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Microbial dysbiosis and mortality during mechanical ventilation: a prospective observational study
Authors: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
Affiliation:1.Department of Biochemistry and Biomedical Sciences,McMaster University,Hamilton,Canada;2.Institute for Infectious Disease Research,McMaster University,Hamilton,Canada;3.Farncombe Family Digestive Health Research Institute,McMaster University,Hamilton,Canada;4.Department of Medicine,University of Toronto,Toronto,Canada;5.Dalla Lana School of Public Health,University of Toronto,Toronto,Canada;6.Public Health Ontario,Toronto,Canada;7.St. Joseph’s Healthcare,Hamilton,Canada;8.Department of Health Research Methods, Evidence and Impact,McMaster University,Hamilton,Canada;9.Hamilton Health Sciences,Hamilton,Canada;10.Department of Pathology and Molecular Medicine,Hamilton,Canada;11.Department of Medicine,McMaster University,Hamilton,Canada;12.Department of Surgery,University of Toronto,Toronto,Canada;13.Interdepartmental Division of Critical Care,University of Toronto,Toronto,Canada
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:
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