the gut in critical illness: a perspective in five acts by prof. john marshall
TRANSCRIPT
The Gut Hypothesis of Acute Illness:
A Subjective History in Five Acts
John C. Marshall MD FRCSCCICM Annual Meeting
Sydney, Australia May 26, 2017
University of TorontoSt. Michael’s Hospital
“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.”
Mo
rtality
(P
erc
en
t)
0
20
40
60
80
100Control
Germ-free
Klebsiella M. S. aureus Endotoxin
tuberculosis
- J Exp Med 111:407, 1960
“The Gastrointestinal Tract:
The Motor of Multiple Organ Failure”
- Ann Surg 206:427, 1987
John Border
Jonathan Meakins
Act 4 North America 20thc.
Edwin Deitch
Bacterial Translocation
• Sepsis• Trauma• Endotoxemia• Burns• Liver injury• Parenteral nutrition• Altered flora• Cardiac arrest• Antibiotics
Carole Wells
Per cent of Patients Infected
0 10 20 30 40 50 60
MO
F Sc
ore
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
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
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
Selective Decontamination of the Digestive Tract (SDD)
• Topical tobramycin, polymyxin, amphotericin B
• 3 – 4 days systemic cephalosporin
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
Impact of Indigenous Flora on
Intestinal Gene Expression
Zebrafish 212 genesRawls, PNAS 101:4596, 2004
Mouse 267 genesMutch, Physiol Genomics 2004
HIF-1α from Ischemic Gut
Induces the Virulence Factor
PA-I in Pseudomonas
- Patel, AJP Gastrointest Liver Physiol 292:G134, 2007
“… 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
These our actors,As I foretold you, were all spirits andAre 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 dissolveAnd, like this insubstantial pageant faded,Leave not a rack behind. We are such stuffAs dreams are made on, and our little lifeIs rounded with a sleep.
Thank you!!The Tempest Act IV Scene i