Living microorganisms in therapy


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Living microorganisms in therapy

  1. 1. Living Microorganisms in Therapy -Dr CSN Vittal
  2. 2. Gut Flora
  3. 3. At birth .. Gut is sterile
  4. 4. Intestinal colonization .. – Begins with the process of birth. – Normal vaginal delivery permits transfer of bacteria from mother to infant. – Breast Fed: >90% of intestinal bacteria are bifidobacteria. – Top Fed: Enterobacteria and gram –ve bacteria predominate.
  5. 5. good bad
  6. 6. Probiotics Mode of Action • Producing antimicrobial substances, bacteriocins, peptides & Small Chain Fatty Acids • Producing volatile acids and lactic acid which reduce the intestinal pH, • Stimulating mucus secretion, • Strengthening gut barrier function, • Competing for adhesion sites, • Competing for nutrients, • Stimulating specific and non-specific immune responses, etc. • Reduction of bacterial translocation
  7. 7. L APC 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 M Intestinal Epithelium Microorganisms B IgG ↑ 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
  8. 8. Eubiosis Bifidobacteria Lactobacillus Assosiated with health Clostridia Detrimental to health
  9. 9. Dysbiosis •Diarrhoea •Radiation •Steroids •Chemotherapy •Inflammation •Chronic illness •Postoperative stage •Antibiotics
  10. 10. Restoration of Gut Flora Biotherapy : The use of biological agents constitutes a purposeful attempt to modify the relationship with our immediate microbial environment, in ways that may benefit human health. Using living microorganisms
  11. 11. • Fermentation – as ancient as 2500 BC – noticed in Sumerian wall painting and Old Testament (Genesis 18:8) • Eli Metchinkoff credited long life of certain races to consumption of large amounts of fermented milk products. (1908) • Lily & Stillwell coined the term ‘probiotics’. (1965) • Professor Gibson & Dr Marcel Roberfroid coined the term "prebiotics" . (1995) Historical Aspects
  12. 12. Probiotics (Gk: for life) “Live microbial feed supplement which beneficially affects the host animal by improving its intestinal microbial balance” - Fuller (1989)
  13. 13. Ideal Probiotic • Contain viable microorgnisms which naturally colonized in human gut. • Should be safe with no pathogenic effects. • Able to survive in gastric transit and can remain surviving in the intestine. • Have beneficial effect and improve health of the individual ingesting them. Gibson RG, Probiotics and prebiotics; gut microflora management for improved health, Medicine Digest 2003;3:56-59
  14. 14. List of some Probiotics 1 Lactobacillus reuteri Lactobacillus GG L casei L bulgaricus L plantarum L rhamnosus L salivarius L acidophilus L gasseri L delbrueckii L johnsonii 0 3 Streptococcus thermophilus S. faecalis Saccharomyces boulardii S. cerevisiae Enterococcus faecium Leuconostoc mesenteroides Propionibacterium freudenreichii 2 Bifidobacterium bifidus B longuim B infantis B breve B bifidum B adolescentis • (Gorbach, Goldin)
  15. 15. Food Sources Yogurt – L.acidophilus – L.bulgaricus – L.thermophilus Bitter Milk – L.lactus – S.cremoris Sour Cream – S.cremoris Yoghurt / Dahi consumption is folklore, many may not know that 1 tsp of contains 6 billion organisms sauerkraut cheese Miso soup kimchi
  16. 16. Prebiotics "Unlike probiotic bacteria, prebiotic carbohydrates are not destroyed when cooked." Nondigestible food ingredients that may beneficially affect the host by selectively stimulating the growth and/or the activity of a limited number of bacterial species already established in the colon, and thus in effect improve hosthealth’ (Gibson and Roberfroid, 1995)
  18. 18. Prebiotics Mechanism of Action • Escape digestion in the upper gastrointestinal tract and be used by the microorganisms comprising the colonic microflora. • They mainly stimulate the growth of bifidobacteria, for which reason they are referred to as bifidogenic factors. • Primarily affect the large intestine. • Increases short-chain fatty acid production in the colon, and subsequent increased mucin production in the GI tract
  19. 19. A mixture of pro and prebiotics with an ability to improve survival and regeneration of GI flora which in turn will enhance the host health Synbiotics Certain probiotic- produced, soluble factors, which were sufficient to elicit the desired response Postbiotics
  20. 20. Colonic Cancer Urogenital infections IBD / IBS Atopic Disorders H Pylori infection Lactose intolerance Prevention / Tt Of Diarrheas NEC ConstipationGingivitis / Caries Hypertension Cholesterol i Ischemic Heart Syndromes Infantile ColicRegurgitation NAFLD Hepatic Encephalopathy
  21. 21. EVIDENCE BASED MEDICINE • “The process of systematically finding, approving and using contemporaneous research finding as the basis for clinical decisions.” Archie Cochrane
  22. 22. LEVELS OF EVIDENCE Level 1 A Evidence from high quality randomized controlled trials with statistically significant results and few limitations in their design OR conclusions from systematic reviews of the trials. Level 1 B Single high quality clinical trials that have clearly shown positive or negative results with narrow intervals of confidence, so that it is unlikely that the trend would change in future studies Level 2 Controlled trials without randomization. Cohort studies or case control studies preferably from more than one center or group Multiple time series with or without intervention Opinions of authorities based on clinical experience and case reports Level 3
  23. 23. Grade A recommendation (level 1A evidence) • Treatment of acute infectious diarrhoea in children. • Prevention of antibiotic associated diarrhoea. • Prevention of nosocomial diarrhoea in children. • Treatment of lactose malabsorption. Pro / Prebiotics in Therapeutics
  24. 24. Grade A recommendation (level 1B evidence) • Prevention of pouchitis and maintenance of remission. • Prevention of postoperative infections. • Prevention and management of paediatric atopic diseases. Pro / Prebiotics in Therapeutics
  25. 25. • Prevention of travellers’ diarrhoea. • Prevention of sepsis associated with severe acute pancreatitis. • Maintenance of remission of ulcerative colitis. • Lowering of blood cholesterol. Grade B recommendation (level 2 evidence) Pro / Prebiotics in Therapeutics
  26. 26. ?? Living Microorganisms in Prophylaxis
  27. 27. Supplementation of Infant Formula With Probiotics / Prebiotics • PROBIOTICS: – For healthy infants, the available scientific data suggest that the administration of currently evaluated probiotic - supplemented formula to healthy infants does not raise safety concerns with regard to growth and adverse effects. – The administration of probiotic-supplemented infant formula during early life (4 months of age) does not result in any consistent clinical effects. – In general, there is a lack of data on the long-term effects of the administration of formula supplemented with probiotics – Considering the above, the Committee does not recommend the routine use of probiotic- supplemented formula in infants. • A Systematic Review and Comment by the ESPGHAN Committee on Nutrition (JPGN 2011;52: 238–250)
  28. 28. Supplementation of Infant Formula With Probiotics / Prebiotics • PREBIOTICS: – the administration of formula supplemented with some prebiotics is associated with some clinical effects, such as increased stool frequency and stool softening, the clinical relevance of which remains questionable. – Only 1 RCT with methodological limitations demonstrating that the administration of extensively hydrolysed formula supplemented with GOS/FOS is associated with a reduced risk of some allergic reactions and some types of infections. – There is a lack of data on the long-term effects of the administration of formula supplemented with prebiotics. – Considering the above, the Committee does not recommend the routine use of formula supplemented with prebiotics in infants. • A Systematic Review and Comment by the ESPGHAN Committee on Nutrition (JPGN 2011;52: 238–250)
  29. 29. How Safe are these ‘Living Drugs’ ! • Infection - Sepsis • Deleterious metabolic activities • Immune déviation or excessive immune stimulation • Microbial resistance
  30. 30. Proposed risk factors for probiotic sepsis Major risk factors 1) Immune compromise, including a debilitated state or malignancy 2) Premature infants Minor risk factors 1) Central Venous Catheter 2) Impaired intestinal epithelial barrier 3) Administration of probiotic by jejunostomy 4) Concomitant administration of broad spectrum antibiotics which probiotic is resistant 5) Probiotics with properties of high mucosal adhesion or known pathogenicity 6) Cardiac valvular disease (Lactobacillus probiotics only) The presence of a single major or more than one minor risk factor merits caution in using probiotics. Am J Clin Nutr June 2006 vol. 83 no. 6 1256-1264
  31. 31.  Paucity of information regarding the mechanisms through which probiotics act, probiotic interactions, strain-specific utility  Lack of appropriate administrative regimens,  Dosage uncertainty,  Possible adverse effects in prematurely or with immune deficiency AREAS OF UNCERTAINTY IN THE USE OF PROBIOTICS Probiotic use in clinical practice: what are the risks? Boyle RJ, Robins-Browne RM, Tang ML. Am J Clin Nutr. 2006 Jun;83(6):1256-64;quiz1446-7
  32. 32. Conclusion Avoiding an excessive optimism and the thought that an efficacious panacea for all troubles has been found, there are sound reasons to believe that probiotics & prebiotics, can influence human health, through the prevention and therapy of many diseases, although Further studies are needed to explore mechanistic issues and probiotic interactions. In view of the increasing use of probiotics as health supplements and therapeutic agents, clinicians need to be aware of the risks and benefits of these treatments.
  33. 33. • C.S.N. Vittal Than Q
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