs ago METCHNIKOFF ELIE (1848-1916) 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 4 COLONIZATION OF GUT 1st Year;: > 200 bacterial species Adult : 500-600 bacterial species Elderly: 300 Bact. Species Chr. Intestinal disorders 5 RELATIVE PROPORTION For context – Total Cells Theirs ~ 100,000 billion. Ours ~ 10,000 billion. GUT FLORA IN BREAST FED VS FORMULA FED BABIES 7 Friendly bacteria Unfriendly / harmful Bacteria – Probiotics – Pathogens COMMON FLORA Facultative Anaerobes Staph. Aureus, albus Strict anaerobes 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 LACTOBACILLUS: BIFIDOBACTERIA: SACCHAROMYECES: 9 PROBIOTICS ( “FOR LIFE’’) Probiotics (Friendly Bacteria) Normalise Intestine Suppression of PPMs Immunomodulation Strengthens immunity Metabolic effects Production of vitamins; improves digestion Intestinal mucosal integrity Alleviate food allergy symptoms Lactose tolerance Regulation of bowel movement IBS Conrol of IBD 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 Prebiotics Nature of Microorganism the Prep 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) 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 Neutralization of Organic acids dietary carcinogens β-Galactosidase activity Oligosaccharides Probiotics Immunostimulatory Cholesterol assimilation Antioxidant Short chain fatty acids Survival and adhesion Bioactive peptides Bacteriocin competitions with pathogenic bacteria Adhesive Non-adhesive Microorganisms M = M cells of intestinal epithelium L = Lymphocytes Immune Response APC = Antigen presenting cells Intestinal Epithelium Th = T-helper cells M IL = Interleukines TGF = Tumour growth factor L IFN = Interferon TNF = Tumour necrosis factor L L APC Ig = Immunoglobulin L Th0 IgG ↑ Cell mediated response IL-2 ↑ IFN- γ ↑ + TGF-β↓ IL-4 ↓ IL-10 ↓ B Antibody mediated response IgM ↑ IgE ↓ B Th2 Th1 IgA IL-2 ↑ IFN-γ ↑ TNF-α ↑ IFN-α ↑ Natural killer cells ↑ Macrophages ↑ Cytotoxic T-lymphocytes ↑ Viruses Tumors 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 24 PROBIOTICS DECREASE ADD Pseudomembranous Colitis Volcano 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 31 • 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) 35 CLOSTRIDIUM DIFFICILE ASSOCIATED DIARRHEA (CDAD) 36 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 50 million ( Probiotic) Streptococcus faecalis T-110 30 million ( Prebiotic) Clostridium butyricum TO-A 2 million ( Prebiotic) Bacillus mesentericus TO-A 1 million ( Prebiotic) PREBIOTICS IN BIFILAC Streptococcus faecalis T-110 30 million ( Prebiotic) Clostridium butyricum TO-A 2 million ( Prebiotic) Bacillus mesentericus TO-A 1 million ( Prebiotic) PREBIOTICS – HOW DO THEY GET FOOD ? On ingestion, 3 mutated Streptococcus faecalis ( Small ) live bacteria continue to proliferate in the GI tract by a process of Symbiosis Symbiosis : Biological association of two or Clostridium Butyricim ( Small & Large) Bacillus Mesentricus ( Small) more species to their mutual benefit. THANK YOU ALL