The Gastrointestinal Tract in MODS:

A History

John C. Marshall MD FRCSCCritical Care Canada Forum

Toronto, Ontario

November 12, 2019University of TorontoSt. Michael’s Hospital

Prologue:

The emergence of multicellular organisms

The Ancient Mediterranean

Ebers Papyrus1550 BCEUkhedu

19th Century Europe

Louis Pasteur1822 - 1895

Eli Metchnikoff1845 - 1916

“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.”

Sir William Arbuthnot Lane

USA; mid-20th Century

Jacob Fine

“The intestinal factor in shock”

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

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

Global 21st C. The Microbiome

• 560 Bn tons carbon

• Sub-sea floor 2.9 X 1029 organisms

• ?1 billion species

Oral Cavity:700 species

Skin: 1000 species

Gastrointestinal Tract:

5000 species

Promotion of Intestinal Angiogenesis by

B. thetaiotaomicron

- Stappenbeck, PNAS 99:15451, 2002

Dysbiosis of the Microbiome

in Sepsis

mSphere. 2016 Jul-Aug; 1(4): e00199-16

Common Organisms from Hospital Water

Pipes

• Klebsiella• Acinetobacter• Pseudomonas• Legionella

S. epidermidis E. coli

S. aureus Pseudomonas

Enterococcus Klebsiella

Enterobacter

Acinetobacter

B. fragilis Morganella

C. difficile Haemophilus

Proteus

Candida

Thrive in the hospital water supply

• Hospital as a reservoir for nosocomial infection

- J Infect Dis 174:1279, 1996

• Multinational Cluster RCT

• Ecology study

• Cost-effectiveness study

- Gut 66:569, 2017

“… 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

- Alex Colville 1920 - 2013

Thank you!