Abstract

Aim: Emerging evidence suggests intestinal dysbiosis may impact systemic immune response; however, there is a paucity of data connecting dysbiosis of the lung microbiome to host immunity in critical illness. To address this knowledge gap, we performed a prospective longitudinal multi-omics analysis of the systemic immune landscape and lung microbiota composition in critically ill patients.

Methods: Whole blood and sputum samples were collected from patients admitted to the Foothills Medical Centre ICU over the first week of admission. 16S rRNA amplicon sequencing was performed on sputum to evaluate microbiota composition. The systemic immune landscape was characterized by single-cell mass cytometry and inflammatory mediators were quantified using a multiplexed assay.

Results: Preliminary results show significant variation in the lung microbiota of patients at time of admission. Community analysis identified partitioning of microbiota composition driven by presence of anaerobic bacteria such as Prevotella and Veillonella, with Prevotella identified as a keystone ventilator-associated pneumonia (VAP) microbe. Moreover, patients with a high relative abundance of anaerobes at time of admission had significantly reduced 30-day VAP-free survival (HR 2.66, 95% CI 1.08 ? 6.5; p=0.033), coupled with distinct shifts in the monocyte and neutrophil compartments over the first 72 hours of admission.

Conclusions: Our preliminary data suggests characterization of the lung microbiota at time of admission allows early prognostication of clinical outcomes and may represent a novel biomarker in evaluation and management of critically ill patients.