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GUT Microbiota in health and disease

GUT Microbiota in health and disease. Moderator – Dr Sunil K Mathai Panelists – Dr Benoy Sebastian, Dr Geetha M, Dr Antony Chettupuzha , Dr Joseph John. GUT : How sterile is it? – AC. Sterile at birth…. Gut Microbiota.

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GUT Microbiota in health and disease

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  1. GUT Microbiota in health and disease Moderator – Dr Sunil K Mathai Panelists – Dr Benoy Sebastian, Dr Geetha M, Dr Antony Chettupuzha, Dr Joseph John

  2. GUT : How sterile is it? – AC

  3. Sterile at birth…

  4. Gut Microbiota Number of intestinal microbial cells is 10 times greater than the number of human body cells Approximately 150 times larger than the human gene complement, with an estimated set of 3.3 million microbial gene Bacteroides Firmicutes Verrucomicrobia Fusobacteria Proteobacteria Actinobacteria Cyanobacteria

  5. Infant feeding: Role in development of GUT microbiota- GM

  6. Infant feeding – Role in devpt of microbiota • Best microbiota in babies born by vaginal delivery , roomed-in with mother & breast-fed • Worst in ceasarian delivery, admitted in ICU, formula-fed and administered IV antibiotics

  7. GUT Microbiota a Vital organ – BS

  8. Microbial ecosystem • Upto 100 trillion bacteria - 500 different species • Outnumber human somatic and germ cells by 10 fold • Marked microbial diversity among different individuals • Each person has his own distinctive pattern of microbial composition • Determined by genetic and environmental factors

  9. Hidden Metabolic Organ

  10. Protective Function • Pathogen Displacement • Antimicrobial factors • Immune system development • Promotes anti inflammatory cytokines and down regulates pro inflammatory cytokines • Induces regulatory T cells

  11. Structural Functions • Barrier Fortification • Induction of IgA • Apical tightening of tight junction • Enhanced mucinprodution

  12. Metabolic Functions • Short chain fatty acids • Metabolizes dietary carcinogens • Synthesis of vitamins • Ion absorption

  13. GUT Microbiota in Growth and Development – GM

  14. GUT microbiota in growth and development • Gut and microbiotia – symbiotic relationship • Modulates gut immune system via “ cross-talk”

  15. In the newborn period commensal bacteria provide the immune system with stimuli which causes maturation • If you get the right bacteria – prevents a number of AI conditions, atopy, allergy etc

  16. GUT dysbiosys – Good, Bad and Ugly – JJ

  17. Good

  18. Dysbiosis is a state in which the microbiota becomes altered due to an alteration in the composition of the microbiota, a change in bacterial metabolic activity and/or a shift in local distribution of communities. • Role in several diseases. • Factors altering the gastrointestinal ecosystem include • antibiotics, • psychological and physical stresses, • radiation, • altered peristalsis and • dietary changes

  19. Bad

  20. Ugly

  21. Probiotic, Prebiotic and Synbiotic – The concept – AC

  22. Probiotic means for life… WHO definition(2001): “Live micro-organisms which, when administered in adequate amounts, confer a health benefit on the host” Lilly, D. M. and R. H. Stillwell. 1965. Probiotics:  growth promoting factors produced by microorganisms. Science 147:747-748 Sour milk with lactobacilli prolongs life 1907 Parker, R. B. 1974. Probiotics, the other half of the antibiotic story. Anim. Nutr. Health. 29:4-8 Fuller, R. 1989. Probiotics in man and animals. J. Appl. Bacteriol. 66:365-378 IlyaIlyichMechnikov

  23. Prebiotic Definition: “A dietary prebiotic is a selectively fermented ingredient that results in specific changes, in the composition and/or activity of the gastrointestinal microbiota, thus conferring benefit(s) upon host health.” They are dietary fibers with a well-established positive impact on the intestinal microflora Non-digestible Oligosaccharides Inulin Oligofructose (trans)galactooligosaccharides Term coined by Glen Gibson 1995

  24. Synbiotics

  25. Selection of a Probiotic candidate – Which organism and why – BS

  26. A probiotic strain is identified by the genus, species, and an alphanumeric designation

  27. An ideal probiotic • Able to survive the passage through the digestive system • Able to attach to the intestinal epithelia and colonise. • Able to maintain good viability • Able to utilise the nutrients and substrates in a normal diet • Non pathogenic and non toxic • Capable of exerting a benificial effect on the host • Stability of desired characteristics during processing, storage and transportation

  28. Clinically Useful strains • Lactobacillus sp. • reuteri • casei • ramnosus • Acidophilus • Streptococcus sp. • Bifidobacterium sp. • Infantis (breastmilk) • lactis • longum • breve • bifidum • Sacharomycesboulardii • Enterococcus sp • Mixtures

  29. Before marketing • Purified strain of microbe • In vivo safety and efficacy studies in animals • In vivo safety,efficacy and effectiveness studies in human beings

  30. Labeling Requirements • Genus,species and strains • Minimum valuable number of each probiotic strain at which efficacy is claimed • Shelf life • Evidence based health claims • Serving size • Storage conditions

  31. Mechanism of action of ProbioticsJJ

  32. Antimicrobial actions: • Inhibit growth of pathogenic enteric bacteria by: • Decreasing luminal pH • Secreting bactericidal proteins • Resisting colonisation • Competing for nutrients with pathogens • Modifying pathogen-derived toxins • Stimulating defensin production • Blocking epithelial binding • Stimulating mucus production

  33. Barrier function: • Improve epithelial and mucosal barrier function by: • Producing SCFAs • Increase barrier integrity • Enhance mucus production • Immune function: • Alter host immune response by: • Modulating cytokine profiles - induce IL-10 and TGF- secretion and decrease TNF and IFN- expression • Activating local macrophages and increase secretoryIgA production both locally and systemically • Activating Treg cells • Inducing hyporesponsiveness to food antigens • Dampening inflammatory responses

  34. Daily Kerala diet; Is it probiotic rich? GM

  35. Daily Kerala Diet – is it probiotic rich? • Traditional fare – • Fermented rice • Healthy and “prebiotic rich” • Newer diets • Neither healthy nor probiotic rich • Added probiotics may benefit

  36. Available probiotic preparations; are all the same? AC

  37. Probiotic Platter ENTEROGERMINAbacillus clausii VSL#3 Streptococcus thermophilus , bifidobacteriumbreve , bifidobacteriumlongum , bifidobacteriuminfantis , lactobacillus acidophilus , lactobacillus plantarum , lactobacillus paracasei , lactobacillus delbrueckiisppbulgaricus. DAROLAC lactobacillus acidophilus lactobacillus rhamnosusbifidobacteriumlongumSaccharomycesboulardii. BIFILAC Streptococcuslactobacillus clostridium butyricum bacillus mesentericus VELGUT lactobacillus acidophilus , lactobacillus plantarum , lactobacillus casei , lactobacillus rhamnosus , bifidobacteriumbreve , bifidobacteriumlongum , bifidobacteriuminfantis , Streptococcus thermophilus , Saccharomycesboulardiifructooligosaccharides YOGUT oligofructose , lactobacillus acidophilus , lactobacillus rhamnosus , bifidobacteriumbifidum , bifidobacteriuminfantis , bifidobacteriumlongum. ECONORM Saccharomycesboulardii BECELAC-PB Streptococcus faecalis clostridium butyricum bacillus mesentericus lactobacillus sporogenes PREPRO Streptococcus faecalis clostridium butyricum bacillus mesentericus lactobacillus acidophilus PRO-GURT : , fructo oligosaccharide 100 mg, lactobacillus acidophilus 700 million cells, lactobacillus rhamnosus 400 million cells, lactobacillus paracasei 300 million cells, lactobacillus plantarum 300 million cells, lactobacillus bulgaricus 300 million cells, bifidobacteriumlongum 300 million cells, bifidobacteriuminfantis 300 million cells, bifidobacteriumbreve 300 million cells, Streptococcus thermophilus 400 million cells, Saccharomycesboulardi

  38. Are all the same?

  39. Indications of Probiotics in Adults BS

  40. Irritable Bowel syndrome • Metaanalysis - Moyyedi et al Gut 2010 • 19 RCTs – 1650 patients • Significant reduction in symptoms with an NNT of 4 • Trend towards improving pain and bloating • No effect on constipation • Bifidobacteriuminfantis35624 – superior

  41. Diarrhoea

  42. Inflammatory Bowel Disease • Yet to meet the high expectations predicted by the theoretical data • No significant or consistent benefit in Crohn’s disease • In UC a modest effect in inducing and maintaining remession in mild to moderate UC • Escherichia coli Nissle and VSL # 3

  43. Pouchitis • Significant reduction first episode of pouchitis • Maintenance of remission of recurrent or refractory pouchitis • Used VSL # 3 GosselinketalDis Colon Rectum 2004 Mimura et al Gut 2004

  44. Other GI Diseases

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