Prebiotics and Probiotics

1. 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) Prebiotics and Probiotics visit: www.drsarma.in www.youtube.com/user/drsarmaji

2. Antibotics Probiotics Prebiotics Synbiotics

3. Louis Pasteur (1822 - 1895) Metchnikoff Elie (1848-1916) Potential benefits of Lactobacillus~125 yrs ago 1905: Concept of Probiotics

4. 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

5. Colonization of gut • 1st Year;: > 200 bacterial species • Adult : 500-600 bacterial species • Elderly: 300 Bact. Species • Chr. Intestinal disorders

6. For context – Total Cells • Theirs ~ 100,000 billion. • Ours ~ 10,000 billion. Relative Proportion

7. Gut Flora in Breast Fed vs Formula Fed Babies

8. Friendly bacteria – Probiotics Unfriendly / harmful Bacteria – Pathogens

9. Common flora Facultative Anaerobes Strict anaerobes 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 LACTOBACILLUS: BIFIDOBACTERIA: SACCHAROMYECES:

10. Probiotics ( “For Life’’)

11. Probiotics (Friendly Bacteria) Normalise Intestine Immunomodulation Metabolic effects Suppression of PPMs Strengthens immunity 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)

12. Inhibit Potentially Pathogenic Microorganisms (PPMs) • Reduction in Intestinal pH ( through production of SCFAs) • Production of bacteriocins • Competitive blocking of adhesion sites • Competition for nutrients Mechanism of Action

13. MOA of Probiotics

14. Types of Probiotics • Most abundant Probiotic in GI • Lactobacillus: • Acidophilus, • Rhamnosus, GG • Plantarum, • Reuteri, • Bulgaricus, • Sporogens • Casei • Action only in Small intestine

15. Types of Probiotics • Bifidobacteria • 32 different species : Longum, Bifidum, infantis etc • Most abundant probiotic next to lactobacilli Sp. in the GIT • Action : Large Intestine

16. Apart from the general Probiotics effect , Bifidobacteria helps is Glutamine synthesis Glutamine helps in maintaining the mucosal integrity NH3 + Glutamic acid ------------> Glutamine Uniqueness of Bifidobacteria Bifidobacteria

17. Types of ProbioticsSaccharomyces boulardii • Saccharomyeces: • Boullardii, • Salivarium, • Thermophilus • Non colonising yeast – so needs repeated readministration • Action in large intestine

18. 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 • 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

19. 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 Is Probiotic Prepn withBifidobacteria Useful ?

20. Prebiotics • Non-digestible dietary supplements, which provide ‘’nutrition’’ for Probiotics • Oligosaccharides (fructo-oligosaccharides or FOS), Inulin, Lactulose, Lactitol • Mutated Bacterial Species (Streptococcusfaecalis, Clostridiumbutyricum, Bacillus mesentericus) • Advantage of Prebiotics in bacterial form : Addl. Probiotic activity ( Intrinsic Probiotic activity)

21. 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)

22. Prebiotics & Probiotics : Is there any difference ?

23. 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 Prebiotics – Which is better ?FOS or live mutated bacteria ?

24. 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

25. 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 Infectious diarrhea

26. Probiotics in prevention and treatment of diarrhea

27. Purported mechanisms of action Free amino acids Organic acids Neutralization of dietary carcinogens β-Galactosidase activity Probiotics Oligosaccharides Immunostimulatory Cholesterol assimilation Antioxidant Short chain fatty acids Survival and adhesion competitions with pathogenic bacteria Bioactive peptides Bacteriocin

28. Adhesive Non-adhesive Microorganisms 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 Intestinal Epithelium M L L L APC L Th0 IgG ↑ IgM ↑ IgE ↓ B Antibody mediated response Cell mediated response TGF-β↓ IL-4 ↓ IL-10 ↓ IL-2 ↑ IFN- γ ↑ + B Th2 Th1 IgA IL-2 ↑ IFN-γ ↑ TNF-α ↑ IFN-α ↑ Viruses Tumors Natural killer cells ↑ Macrophages ↑ Cytotoxic T-lymphocytes ↑

29. 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 Potential mechanisms of probiotics forprevention or treatment of diarrhea

30. 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

31. 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

32. 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

33. 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)

34. Probiotics decrease Diarrhea International Microbiology 2004 ; Mar 7(1) 59-62

35. Clostridium difficile Associated Diarrhea (CDAD)

36. Clostridium difficile Associated Diarrhea (CDAD)

37. 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.

38. 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.

39. 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.

40. 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 IBS – Irritable bowel syndrome

41. Crohn’s disease Ulcerative colitis • Inflammation in GI Tract IBD – Inflammatory Bowel Disease Crohn’s Disease Small & Large intestine • Ulcerative Colitis • Large intestine (Rectum & Colon)

42. 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 IBD – Inflammatory Bowel Disease

43. 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

44. Diverticulitis • Diverticula - Formation of small bulges / bags in the colon • Diverticulitis – Inflammation/ Infection in the diverticula

45. Mixture of Pre and Probiotic Probiotics – Helps in reducing the PPMs Prebiotics – Helps in Providing food for Probiotics Symbiotic

46. 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) Bifilac

47. Streptococcus faecalis T-110 30 million ( Prebiotic) Clostridium butyricum TO-A 2 million ( Prebiotic) Bacillus mesentericus TO-A 1 million ( Prebiotic) Prebiotics in Bifilac

48. Prebiotics – How do they get food ? 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.

49. Thank you all