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The gut in critical Illness: A perspective in five acts by Prof. John Marshall

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The gut in critical Illness: A perspective in five acts

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The gut in critical Illness: A perspective in five acts by Prof. John Marshall

  1. 1. The Gut Hypothesis of Acute Illness: A Subjective History in Five Acts John C. Marshall MD FRCSC CICM Annual Meeting Sydney, Australia May 26, 2017 University of TorontoSt. Michael’s Hospital
  2. 2. Dora Mavor Moore 1888 - 1979
  3. 3. Prologue: The emergence of multicellular organisms
  4. 4. Act 1: The Ancient Mediterranean Ebers Papyrus 1550 BCEUkhedu
  5. 5. Asclepion Of Kos Hippocrates 460-370 BCE
  6. 6. Act 2 19th Century Europe Louis Pasteur 1822 - 1895 Eli Metchnikoff 1845 - 1916
  7. 7. “When faecal matter is allowed to remain in the intestine, certain products are absorbed by the organism, and produce poisoning…. While most microbes are confined within the walls of the alimentary canal, the soluble excretions produced by them pass through into the lymph and blood.”
  8. 8. Sir William Arbuthnot Lane
  9. 9. Act 3 USA; mid-20th Century Jacob Fine “The intestinal factor in shock”
  10. 10. Mortality(Percent) 0 20 40 60 80 100 Control Germ-free Klebsiella M. S. aureus Endotoxin tuberculosis - J Exp Med 111:407, 1960
  11. 11. The indigenous flora – particularly anerobes – protect against infection.
  12. 12. Endotoxin (Lipopolysaccharide)
  13. 13. “The Gastrointestinal Tract: The Motor of Multiple Organ Failure” - Ann Surg 206:427, 1987 John Border Jonathan Meakins Act 4 North America 20thc.
  14. 14. Edwin Deitch Bacterial Translocation • Sepsis • Trauma • Endotoxemia • Burns • Liver injury • Parenteral nutrition • Altered flora • Cardiac arrest • Antibiotics Carole Wells
  15. 15. Per cent of Patients Infected 0 10 20 30 40 50 60 MOFScore 1 - 2 3 - 4 5 - 8 9 - 16 Pseudomonas Candida S. epidermidis 0 Association of Organ Failure with Nosocomial Infection - Marshall J Hosp Infect 19:7, 1991
  16. 16. Organism # Patients Mean CFU/ml Candida 19 4.3  1.6 S. fecalis 12 6.8  0.8 Pseudomonas 10 6.9  1.1 S. epidermidis 10 5.7  1.6 E. coli 7 6.2  1.6 - Ann Surg 218:111, 1993
  17. 17. INFECTION RATE (%) Organism Colonized Not Colonized p. Pseudomonas 90 19 <0.001 S. epidermidis 80 26 <0.01 Candida 79 36 <0.01 Enterococcus 50 38 N.S. Proximal Gut Colonization and Systemic Infection - Ann Surg 218:111, 1993
  18. 18. Gut Flora Can Modulate Systemic Immunity - J Surg Res 55:14, 1993
  19. 19. Selective Decontamination of the Digestive Tract (SDD) • Topical tobramycin, polymyxin, amphotericin B • 3 – 4 days systemic cephalosporin
  20. 20. • Cluster RCT 100 centres; 25,000 patients • Ecology study • Cost-effectiveness study
  21. 21. Act 5 Global 21st C. The Microbiome The Global Biomass • 560 Bn tons carbon • Sub-sea floor 2.9 X 1029 organisms • ?1 billion species
  22. 22. Oral Cavity: 700 species Skin: 1000 species Gastrointestinal Tract: 5000 species
  23. 23. Impact of Indigenous Flora on Intestinal Gene Expression Zebrafish 212 genes Rawls, PNAS 101:4596, 2004 Mouse 267 genes Mutch, Physiol Genomics 2004
  24. 24. Promotion of Intestinal Angiogenesis by B. thetaiotaomicron - Stappenbeck, PNAS 99:15451, 2002
  25. 25. The Microbiome in the Pathogenesis of Disease --Nature 535:65, 2016
  26. 26. Dysbiosis of the Microbiome in Sepsis mSphere. 2016 Jul-Aug; 1(4): e00199-16
  27. 27. HIF-1α from Ischemic Gut Induces the Virulence Factor PA-I in Pseudomonas - Patel, AJP Gastrointest Liver Physiol 292:G134, 2007
  28. 28. Probiotics Reduce Rates of VAP
  29. 29. - Crit Care. 2016 Oct 18;20(1):332
  30. 30. “… one of the most important changes we can make is to supercede the 20th-century metaphor of war for describing the relationship between people and infectious agents. A more ecologically informed metaphor, which includes the germs’-eye view of infection, might be more fruitful … they are equally part of the superorganism genome with which we engage the rest of the biosphere.” - Joshua Lederberg, Science 288:287, 2000
  31. 31. Epilogue: Beyond the Microbiome
  32. 32. These our actors, As I foretold you, were all spirits and Are melted into air, into thin air: And, like the baseless fabric of this vision, The cloud-capp'd towers, the gorgeous palaces, The solemn temples, the great globe itself, Ye all which it inherit, shall dissolve And, like this insubstantial pageant faded, Leave not a rack behind. We are such stuff As dreams are made on, and our little life Is rounded with a sleep. Thank you!! The Tempest Act IV Scene i

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