Dysbiosis in the intensive care unit: Microbiome science coming to the bedside

Abstract

Complex microbial communities within the human body, constituting the microbiome, have a broad impact on human health and disease. A growing body of research now examines the role of the microbiome in patients with critical illness, such as sepsis and acute respiratory failure. In this article, we provide an introduction to microbiome concepts and terminology and we systematically review the current evidence base of the critical-illness microbiome, including 51 studies in animal models and pediatric and adult critically ill patients. We further examine how this emerging scientific discipline may transform the way we manage infectious and inflammatory diseases in intensive care units. The evolving molecular, culture-independent techniques offer the ability to study microbial communities in unprecedented depth and detail, and in the short-term, may enable us to diagnose and treat infections in critical care more precisely and effectively. Longer term, these tools may also give us insights in the underlying pathophysiology of critical illness and reveal previously unsuspected targets for innovative, microbiome-targeted therapeutics. We finally propose a roadmap for future studies in the field for transforming critical care from its current isolated focus on the host to a more personalized paradigm addressing both human and microbial contributions to critical illness.

Keywords: Acute respiratory distress syndrome; Acute respiratory failure; Dysbiosis; Microbiome; Microbiota; Sepsis.

Figure 1

Factors that may alter the microbiome in the ICU (shown in red boxes) and references of reviewed microbiome studies according to body site sampled and study subjects (animal, adult or pediatric patients) (shown in blue boxes). Reference numbers (prefaced by “S”) correspond to the reference list provided in the Online Data Supplement. References for studies in sepsis are presented in black font and for studies in acute respiratory failure in red font. Abbreviations: ETT: endotracheal tube; PPIs: proton-pump inhibitors; H2B: histamine-2 receptor blockers; TPN: total parenteral nutrition; PPV: positive pressure ventilation; VILI: ventilator-induced lung injury; Peds: pediatrics

Figure 2

Overview of therapeutic strategies for targeted microbiome manipulations. A. Strategies targeting microbiome structure include commensal enrichment approaches (bacterial transplantation, probiotics or prebiotics) and pathogen suppression approaches (with bioengineered commensals designed to outperform pathogens or bacteriophage transfection). B. Strategies targeting microbiome function include direct bacterial enzyme inhibition, isolation of bacteriocins as naturally occurring antibiotics or isolation of small molecule agonists of host receptors (postbiotics) to emulate the beneficial effects of commensal microbes. Abbreviations: SCFA: short-chain fatty acids.