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Ramakrishnan
- 1. Probiotics and intestinalhealth B.S. Ramakrishna Director SIMS Institute of Gastroenterology, Hepatobiliary Science & Transplantation Vadapalani, Chennai
- 2. Gut bacteria-human interaction •Symbiosis • Commensalism • Pathogenicity
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- 4. Fecal bacterial communitiesin Indians Bacteroidetes Firmicutes Sandya Rani et al Lactobacillus <2% Bifidobacteria 3%
- 5. Intestinal bacteria • Bacteroidesgroup 18% • Clostridium coccoides group 16% • Clostridium leptum group 14% • Atopobium group 7% • Bifidobacterium 3% • Lactobacillus 0.2%
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- 8. Metabolic functions • Fermentunabsorbed carbohydrate • Detoxify harmful substances
- 9. Ramakrishna BS J GastroenterolHepatol 2013
- 10. Fermentable carbohydrate Acetate PropionateButyrate Mostly used up in colonic epithelium Energy production Lipid synthesis Mucosal proliferation Mucosal blood flow Epithelial cell differentiation Portal circulation Metabolized in liver Reduces: Serum cholesterol Fasting glucose Mostly bypasses liver Metabolised in peripheral tissues Bacteria
- 11. SCFA maintain colonichealth • Improve epithelial cell energy use in colitis Ahmed et al, Gut 2000 • Increase sodium and water absorption Ramakrishna et al, NEJM 2000 • Strengthen the mucosal barrier Venkatraman et al, Scand J GE 2000 • Hasten epithelial cell renewal after injury Venkatraman et al, Scand J GE 1999 • Reduce inflammation in colitis by inhibiting HSP 70 & NF-κB Venkatraman et al, Am J Physiol 2003
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- 13. Genetic obesity inmice (Ob/ob) • Reduction in Bacteroidetes; increase in Firmicutes, Archaea • Enrichment for hydrolases (break down of indigestible CHO) • Enrichment for transport proteins that can import the breakdown products • Enrichment for enzymes involved in fermentation to SCFA Turnbaugh et al, Nature 2006
- 14. Diet-induced obesity inmice • Reduction in Bacteroidetes; increase in Firmicutes • Increased phosphotransferase systems, import and fermentation of simple sugars • Enrichment for fructosidases • Decrease in genes for motility proteins, bacterial chemotaxis Turnbaugh et al, Cell Host Microbe 2008
- 15. Balamurugan et al,Br J Nutr 2009 Microbiota & obesity in children Faecalibacterium prausnitzii
- 16. Fecal microbiota alterationsin obesity vary in different populations • Increased Faecalibacterium prausnitzii in obese children Balamurugan et al, Br J Nutr 2009 • Increased Lactobacillus and reduced Bacteroidetes in obese individuals Armougom et al, PLoS One 2009 • Increased Enterobacteriaceae in obese pre-school children Karlsson et al, Obesity 2012 • Increased Bacteroidetes in obese individuals at phylum level; increased Archaea in obese (5 adults) Patil et al, J Biosci 2012
- 17. Energy salvage andmicrobiota change • 20% increase in Firmicutes and 20% decrease in Bacteroidetes is associated with 150 kCal increase in energy harvest Jumpertz et al, AJCN 2011
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- 19. No evidence toshow that probiotics are effective in management of obesity
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- 21. Microbiota and ironabsorption • Iron normally absorbed from duodenum • Transporters for iron absorption are also expressed in caecum & ascending colon • Iron absorption from proximal colon in experimental animals is enhanced by fermentable carbohydrate Levrat et al, J Nutr 1991 Scholz-Ahrens & Schrezenmeier, Br J Nutr 2002 Scholz-Ahrens & Schrezenmeier, J Nutr 2007
- 22. Balamurugan et al,Br J Nutr 2010 Microbiota & iron deficiency
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- 25. Microbiota in coloncancer Balamurugan R et al, J Gastroenterol Hepatol 2008
- 26. Experimental evidence foruse of probiotics in colon cancer • L. acidophilus and Bifidobacterium bifidum reduced proliferative zone and fecal pH in patients at high risk for colon cancer • Consumption of lactobacilli by human volunteers reduced mutagenicity of urine and feces associated with ingestion of carcinogens in cooked meat • Lactobacillus casei Shirota – anti-tumor and anti-metastatic effect on transplantable tumor cells – Induced IFN-γ, TNFα, IL1β which increased survival of tumor- bearing mice • Lactobacillus peptidoglycan dose-dependently reduced growth of CT-26 cancer cells in BALB/c mice via increased apoptosis
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- 28. Protect against harmfulbacteria • Displace pathogens • Compete for nutrients • Compete for receptors • Produce antimicrobial substances including secretory IgA
- 29. PROBIOTICS, ENTERIC &DIARRHEAL DISEASES & GLOBAL HEALTH GA Preidis, C Hill, RL Guerrant, BS Ramakrishna, GW Tannock, J Versalovic Gastroenterology 2011
- 30. PROBIOTICS, ENTERIC &DIARRHEAL DISEASES & GLOBAL HEALTH GA Preidis, C Hill, RL Guerrant, BS Ramakrishna, GW Tannock, J Versalovic Gastroenterology 2011
- 31. B aseline Probiotic yoghurt N orm alyoghurt 0 1000 2000 3000 4000 P=0.0184 P=0.0822 SecretoryIgAmg/gstool Probiotic yoghurt increasedfecal secretory IgA in southern Indian healthy volunteers. Jayakanthan et al, Nutr J 2011
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- 33. Lactobacillus acidophilus group ControlDSS Probiotic 0.000000 0.000002 0.000004 0.000006 0.000008 0.000010 0.000012 * @ Relativedifference Bifidobacterium species Control DSS Probiotic 0.0000 0.0005 0.0010 0.0015 0.0020 0.0025 * **,@ Relativedifference CONTROL DSS PROBIOTIC 0 250 500 750 1000 1250 * ** TNF-αpg/ml
- 34. Probiotics and experimentalcolitis • In IL-10 knockout mice, colitis is attenuated by – Lactobacillus reuteri – VSL#3 – Lactobacillus plantarum – Lactobacillus salivarius • In HLA B27 transgenic rats – Lactobacillus plantarum prevents colitis
- 35. CLINICAL EVIDENCE BASE FORPROBIOTIC USE IN IBD
- 36. Ulcerative colitis –inducing remission • Induction of remission – No effect when added to conventional therapy Mallon et al, Cochrane Database Systematic Reviews 2007 – VSL3 superior to placebo in inducing remission in mild to moderate UC Sood et al, Clin Gastroenterol Hepatol 2009
- 37. Uc – maintainingremission Investigator Probiotic Outcome measure Comparison group Result Kruis 1997 E. coli Nissle 1917 Maintenance of remission Mesalamine Equivalent Rembacken 1999 E. coli Nissle 1917 Maintenance of remission Mesalamine Equivalent Kruis 2001 E. coli Nissle 1917 Maintenance of remission Mesalamine Equivalent Ishikawa 2003 Bifidobacteria- fermented milk Maintenance of remission Placebo Superior
- 38. Pouchitis Investigator Probiotic Outcome measure Comparison group Result Gionchetti 2000 VSL#3Maintenance of remission Placebo Superior Mimura 2002 VSL#3 Maintenance of remission Placebo Superior Gionchetti 2003 VSL#3 Prevention after ileostomy closure Placebo Superior
- 39. Crohn’s disease • Treatmentof active disease – No effect • Maintenance of remission after medical or surgical therapy – 7 small studies with significant heterogeneity – Probiotics not effective – Small sample sizes. Rolfe et al, Cochrane Database Systematic Reviews 2006
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- 41. Probiotics condition theimmune system Shanahan F ett al, EMBO J 2006
- 42. Balance of bacteriain the gut Protective/Probiotic Lactobacillus species Bifidobacterium species Selected E. coli Saccharomyces boulardii Clostridium butyricum Aggressive Selected Bacteroides Enterococcus faecalis Pathogenic E. coli Fusobacterium varium Intestinal Helicobacter
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- 45. Probiotics and oraltolerance • Oral tolerance is deficient in germ-free mice – Due to failure to generate suppressor cells – Restored by Bifidobacterium infantis Sudo et al J Immunol 1997 – Restored by E. coli LPS Wahnemuehler et al, J Immunol 1982 • Oral Lactobacillus produced an increase in CD4+ T cells secreting IL-10 and TGF-β
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- 47. Old age ….and natural death is due to auto-intoxication produced by putrefactive microbes in the colon. … to increase one's life expectancy, it is necessary to replace the putrefactive microbes with a healthy flora of lactic acid bacteria. The Nature of Man Elie Metchnikoff, 1908
- 48. World Gastroenterology OrganisationGlobal Guidelines Probiotics and prebiotics November 2016 Review Team First Name Country Accept RT1 RT2 1. Francisco Guarner Spain Chair Y 2. Mary Ellen Sanders USA Co-chair Y 3. Rami Eliakim Israel 4. Richard Fedorak Canada 5. Alfred Gangl Austria 6. James Garisch South Africa 7. Pedro Kaufmann Uruguay 8. Tarkan Karakan Turkey 9. Aamir G. Khan Pakistan 10. Nayoung Kim South Korea 11. Juan Andres de Paula Argentina 12. Balakrishnan Ramakrishna India 13. Fergus Shanahan Ireland 14. Hania Szajewska Poland 15. Alan Thomson Canada 16. Dan Merenstein USA Invited expert 17. Seppo Salminen Finland Invited expert
- 49. ACKNOWLEDGMENTS VELLORE V.I. Mathan Selvi Krishnan AparnaVenkatraman S. Venkataraman N.S. Nanda Kumar R. Balamurugan S. Pugazhendhi S. Srikanth K. Jayakanthan K. Madhu Mohan Sandya Rani Kalpana P. NEW HAVEN Henry Binder Judy Cho BOSTON Joshua Korzenik PARIS J-F Desjeux Philippe Pochart Antonia Suau CLERMONT-FERRAND Isabelle Creveaux ICMR Broad Medical Research Program DBT The Wellcome Trust CSIR Indo-France Science Program Bill & Melinda Gates Foundation