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

• Main 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, for the PROSPECT Investigators, Canadian Critical Care Trials Group, Canadian Critical Care Translational Biology Group
• Format: Article
• Language: English
• Published: BMC 2018-12-01
• Series: Respiratory Research
• Subjects: Microbiome; Critical illness; Microbial diversity; Respiratory tract microbiota; Gastrointestinal tract microbiota
• Online Access: http://link.springer.com/article/10.1186/s12931-018-0950-5

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.