Microbial dysbiosis and mortality during mechanical ventilation: a prospective observational study

Daphnée Lamarche; Jennie Johnstone; Nicole Zytaruk; France Clarke; Lori Hand; Dessi Loukov; Jake C Szamosi; Laura Rossi; Louis P Schenck; Chris P Verschoor; Ellen McDonald; Maureen O Meade; John C Marshall; Dawn M E Bowdish; Tim Karachi; Diane Heels-Ansdell; Deborah J Cook; Michael G Surette; PROSPECT Investigators; Canadian Critical Care Trials Group; Canadian Critical Care Translational Biology Group

doi:10.1186/s12931-018-0950-5

Microbial dysbiosis and mortality during mechanical ventilation: a prospective observational study

Respir Res. 2018 Dec 7;19(1):245. doi: 10.1186/s12931-018-0950-5.

Authors

Daphnée Lamarche^{1

2

3}, Jennie Johnstone^{4

5

6}, Nicole Zytaruk^{7

8}, France Clarke^{7

8}, Lori Hand^{8

9}, Dessi Loukov^{2

10}, Jake C Szamosi^{2

3

11}, Laura Rossi^{1

2

3}, Louis P Schenck^{1

2

3}, Chris P Verschoor⁸, Ellen McDonald^{8

11}, Maureen O Meade^{8

9

11}, John C Marshall^{12

13}, Dawn M E Bowdish^{2

10}, Tim Karachi^{9

11}, Diane Heels-Ansdell⁸, Deborah J Cook^{7

8

11}, Michael G Surette^{14

15

16

17}; PROSPECT Investigators; Canadian Critical Care Trials Group; Canadian Critical Care Translational Biology Group

Affiliations

¹ Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada.
² Institute for Infectious Disease Research, McMaster University, Hamilton, ON, Canada.
³ Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada.
⁴ Department of Medicine, University of Toronto, Toronto, ON, Canada.
⁵ Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.
⁶ Public Health Ontario, Toronto, ON, Canada.
⁷ St. Joseph's Healthcare, Hamilton, ON, Canada.
⁸ Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, Canada.
⁹ Hamilton Health Sciences, Hamilton, ON, Canada.
¹⁰ Department of Pathology and Molecular Medicine, Hamilton, ON, Canada.
¹¹ Department of Medicine, McMaster University, Health Sciences Bldg, 3N8F, 1280 Main Street West, Hamilton, ON, L8S 4K1, Canada.
¹² Department of Surgery, University of Toronto, Toronto, ON, Canada.
¹³ Interdepartmental Division of Critical Care, University of Toronto, Toronto, ON, Canada.
¹⁴ Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada. Surette@mcmaster.ca.
¹⁵ Institute for Infectious Disease Research, McMaster University, Hamilton, ON, Canada. Surette@mcmaster.ca.
¹⁶ Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada. Surette@mcmaster.ca.
¹⁷ Department of Medicine, McMaster University, Health Sciences Bldg, 3N8F, 1280 Main Street West, Hamilton, ON, L8S 4K1, Canada. Surette@mcmaster.ca.

Abstract

Background: Host-associated microbial communities have important roles in tissue homeostasis and overall health. Severe perturbations can occur within these microbial communities during critical illness due to underlying diseases and clinical interventions, potentially influencing patient outcomes. We sought to profile the microbial composition of critically ill mechanically ventilated patients, and to determine whether microbial diversity is associated with illness severity and mortality.

Methods: We conducted a prospective, observational study of mechanically ventilated critically ill patients with a high incidence of pneumonia in 2 intensive care units (ICUs) in Hamilton, Canada, nested within a randomized trial for the prevention of healthcare-associated infections. The microbial profiles of specimens from 3 anatomical sites (respiratory, and upper and lower gastrointestinal tracts) were characterized using 16S ribosomal RNA gene sequencing.

Results: We collected 65 specimens from 34 ICU patients enrolled in the trial (29 endotracheal aspirates, 26 gastric aspirates and 10 stool specimens). Specimens were collected at a median time of 3 days (lower respiratory tract and gastric aspirates; interquartile range [IQR] 2-4) and 6 days (stool; IQR 4.25-6.75) following ICU admission. We observed a loss of biogeographical distinction between the lower respiratory tract and gastrointestinal tract microbiota during critical illness. Moreover, microbial diversity in the respiratory tract was inversely correlated with APACHE II score (r = - 0.46, p = 0.013) and was associated with hospital mortality (Median Shannon index: Discharged alive; 1.964 vs. Deceased; 1.348, p = 0.045).

Conclusions: The composition of the host-associated microbial communities is severely perturbed during critical illness. Reduced microbial diversity reflects high illness severity and is associated with mortality. Microbial diversity may be a biomarker of prognostic value in mechanically ventilated patients.

Trial registration: ClinicalTrials.gov ID NCT01782755 . Registered February 4 2013.

Keywords: Critical illness; Gastrointestinal tract microbiota; Microbial diversity; Microbiome; Respiratory tract microbiota.

Publication types

Observational Study
Randomized Controlled Trial

MeSH terms

Aged
Critical Illness / epidemiology
Critical Illness / therapy
Dysbiosis / etiology
Dysbiosis / microbiology*
Dysbiosis / mortality*
Female
Humans
Intensive Care Units / trends
Male
Microbiological Phenomena*
Middle Aged
Pilot Projects
Prospective Studies
Respiration, Artificial / adverse effects*
Respiration, Artificial / mortality*

Associated data

ClinicalTrials.gov/NCT01782755